Background:The aim of the study was to explore the ecological diversity of wild birds in Siberia, which are the natural reservoir of avian influenza virus(AIV).Methods:Cloacal swabs and intestinal fragments were colle...Background:The aim of the study was to explore the ecological diversity of wild birds in Siberia, which are the natural reservoir of avian influenza virus(AIV).Methods:Cloacal swabs and intestinal fragments were collected from wild migratory birds from 2007-2014. Isolated viruses were grown in the allantoic cavity of embryonated chicken eggs. The presence of virus was determined using hemagglutination assays. Primary identification and subtyping of influenza viruses was confirmed by RT-PCR.Results:A total of 2300 samples obtained from wild migratory birds of 8 orders were collected and tested. Influenza was detected in 185 birds of 3 orders. Species of family Anatidae(order Anseriformes) such as European Teal(Anas crecca), Garganey Teal(A. querquedula), and Shoveler(A. clypeata) play the main role in AIV circulation in the south of Western Siberia. The proportion of viral carriers among waterfowl ranged from 5.6 to 20% in 2007-2014. The order Charadriiformes had lower virus isolation rates of not more than 1.4%.Conclusions:Wild migratory waterfowl of orders Anseriformes and Charadriiformes are the main reservoir of AIV in the south of Western Siberia. This area plays a key role in persistence, evolution, and geographical distribution of avian influenza.展开更多
Severe acute respiratory syndrome coronavirus 2(SARSCo V-2)infection can result in more severe syndromes and poorer outcomes in patients with diabetes and obesity.However,the precise mechanisms responsible for the com...Severe acute respiratory syndrome coronavirus 2(SARSCo V-2)infection can result in more severe syndromes and poorer outcomes in patients with diabetes and obesity.However,the precise mechanisms responsible for the combined impact of coronavirus disease 2019(COVID-19)and diabetes have not yet been elucidated,and effective treatment options for SARS-Co V-2-infected diabetic patients remain limited.To investigate the disease pathogenesis,K18-h ACE2 transgenic(h ACE2^(Tg))mice with a leptin receptor deficiency(h ACE2-Lepr^(-/-))and high-fat diet(h ACE2-HFD)background were generated.The two mouse models were intranasally infected with a 5×10^(5) median tissue culture infectious dose(TCID_(50))of SARSCo V-2,with serum and lung tissue samples collected at 3days post-infection.The h ACE2-Lepr^(-/-)mice were then administered a combination of low-molecular-weight heparin(LMWH)(1 mg/kg or 5 mg/kg)and insulin via subcutaneous injection prior to intranasal infection with1×10^(4) TCID_(50)of SARS-Co V-2.Daily drug administration continued until the euthanasia of the mice.Analyses of viral RNA loads,histopathological changes in lung tissue,and inflammation factors were conducted.Results demonstrated similar SARS-Co V-2 susceptibility in h ACE2^(Tg)mice under both lean(chow diet)and obese(HFD)conditions.However,compared to the h ACE2-Lepr^(+/+)mice,h ACE2-Lepr^(-/-)mice exhibited more severe lung injury,enhanced expression of inflammatory cytokines and hypoxia-inducible factor-1α(HIF-1α),and increased apoptosis.Moreover,combined LMWH and insulin treatment effectively reduced disease progression and severity,attenuated lung pathological changes,and mitigated inflammatory responses.In conclusion,preexisting diabetes can lead to more severe lung damage upon SARS-Co V-2 infection,and LMWH may be a valuable therapeutic approach for managing COVID-19patients with diabetes.展开更多
Studies on influenza virus by Chinese Academy of Sciences(CAS)could be traced back as early as 2005 by the CAS Key Laboratory of Pathogenic Microbiology and Immunology(CASPMI),who discovered that Qinghai-like Clade 2....Studies on influenza virus by Chinese Academy of Sciences(CAS)could be traced back as early as 2005 by the CAS Key Laboratory of Pathogenic Microbiology and Immunology(CASPMI),who discovered that Qinghai-like Clade 2.2H5N1 subtype highly pathogenic avian influenza virus(HPAIV)first caused severe outbreak in wild birds in Qinghai Lake(Liu et al.,2005).展开更多
The ongoing pandemic of coronavirus disease 2019 (COVID-19), caused by infection with human coronavirus 2019 (HCoV-19/SARS-CoV-2/2019-nCoV), is a global threat to the human population. Here, we briefly summarize the a...The ongoing pandemic of coronavirus disease 2019 (COVID-19), caused by infection with human coronavirus 2019 (HCoV-19/SARS-CoV-2/2019-nCoV), is a global threat to the human population. Here, we briefly summarize the available data for the zoonotic origins of HCoV-19, with reference to the other two epidemics of highly virulent coronaviruses, SARSCoV and MERS-CoV, which cause severe pneumonia in humans. We propose to intensify future efforts for tracing the origins of HCoV-19, which is a very important scientific question for the control and prevention of the pandemic.展开更多
Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection often leads to pulmonary complications.Cardiovascular sequelae,including myocarditis and heart failure,have also been reported.Here,the study presen...Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection often leads to pulmonary complications.Cardiovascular sequelae,including myocarditis and heart failure,have also been reported.Here,the study presents two fulminant myocarditis cases infected by SARS-CoV-2 exhibiting remarkable elevation of cardiac biomarkers without significant pulmonary injury,as determined by imaging examinations.Immunohistochemical staining reveals the viral antigen within cardiomyocytes,indicating that SARSCoV-2 could directly infect the myocardium.The full viral genomes from respiratory,anal,and myocardial specimens are obtained via next-generation sequencing.Phylogenetic analyses of the whole genome and spike gene indicate that viruses in the myocardium/pericardial effusion and anal swabs are closely related and cluster together yet diverge from those in the respiratory samples.In addition,unique mutations are found in the anal/myocardial strains compared to the respiratory strains,suggesting tissue-specific virus mutation and adaptation.These findings indicate genetically distinct SARS-CoV-2 variants have infiltrated and disseminated within myocardial tissues,independent of pulmonary injury,and point to different infection routes between the myocardium and respiratory tract,with myocardial infections potentially arising from intestinal infection.These findings highlight the potential for systemic SARS-CoV-2 infection and the importance of a thorough multi-organ assessment in patients for a comprehensive understanding of thepathogenesisof COVID-19.展开更多
Human infections with influenza H7 subtypes, such as H7N9, have raised concerns worldwide. Here, we report a human infection with a novel influenza A(H7N4) virus. A 68 years-old woman with cardiovascular and cholecyst...Human infections with influenza H7 subtypes, such as H7N9, have raised concerns worldwide. Here, we report a human infection with a novel influenza A(H7N4) virus. A 68 years-old woman with cardiovascular and cholecystic comorbidities developed rapidly progressed pneumonia with influenza-like-illness as initial symptom, recovered after 23 days-hospitalization including 8 days in ICU. Laboratory indicators for liver and blood coagulation dysfunction were observed. Oseltamivir phosphate, glucocorticoids and antibiotics were jointly implemented, with nasal catheterization of oxygen inhalation for this patient.We obtained the medical records and collected serial respiratory and blood specimens from her. We collected throat, cloacal and/or feces samples of poultry and wild birds from the patient's backyard, neighborhood, local live poultry markets(LPMs) and the nearest lake. All close contacts of the patient were followed up and sampled with throat swabs and sera. Influenza viruses and other respiratory pathogens were tested by real-time RT-PCR, viral culturing and/or sequencing for human respiratory and bird samples. Micro-neutralizing assay was performed for sera. A novel reassortant wild bird-origin H7N4 virus is identified from the patient and her backyard poultry(chickens and ducks) by sequencing, which is distinct from previously-reported avian H7N4 and H7N9 viruses. At least four folds increase of neutralizing antibodies to H7N4 was detected in her convalescent sera. No samples from close contacts, wild birds or other poultry were tested positive for H7N4 by real-time RT-PCR.展开更多
Dear Editor,Avian influenza viruses (AIVs) have posed a serious threat to poultry production and public health. To date, more than fourteen AIV subtypes that are able to infect human beings have been documented. Also,...Dear Editor,Avian influenza viruses (AIVs) have posed a serious threat to poultry production and public health. To date, more than fourteen AIV subtypes that are able to infect human beings have been documented. Also, it is suggested that new subtypes may be reported in the future, owing to the migration of wild birds and live poultry transportation (Gao, 2018).Poultry may act as a potential incubator for novel subtypes of avian influenza virus (Bi et al., 2016a; Bi et al., 2016b; Liu et al., 2014a; Su et al., 2017). Up to date, the H7N9 AIV emerged in February 2013 has caused 1,567 human cases,with a fatality rate of 39.2%(http://www.who.int/influenza/展开更多
A novel Clade 2.3.2.1c H5N1 reassortant virus caused several outbreaks in wild birds in some regions of China from late 2014 to 2015.Based on the genetic and phylogenetic analyses,the viruses possess a stable gene con...A novel Clade 2.3.2.1c H5N1 reassortant virus caused several outbreaks in wild birds in some regions of China from late 2014 to 2015.Based on the genetic and phylogenetic analyses,the viruses possess a stable gene constellation with a Clade 2.3.2.1c HA,a H9N2-derived PB2 gene and the other six genes of Asian H5N1-origin.The Clade 2.3.2.1c H5N1 reassortants displayed a high genetic relationship to a human H5N1 strain(A/Alberta/01/2014).Further analysis showed that similar viruses have been circulating in wild birds in China,Russia,Dubai(Western Asia),Bulgaria and Romania(Europe),as well as domestic poultry in some regions of Africa.The affected areas include the Central Asian,East Asian-Australasian,West Asian-East African,and Black Sea/Mediterranean flyways.These results show that the novel Clade 2.3.2.1c reassortant viruses are circulating worldwide and may have gained a selective advantage in migratory birds,thus posing a serious threat to wild birds and potentially humans.展开更多
Dear Editor Marine mammals are widely distributed and can be found almost in all coastal waters and coastlines around the world.The interface areas between marine and terrestrial environments provide natural habitats ...Dear Editor Marine mammals are widely distributed and can be found almost in all coastal waters and coastlines around the world.The interface areas between marine and terrestrial environments provide natural habitats for aquatic and semiaquatic mammals as well as for reservoir species of avian influenza viruses (AIV)(Runstadler et al.2013).展开更多
Innate immunity plays critical antiviral roles. The highly virulent avian influenza viruses (AIVs) H5N1, H7N9, and H5N6 can betterescape host innate immune responses than the less virulent seasonal H1N1 virus. Here, w...Innate immunity plays critical antiviral roles. The highly virulent avian influenza viruses (AIVs) H5N1, H7N9, and H5N6 can betterescape host innate immune responses than the less virulent seasonal H1N1 virus. Here, we report a mechanism by whichtranscriptional readthrough (TRT)-mediated suppression of innate immunity occurs post AIV infection. By using cell lines, mouselungs, and patient PBMCs, we showed that genes on the complementary strand (“trans” genes) influenced by TRT were involved inthe disruption of host antiviral responses during AIV infection. The trans-TRT enhanced viral lethality, and TRT abolishmentincreased cell viability and STAT1/2 expression. The viral NS1 protein directly bound to SSU72, and degradation of SSU72 inducedTRT. SSU72 overexpression reduced TRT and alleviated mouse lung injury. Our results suggest that AIVs infection induce TRT byreducing SSU72 expression, thereby impairing host immune responses, a molecular mechanism acting through the NS1-SSU72-trans-TRT-STAT1/2 axis. Thus, restoration of SSU72 expression might be a potential strategy for preventing AIV pandemics.展开更多
Since the 20th century,humans have lived through five pandemics caused by influenza A viruses(IAVs)(H1N1/1918,H2N2/1957,H3N2/1968,and H1N1/2009)and the coronavirus(CoV)severe acute respiratory syndrome coronavirus 2(S...Since the 20th century,humans have lived through five pandemics caused by influenza A viruses(IAVs)(H1N1/1918,H2N2/1957,H3N2/1968,and H1N1/2009)and the coronavirus(CoV)severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).IAVs and CoVs both have broad host ranges and share multiple hosts.Virus co-circulation and even co-infections facilitate genetic reassortment among IAVs and recombination among CoVs,further altering virus evolution dynamics and generating novel variants with increased cross-species transmission risk.Moreover,SARS-CoV-2 may maintain longterm circulation in humans as seasonal IAVs.Co-existence and co-infection of both viruses in humans could alter disease transmission patterns and aggravate disease burden.Herein,we demonstrate how virus-host ecology correlates with the co-existence and co-infection of IAVs and/or CoVs,further affecting virus evolution and disease dynamics and burden,calling for active virus surveillance and countermeasures for future public health challenges.展开更多
Dear Editor,Akabane disease is an arthropod-borne viral disease caused by the Akabane virus(AKAV)that can affect cattle,sheep,and goats.Inapparent infections in adults can lead months later to abortions,stillbirths,co...Dear Editor,Akabane disease is an arthropod-borne viral disease caused by the Akabane virus(AKAV)that can affect cattle,sheep,and goats.Inapparent infections in adults can lead months later to abortions,stillbirths,congenital defects,and death in newborns(Kurogi et al.,1976).Wild ruminants can also be affected,but abnormalities of the offspring in these species have not been reported.One report suggests that this virus can also cause clinical signs in pigs(Yanase et al.,2018).展开更多
Influenza is one of the oldest infectious diseases affecting humans. Every influenza pandemic in history has ended with disastrous outcomes regarding public health and the social economy. This year marks the 100th ann...Influenza is one of the oldest infectious diseases affecting humans. Every influenza pandemic in history has ended with disastrous outcomes regarding public health and the social economy. This year marks the 100th anniversary of the Spanish flu (H1N1) outbreak of 1918, which is recognized as the most lethal natural event in recent history.展开更多
The Zika virus(ZIKV) is an arbovirus that has spread rapidly worldwide within recent times. There is accumulating evidence that associates ZIKV infections with Guillain-Barré Syndrome(GBS) and microcephaly in hum...The Zika virus(ZIKV) is an arbovirus that has spread rapidly worldwide within recent times. There is accumulating evidence that associates ZIKV infections with Guillain-Barré Syndrome(GBS) and microcephaly in humans. The ZIKV is genetically diverse and can be separated into Asian and African lineages. A rapid, sensitive, and specific assay is needed for the detection of ZIKV across various pandemic regions. So far, the available primers and probes do not cover the genetic diversity and geographic distribution of all ZIKV strains. To this end, we have developed a one-step quantitative reverse transcription polymerase chain reaction(qRT-PCR) assay based on conserved sequences in the ZIKV envelope(E) gene. The detection limit of the assay was determined to be five RNA transcript copies and 2.94 × 10^(–3) 50% tissue culture infectious doses(TCID50) of live ZIKV per reaction. The assay was highly specific and able to detect five different ZIKV strains covering the Asian and African lineages without nonspecific amplification, when tested against other flaviviruses. The assay was also successful in testing for ZIKV in clinical samples. Our assay represents an improvement over the current methods available for the detection ZIKV and would be valuable as a diagnostic tool in various pandemic regions.展开更多
The ongoing pandemic of coronavirus disease 2019(COVID-19)caused by a novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2,also named as 2019-nCoV or HCoV-19)poses an unprecedented threat to public health(...The ongoing pandemic of coronavirus disease 2019(COVID-19)caused by a novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2,also named as 2019-nCoV or HCoV-19)poses an unprecedented threat to public health(Zhu et al.,2020;Wang et al.,2020;Jiang et al.,2020).The novel HCoV-19 virus has rapidly spread into multiple countries across the world since it was first reported in December 2019.The World Health Organization(WHO)declared COVID-19 as a pandemic on 11th March 2020.As of 4th July,over 10 million confirmed COVID-19 cases have been reported in over 200 countries/regions with more than 0.5 million deaths,including 85,287 documented cases and 4,648 deaths in China(WHO,2020a).展开更多
Dear Editor,In recent years,the incidence of human infections caused by emerging or re-emerging pathogens has rapidly increased.Diseases that were once regional now have the ability to spread globally in a short amoun...Dear Editor,In recent years,the incidence of human infections caused by emerging or re-emerging pathogens has rapidly increased.Diseases that were once regional now have the ability to spread globally in a short amount of time and pose a wider threat to public health(Weaver et al.2018).Yellow fever virus(YFV,family Flaviviridae,genus Flavivirus)is a mosquito-borne flavivirus that causes yellow fever in humans and has been endemic in Africa and Latin America for many years(Domingo et al.2018).展开更多
Dear Editor,The ongoing SARS-CoV-2 pandemic has lasted for 2 years,causing a severe global impact on social development.With widespread vaccinations,the number of new infections has dropped significantly,but with the ...Dear Editor,The ongoing SARS-CoV-2 pandemic has lasted for 2 years,causing a severe global impact on social development.With widespread vaccinations,the number of new infections has dropped significantly,but with the emergence of diverse novel variants of concern(VOCs)and variants of interest(VOIs),there has been a second or third epidemic wave in many countries.展开更多
Dear Editor,Astroviruses(AstVs)are non-enveloped,single-stranded RNA viruses with a diameter of approximately 35 nm(Madeley and Cosgrove 1975).The genomes of AstVs range in size from 6.8 to 7.9 kb(De Benedictis et al....Dear Editor,Astroviruses(AstVs)are non-enveloped,single-stranded RNA viruses with a diameter of approximately 35 nm(Madeley and Cosgrove 1975).The genomes of AstVs range in size from 6.8 to 7.9 kb(De Benedictis et al.2011),consisting of a 5'-untranslated region(UTR),three open reading frames(ORFs),a 3'-UTR,and a poly-adenylated(polyA)tail(Pantin-Jackwood et al.2006).In 1975,AstVs were first discovered in faeces of infants(Madeley and Cosgrove 1975).Until now,a variety of animal species,including cows,sheep,pigs,dogs,deer,rats,bats,chickens,ducks,turkeys,sea lions and seals have been reported to be infected with AstVs(Tzipori et al.1981;Cattoli et al.2007;Chu et al.2008,2010;Atkins et al.2009;Toffan et al.2009;Rivera et al.2010;Guix et al.2013;Kang et al.2012;Reuter et al.2012a,2012b;Li et al.2021).Currently,AstVs comprise two genera,Mamastrovirus(MAstV)and Avastrovirus(AAstV).Herein,we describe three novel AAstVs identified from dead crow tissues.To our knowledge,this is the first report for identification of AstVs in crows.展开更多
Emerging SARS-CoV-2 variants are the most serious problem for COVID-19 prophylaxis and treatment.To determine whether the SARS-CoV-2 vaccine strain should be updated following variant emergence like seasonal flu vacci...Emerging SARS-CoV-2 variants are the most serious problem for COVID-19 prophylaxis and treatment.To determine whether the SARS-CoV-2 vaccine strain should be updated following variant emergence like seasonal flu vaccine,the changed degree on antigenicity of SARS-CoV-2 variants and H3N2 flu vaccine strains was compared.The neutralization activities of Alpha,Beta and Gamma variants’spike protein-immunized sera were analysed against the eight current epidemic variants and 20 possible variants combining the top 10 prevalent RBD mutations based on the Delta variant,which were constructed using pseudotyped viruses.Meanwhile,the neutralization activities of convalescent sera and current inactivated and recombinant protein vaccine-elicited sera were also examined against all possible Delta variants.Eight HA protein-expressing DNAs elicited-animal sera were also tested against eight pseudotyped viruses of H3N2 flu vaccine strains from 2011–2019.Our results indicate that the antigenicity changes of possible Delta variants were mostly within four folds,whereas the antigenicity changes among different H3N2 vaccine strains were approximately 10–100-fold.Structural analysis of the antigenic characterization of the SARS-CoV-2 and H3N2 mutations supports the neutralization results.This study indicates that the antigenicity changes of the current SARS-CoV-2 may not be sufficient to require replacement of the current vaccine strain.展开更多
The outbreak of severe acute respiratory syndrome coronavirus 2(SARSCoV-2)has developed into an unprecedented global pandemic.Nucleoside analogs,such as Remdesivir and Favipiravir,can serve as the firstline broad-spec...The outbreak of severe acute respiratory syndrome coronavirus 2(SARSCoV-2)has developed into an unprecedented global pandemic.Nucleoside analogs,such as Remdesivir and Favipiravir,can serve as the firstline broad-spectrum antiviral drugs by targeting the viral polymerases.However,the underlying mechanisms for the antiviral efficacies of these drugs are far from well understood.Here,we reveal that Favipiravir,as a pyrazine derivative,could be incorporated into the viral RNA products by mimicking both adenine and guanine nucleotides.This drug thus inhibits viral replication mainly by inducing mutations in progeny RNAs,different from Remdesivir or other RNA-terminating nucleoside analogs that impair the elongation of RNA products.We further determined the cryo-EM structure of Favipiravir bound to the replicating polymerase complex of SARSCoV-2 in the pre-catalytic state.This structure provides a missing snapshot for visualizing the catalysis dynamics of coronavirus polymerase,and reveals an unexpected base-pairing pattern between Favipiravir and pyrimidine residues that may explain its capacity for mimicking both adenine and guanine nucleotides.These findings shed light on the mechanism of coronavirus polymerase catalysis and provide a rational basis for developing antiviral drugs to combat the SARS-CoV-2 pandemic.展开更多
文摘Background:The aim of the study was to explore the ecological diversity of wild birds in Siberia, which are the natural reservoir of avian influenza virus(AIV).Methods:Cloacal swabs and intestinal fragments were collected from wild migratory birds from 2007-2014. Isolated viruses were grown in the allantoic cavity of embryonated chicken eggs. The presence of virus was determined using hemagglutination assays. Primary identification and subtyping of influenza viruses was confirmed by RT-PCR.Results:A total of 2300 samples obtained from wild migratory birds of 8 orders were collected and tested. Influenza was detected in 185 birds of 3 orders. Species of family Anatidae(order Anseriformes) such as European Teal(Anas crecca), Garganey Teal(A. querquedula), and Shoveler(A. clypeata) play the main role in AIV circulation in the south of Western Siberia. The proportion of viral carriers among waterfowl ranged from 5.6 to 20% in 2007-2014. The order Charadriiformes had lower virus isolation rates of not more than 1.4%.Conclusions:Wild migratory waterfowl of orders Anseriformes and Charadriiformes are the main reservoir of AIV in the south of Western Siberia. This area plays a key role in persistence, evolution, and geographical distribution of avian influenza.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (CAS) (XDB29010102)National Natural Science Foundation of China (NSFC) (91957124,82161148010,32041010)+4 种基金Self-supporting Program of Guangzhou Laboratory (SRPG22-001)National Science and Technology Infrastructure of China (National Pathogen Resource Center-NPRC-32)Management Strategy of the Tertiary Prevention and Treatment of Diabetes Based on DIP system (supported by China Health Promotion Foundation)supported by the Youth Innovation Promotion Association of CAS (Y2021034)Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine (ZYYCXTD-D-202208)。
文摘Severe acute respiratory syndrome coronavirus 2(SARSCo V-2)infection can result in more severe syndromes and poorer outcomes in patients with diabetes and obesity.However,the precise mechanisms responsible for the combined impact of coronavirus disease 2019(COVID-19)and diabetes have not yet been elucidated,and effective treatment options for SARS-Co V-2-infected diabetic patients remain limited.To investigate the disease pathogenesis,K18-h ACE2 transgenic(h ACE2^(Tg))mice with a leptin receptor deficiency(h ACE2-Lepr^(-/-))and high-fat diet(h ACE2-HFD)background were generated.The two mouse models were intranasally infected with a 5×10^(5) median tissue culture infectious dose(TCID_(50))of SARSCo V-2,with serum and lung tissue samples collected at 3days post-infection.The h ACE2-Lepr^(-/-)mice were then administered a combination of low-molecular-weight heparin(LMWH)(1 mg/kg or 5 mg/kg)and insulin via subcutaneous injection prior to intranasal infection with1×10^(4) TCID_(50)of SARS-Co V-2.Daily drug administration continued until the euthanasia of the mice.Analyses of viral RNA loads,histopathological changes in lung tissue,and inflammation factors were conducted.Results demonstrated similar SARS-Co V-2 susceptibility in h ACE2^(Tg)mice under both lean(chow diet)and obese(HFD)conditions.However,compared to the h ACE2-Lepr^(+/+)mice,h ACE2-Lepr^(-/-)mice exhibited more severe lung injury,enhanced expression of inflammatory cytokines and hypoxia-inducible factor-1α(HIF-1α),and increased apoptosis.Moreover,combined LMWH and insulin treatment effectively reduced disease progression and severity,attenuated lung pathological changes,and mitigated inflammatory responses.In conclusion,preexisting diabetes can lead to more severe lung damage upon SARS-Co V-2 infection,and LMWH may be a valuable therapeutic approach for managing COVID-19patients with diabetes.
基金supported by the National Key R&D Program of China(2016YFE0205800)National Science and Technology Major Project(2016ZX10004222)+5 种基金Emergency Technology Research Issue on Prevention and Control for Human Infection with A(H7N9)Avian Influenza Virus(10600100000015001206)intramural special grants for influenza virus research from the Chinese Academy of Sciences(KJZD-EWL15)Tianjin Research Program of the Application Foundation and Advanced Technology(14JCYBJC24400)the research project RFBR 17-04-01919a leading principal investigator of the NSFC Innovative Research Group(81621091)supported by the Youth Innovation Promotion Association of Chinese Academy of Sciences(CAS)(2017122)
文摘Studies on influenza virus by Chinese Academy of Sciences(CAS)could be traced back as early as 2005 by the CAS Key Laboratory of Pathogenic Microbiology and Immunology(CASPMI),who discovered that Qinghai-like Clade 2.2H5N1 subtype highly pathogenic avian influenza virus(HPAIV)first caused severe outbreak in wild birds in Qinghai Lake(Liu et al.,2005).
文摘The ongoing pandemic of coronavirus disease 2019 (COVID-19), caused by infection with human coronavirus 2019 (HCoV-19/SARS-CoV-2/2019-nCoV), is a global threat to the human population. Here, we briefly summarize the available data for the zoonotic origins of HCoV-19, with reference to the other two epidemics of highly virulent coronaviruses, SARSCoV and MERS-CoV, which cause severe pneumonia in humans. We propose to intensify future efforts for tracing the origins of HCoV-19, which is a very important scientific question for the control and prevention of the pandemic.
基金supported by the National Key R&D Program of China(2023YFC2307500 and 2021YFC2701700)National Natural Science Foundation of China(82341115)+5 种基金Beijing Research Center for Respiratory Infectious Diseases(BJRID2024-003)Major Project of Guangzhou National Laboratory(GZNL2023A01001 and SRPG22-001)the National Science and Technology Infrastructure of China(National Pathogen Resource Center-NPRC-32)Y.B.is supported by the Youth Innovation Promotion Association of CAs(Y2021034)CAS Project for Young Scientists in Basic Research(YSBR-086)the Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine(ZYYCXTD-D-202208).
文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection often leads to pulmonary complications.Cardiovascular sequelae,including myocarditis and heart failure,have also been reported.Here,the study presents two fulminant myocarditis cases infected by SARS-CoV-2 exhibiting remarkable elevation of cardiac biomarkers without significant pulmonary injury,as determined by imaging examinations.Immunohistochemical staining reveals the viral antigen within cardiomyocytes,indicating that SARSCoV-2 could directly infect the myocardium.The full viral genomes from respiratory,anal,and myocardial specimens are obtained via next-generation sequencing.Phylogenetic analyses of the whole genome and spike gene indicate that viruses in the myocardium/pericardial effusion and anal swabs are closely related and cluster together yet diverge from those in the respiratory samples.In addition,unique mutations are found in the anal/myocardial strains compared to the respiratory strains,suggesting tissue-specific virus mutation and adaptation.These findings indicate genetically distinct SARS-CoV-2 variants have infiltrated and disseminated within myocardial tissues,independent of pulmonary injury,and point to different infection routes between the myocardium and respiratory tract,with myocardial infections potentially arising from intestinal infection.These findings highlight the potential for systemic SARS-CoV-2 infection and the importance of a thorough multi-organ assessment in patients for a comprehensive understanding of thepathogenesisof COVID-19.
基金supported by National Science and Technology Major Project of China (2015ZX09101044)Science & Technology Demonstration Project for Emerging Infectious Diseases Control and Prevention of Jiangsu Province, China (BE2015714 & BE2017749)Key Medical Discipline of Jiangsu Science & Technology Project of China (epidemiology,ZDXKA2016008)
文摘Human infections with influenza H7 subtypes, such as H7N9, have raised concerns worldwide. Here, we report a human infection with a novel influenza A(H7N4) virus. A 68 years-old woman with cardiovascular and cholecystic comorbidities developed rapidly progressed pneumonia with influenza-like-illness as initial symptom, recovered after 23 days-hospitalization including 8 days in ICU. Laboratory indicators for liver and blood coagulation dysfunction were observed. Oseltamivir phosphate, glucocorticoids and antibiotics were jointly implemented, with nasal catheterization of oxygen inhalation for this patient.We obtained the medical records and collected serial respiratory and blood specimens from her. We collected throat, cloacal and/or feces samples of poultry and wild birds from the patient's backyard, neighborhood, local live poultry markets(LPMs) and the nearest lake. All close contacts of the patient were followed up and sampled with throat swabs and sera. Influenza viruses and other respiratory pathogens were tested by real-time RT-PCR, viral culturing and/or sequencing for human respiratory and bird samples. Micro-neutralizing assay was performed for sera. A novel reassortant wild bird-origin H7N4 virus is identified from the patient and her backyard poultry(chickens and ducks) by sequencing, which is distinct from previously-reported avian H7N4 and H7N9 viruses. At least four folds increase of neutralizing antibodies to H7N4 was detected in her convalescent sera. No samples from close contacts, wild birds or other poultry were tested positive for H7N4 by real-time RT-PCR.
基金supported by the National Natural Science Foundation of China (81401312, 81373141, 81502857)National Grand Project on Prevention and Control of Major Infectious Diseases (2016ZX10004222-003)+3 种基金the intramural special grant for influenza virus research from the Chinese Academy of Sciences (KJZD-EW-L15)George F. Gao is a leading principal investigator of the National Natural Science Foundation of China Innovative Research Group (81621091)Weifeng Shi is supported by the Taishan Scholars program of Shandong Province (ts201511056)Yuhai Bi is supported by the Youth Innovation Promotion Association of Chinese Academy of Sciences (CAS) (2017122)
文摘Dear Editor,Avian influenza viruses (AIVs) have posed a serious threat to poultry production and public health. To date, more than fourteen AIV subtypes that are able to infect human beings have been documented. Also, it is suggested that new subtypes may be reported in the future, owing to the migration of wild birds and live poultry transportation (Gao, 2018).Poultry may act as a potential incubator for novel subtypes of avian influenza virus (Bi et al., 2016a; Bi et al., 2016b; Liu et al., 2014a; Su et al., 2017). Up to date, the H7N9 AIV emerged in February 2013 has caused 1,567 human cases,with a fatality rate of 39.2%(http://www.who.int/influenza/
基金supported by grants from the National Natural Science Foundation of China (31311120063,81470096,31570026,31471253)the Ministry of Education and Science of the Russian Federation (Chinese-Russian project:RFMEFI61315X0045)+3 种基金the intramural special grant for influenza virus research from the Chinese Academy of Sciences (KJZD-EW-L09)the IDRCAPEIR program (106915-001)Special Project of Ministry of Science and Technology (2013FY113500)supported by the “Taishan Scholar” project of Shandong Province
文摘A novel Clade 2.3.2.1c H5N1 reassortant virus caused several outbreaks in wild birds in some regions of China from late 2014 to 2015.Based on the genetic and phylogenetic analyses,the viruses possess a stable gene constellation with a Clade 2.3.2.1c HA,a H9N2-derived PB2 gene and the other six genes of Asian H5N1-origin.The Clade 2.3.2.1c H5N1 reassortants displayed a high genetic relationship to a human H5N1 strain(A/Alberta/01/2014).Further analysis showed that similar viruses have been circulating in wild birds in China,Russia,Dubai(Western Asia),Bulgaria and Romania(Europe),as well as domestic poultry in some regions of Africa.The affected areas include the Central Asian,East Asian-Australasian,West Asian-East African,and Black Sea/Mediterranean flyways.These results show that the novel Clade 2.3.2.1c reassortant viruses are circulating worldwide and may have gained a selective advantage in migratory birds,thus posing a serious threat to wild birds and potentially humans.
基金supported by RFBR(research project No.17-04-01919)the National Key Research and Development Project of China(2016YFE0205800)+3 种基金the National Science and Technology Major Project(2016ZX10004222)intramural special grants for influenza virus research from the Chinese Academy of Sciences(KJZD-EW-L15)supported by the Youth Innovation Promotion Association of Chinese Academy of Sciences(CAS)(2017122)supported by the Taishan Scholars program of Shandong Province(ts201511056)
文摘Dear Editor Marine mammals are widely distributed and can be found almost in all coastal waters and coastlines around the world.The interface areas between marine and terrestrial environments provide natural habitats for aquatic and semiaquatic mammals as well as for reservoir species of avian influenza viruses (AIV)(Runstadler et al.2013).
基金This work was supported by the National Natural Science Foundation of China(NSFC)(81788101,31870163,and 32100104)the CAMS Innovation Fund for Medical Sciences(2021-I2M-1-022)+6 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(CAS)(XDB29010102)CAS Southest Asia Biodiversity Research Institute(151C53KYSB20210023)Beijing Natural Science Foundation(L192007)National Pathogen Resource Center,and State Key Laboratory Special Fund(2060204)Y.B.is supported by the NSFC Outstanding Young Scholars(31822055)Youth Innovation Promotion Association of the CAS(2017122 and Y2021034)Overseas Expertise Introduction Center for Discipline Innovation(“111 Center”)(BP0820029).
文摘Innate immunity plays critical antiviral roles. The highly virulent avian influenza viruses (AIVs) H5N1, H7N9, and H5N6 can betterescape host innate immune responses than the less virulent seasonal H1N1 virus. Here, we report a mechanism by whichtranscriptional readthrough (TRT)-mediated suppression of innate immunity occurs post AIV infection. By using cell lines, mouselungs, and patient PBMCs, we showed that genes on the complementary strand (“trans” genes) influenced by TRT were involved inthe disruption of host antiviral responses during AIV infection. The trans-TRT enhanced viral lethality, and TRT abolishmentincreased cell viability and STAT1/2 expression. The viral NS1 protein directly bound to SSU72, and degradation of SSU72 inducedTRT. SSU72 overexpression reduced TRT and alleviated mouse lung injury. Our results suggest that AIVs infection induce TRT byreducing SSU72 expression, thereby impairing host immune responses, a molecular mechanism acting through the NS1-SSU72-trans-TRT-STAT1/2 axis. Thus, restoration of SSU72 expression might be a potential strategy for preventing AIV pandemics.
基金supported by the National Key R&D Program of China(2021YFC2300903,2021YFE0109100,and 2021YFC2301300)Strategic Priority Research Program of Chinese Academy of Sciences(CAS)(XDB29010102)+8 种基金National Natural Science Foundation of China(NSFC)(32161123001,82161148010,and 32041010)Beijing Natural Science Foundation(M22029 and L192007)CAS Southeast Asia Biodiversity Research Institute(151C53KYSB20210023)Shenzhen Science and Technology Research and Development Project(JCYJ20180504165549581)the National Science and Technology Infrastructure of China(National Pathogen Resource Center-NPRC-32)supported by the Special Program of China Postdoctoral Science Foundation(2020T130123ZX)supported by National Natural Science Foundation of China(NSFC)Outstanding Young Scholars(31822055)Youth Innovation Promotion Association of CAS(Y2021034)the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(ZYYCXTD-D-202208)。
文摘Since the 20th century,humans have lived through five pandemics caused by influenza A viruses(IAVs)(H1N1/1918,H2N2/1957,H3N2/1968,and H1N1/2009)and the coronavirus(CoV)severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).IAVs and CoVs both have broad host ranges and share multiple hosts.Virus co-circulation and even co-infections facilitate genetic reassortment among IAVs and recombination among CoVs,further altering virus evolution dynamics and generating novel variants with increased cross-species transmission risk.Moreover,SARS-CoV-2 may maintain longterm circulation in humans as seasonal IAVs.Co-existence and co-infection of both viruses in humans could alter disease transmission patterns and aggravate disease burden.Herein,we demonstrate how virus-host ecology correlates with the co-existence and co-infection of IAVs and/or CoVs,further affecting virus evolution and disease dynamics and burden,calling for active virus surveillance and countermeasures for future public health challenges.
文摘Dear Editor,Akabane disease is an arthropod-borne viral disease caused by the Akabane virus(AKAV)that can affect cattle,sheep,and goats.Inapparent infections in adults can lead months later to abortions,stillbirths,congenital defects,and death in newborns(Kurogi et al.,1976).Wild ruminants can also be affected,but abnormalities of the offspring in these species have not been reported.One report suggests that this virus can also cause clinical signs in pigs(Yanase et al.,2018).
基金supported by the National Key Research and Development Program of China (grant 2017YFC1200202)the Major Special Projects for Infectious Disease Research of China (grant 2016ZX10004222003)+1 种基金the National Natural Science Foundation of China (grants 81401312 and 81373141)supported by the Excellent Young Scientist Program of the NSFC (81822040)
文摘Influenza is one of the oldest infectious diseases affecting humans. Every influenza pandemic in history has ended with disastrous outcomes regarding public health and the social economy. This year marks the 100th anniversary of the Spanish flu (H1N1) outbreak of 1918, which is recognized as the most lethal natural event in recent history.
基金supported by the National Science and Technology Major Project(2016ZX10004222)the Sanming Project of Medicine in Shenzhen(ZDSYS201504301534057)+6 种基金the Key specialized fund for infectious diseases in Shenzhen City(No.201161)the intramural special grant for influenza virus research from the Chinese Academy of Sciences(KJZD-EW-L09 and KJZD-EWL15)the Shenzhen Science and Technology Research and Development Project(JCYJ20160427151920801 and JCYJ20160427153238750)G.F.G.is a leading principal investigator of the National Natural Science Foundation of China(NSFC)Innovative Research Group(81621091)supported by the Youth Innovation Promotion Association of Chinese Academy of Sciences(CAS)(2017122)G.W.is the recipient of a Banting Postdoctoral Fellowship from the Canadian Institutes of Health Research(CIHR)the President’s International Fellowship Initiative from the CAS
文摘The Zika virus(ZIKV) is an arbovirus that has spread rapidly worldwide within recent times. There is accumulating evidence that associates ZIKV infections with Guillain-Barré Syndrome(GBS) and microcephaly in humans. The ZIKV is genetically diverse and can be separated into Asian and African lineages. A rapid, sensitive, and specific assay is needed for the detection of ZIKV across various pandemic regions. So far, the available primers and probes do not cover the genetic diversity and geographic distribution of all ZIKV strains. To this end, we have developed a one-step quantitative reverse transcription polymerase chain reaction(qRT-PCR) assay based on conserved sequences in the ZIKV envelope(E) gene. The detection limit of the assay was determined to be five RNA transcript copies and 2.94 × 10^(–3) 50% tissue culture infectious doses(TCID50) of live ZIKV per reaction. The assay was highly specific and able to detect five different ZIKV strains covering the Asian and African lineages without nonspecific amplification, when tested against other flaviviruses. The assay was also successful in testing for ZIKV in clinical samples. Our assay represents an improvement over the current methods available for the detection ZIKV and would be valuable as a diagnostic tool in various pandemic regions.
基金This work was supported by the National Key Research and Development Program of China(2016YFD0500301,2020YFC0840900,2016YFE0205800)the Strategic Priority Research Program of the Chinese Academy of Sciences(CAS)(Grant No.XDA19090118 and XDB29010102)+2 种基金National Natural Science Foundation of China(NSFC)(Grant No.32041010).Y.B.is supported by the NSFC Outstanding Young Scholars(Grant No.31822055)Youth Innovation Promotion Association of CAS(Grant No.2017122).
文摘The ongoing pandemic of coronavirus disease 2019(COVID-19)caused by a novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2,also named as 2019-nCoV or HCoV-19)poses an unprecedented threat to public health(Zhu et al.,2020;Wang et al.,2020;Jiang et al.,2020).The novel HCoV-19 virus has rapidly spread into multiple countries across the world since it was first reported in December 2019.The World Health Organization(WHO)declared COVID-19 as a pandemic on 11th March 2020.As of 4th July,over 10 million confirmed COVID-19 cases have been reported in over 200 countries/regions with more than 0.5 million deaths,including 85,287 documented cases and 4,648 deaths in China(WHO,2020a).
基金supported by grants from the National Science and Technology Major Project of China (2016ZX10004222 and 2016YFC1200800)Strategic Priority Research Program of the Chinese Academy of Sciences (XDB29010102)+5 种基金Sanming Project of Medicine in Shenzhen (SZSM201412003)Shenzhen Municipal Government of China (JCYJ20160427151920801)Beijing Municipal Science & Technology Commission (Z161100000116049)the National Natural Science Foundation of China (NSFC) International Cooperation and Exchange Program (816110193)supported by the NSFC Outstanding Young Scholars (31822055)Youth Innovation Promotion Association of Chinese Academy of Sciences (CAS) (2017122)
文摘Dear Editor,In recent years,the incidence of human infections caused by emerging or re-emerging pathogens has rapidly increased.Diseases that were once regional now have the ability to spread globally in a short amount of time and pose a wider threat to public health(Weaver et al.2018).Yellow fever virus(YFV,family Flaviviridae,genus Flavivirus)is a mosquito-borne flavivirus that causes yellow fever in humans and has been endemic in Africa and Latin America for many years(Domingo et al.2018).
基金This study was supported by National Key Technologies Research and Development Program grants 2018YFC1200500 and 2018YFC1200600 to L.Y.and 2021YFC2300900 to Y.B.,Strategic Priority Research Program of Chinese Academy of Sciences XDB29010000 to W.L.and XDB29010102 to Y.B.,National Natural Science Foundation of China(NSFC)(32041010)NSFC Outstanding Young Scholars(31822055)Youth Innovation Promotion Association of CAS(2017122)to Y.B.
文摘Dear Editor,The ongoing SARS-CoV-2 pandemic has lasted for 2 years,causing a severe global impact on social development.With widespread vaccinations,the number of new infections has dropped significantly,but with the emergence of diverse novel variants of concern(VOCs)and variants of interest(VOIs),there has been a second or third epidemic wave in many countries.
基金This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(CAS)(Grant No.XDB29010102)National Natural Science Foundation of China(NSFC)(Grant No.31870163 and 32061123001)+2 种基金the Academic Promotion Programme of Shandong First Medical University(2019QL006)supported by the Taishan Scholars program of Shandong Province.Y.B.is supported by the NSFC Outstanding Young Scholars(Grant No.31822055)Youth Innovation Promotion Association of CAS(Grant No.2017122)。
文摘Dear Editor,Astroviruses(AstVs)are non-enveloped,single-stranded RNA viruses with a diameter of approximately 35 nm(Madeley and Cosgrove 1975).The genomes of AstVs range in size from 6.8 to 7.9 kb(De Benedictis et al.2011),consisting of a 5'-untranslated region(UTR),three open reading frames(ORFs),a 3'-UTR,and a poly-adenylated(polyA)tail(Pantin-Jackwood et al.2006).In 1975,AstVs were first discovered in faeces of infants(Madeley and Cosgrove 1975).Until now,a variety of animal species,including cows,sheep,pigs,dogs,deer,rats,bats,chickens,ducks,turkeys,sea lions and seals have been reported to be infected with AstVs(Tzipori et al.1981;Cattoli et al.2007;Chu et al.2008,2010;Atkins et al.2009;Toffan et al.2009;Rivera et al.2010;Guix et al.2013;Kang et al.2012;Reuter et al.2012a,2012b;Li et al.2021).Currently,AstVs comprise two genera,Mamastrovirus(MAstV)and Avastrovirus(AAstV).Herein,we describe three novel AAstVs identified from dead crow tissues.To our knowledge,this is the first report for identification of AstVs in crows.
基金This work was supported by the General Program of the National Natural Science Foundation of China(grant number 82073621&82172244)National Key Research and Development Program of China(grant number 2021YFC0863300)+1 种基金Beijing Municipal Science and Technology Project(Z211100002521018)Bill&Melinda Gates Foundation(Investment ID INV-006379).
文摘Emerging SARS-CoV-2 variants are the most serious problem for COVID-19 prophylaxis and treatment.To determine whether the SARS-CoV-2 vaccine strain should be updated following variant emergence like seasonal flu vaccine,the changed degree on antigenicity of SARS-CoV-2 variants and H3N2 flu vaccine strains was compared.The neutralization activities of Alpha,Beta and Gamma variants’spike protein-immunized sera were analysed against the eight current epidemic variants and 20 possible variants combining the top 10 prevalent RBD mutations based on the Delta variant,which were constructed using pseudotyped viruses.Meanwhile,the neutralization activities of convalescent sera and current inactivated and recombinant protein vaccine-elicited sera were also examined against all possible Delta variants.Eight HA protein-expressing DNAs elicited-animal sera were also tested against eight pseudotyped viruses of H3N2 flu vaccine strains from 2011–2019.Our results indicate that the antigenicity changes of possible Delta variants were mostly within four folds,whereas the antigenicity changes among different H3N2 vaccine strains were approximately 10–100-fold.Structural analysis of the antigenic characterization of the SARS-CoV-2 and H3N2 mutations supports the neutralization results.This study indicates that the antigenicity changes of the current SARS-CoV-2 may not be sufficient to require replacement of the current vaccine strain.
基金We thank all staff members in the Center of Biological Imaging(CBI),the Institute of Biophysics(IBP),and the Chinese Academy of Sciences(CAS)for assistance with data collection.This study was supported by the Strategic Priority Research Program of CAS(XDB29010000)the National Science and Technology Major Project(2018ZX10101004)+3 种基金the National Key Research and Development Program of China(2020YFC0845900)the National Natural Science Foundation of China(NSFC)(82041016,81871658,and 81802010)a grant from the Bill&Melinda Gates Foundation,and is partially supported by the Yanqi Lake Meeting organized by the Academic Divisions of CAS.M.W.is supported by the National Science and Technology Major Project(2018ZX09711003)the National Natural Science Foundation of China(NSFC)(81802007).R.P.is supported by the Young Elite Scientist Sponsorship Program(YESS)by the China Association for Science and Technology(CAST)(2018QNRC001).Y.S.is also supported by the Youth Innovation Promotion Association of CAS.
文摘The outbreak of severe acute respiratory syndrome coronavirus 2(SARSCoV-2)has developed into an unprecedented global pandemic.Nucleoside analogs,such as Remdesivir and Favipiravir,can serve as the firstline broad-spectrum antiviral drugs by targeting the viral polymerases.However,the underlying mechanisms for the antiviral efficacies of these drugs are far from well understood.Here,we reveal that Favipiravir,as a pyrazine derivative,could be incorporated into the viral RNA products by mimicking both adenine and guanine nucleotides.This drug thus inhibits viral replication mainly by inducing mutations in progeny RNAs,different from Remdesivir or other RNA-terminating nucleoside analogs that impair the elongation of RNA products.We further determined the cryo-EM structure of Favipiravir bound to the replicating polymerase complex of SARSCoV-2 in the pre-catalytic state.This structure provides a missing snapshot for visualizing the catalysis dynamics of coronavirus polymerase,and reveals an unexpected base-pairing pattern between Favipiravir and pyrimidine residues that may explain its capacity for mimicking both adenine and guanine nucleotides.These findings shed light on the mechanism of coronavirus polymerase catalysis and provide a rational basis for developing antiviral drugs to combat the SARS-CoV-2 pandemic.