Control of highly pathogenic avian influenza through vaccination

The stamping-out strategy has been used to control highly pathogenic avian influenza viruses in many countries,driven by the belief that vaccination would not be successful against such viruses and fears that avian influenza virus in vaccinated birds would evolve more rapidly and pose a greater risk to humans.In this review,we summarize the successes in controlling highly pathogenic avian influenza in China and make suggestions regarding the requirements for vaccine selection and effectiveness.In addition,we present evidence that vaccination of poultry not only eliminates human infection with avian influenza virus,but also significantly reduces and abolishes some harmful characteristics of avian influenza virus.

Emergence of highly pathogenic avian influenza A(H5N8)clade 2.3.4.4b viruses in grebes in Inner Mongolia and Ningxia,China,in 2021

Highly pathogenic avian influenza(HPAI)subtype H5Nx viruses have spread globally and are a major concern for poultry,wild birds,mammals,and even humans(de Vries et al.2015;Zeng et al.2022).The hemagglutinin(HA)genes of H5 subtype viruses have evolved into multiple clades and some of these clades have been further divided into subclades(Cui et al.2022).Clade 2.3.4.4H5N8 HPAI viruses(HPAIVs)have caused several waves of disease outbreaks in wild birds and domestic poultry(Wang et al.2022).

Antibodies elicited by Newcastle disease virus-vectored H7N9 avian influenza vaccine are functional in activating the complement system

H7N9 subtype avian influenza virus poses a great challenge for poultry industry.Newcastle disease virus(NDV)-vectored H7N9 avian influenza vaccines(NDV_(vec)H7N9)are effective in disease control because they are protective and allow mass administration.Of note,these vaccines elicit undetectable H7N9-specific hemagglutination-inhibition(HI)but high IgG antibodies in chickens.However,the molecular basis and protective mechanism underlying this particular antibody immunity remain unclear.Herein,immunization with an NDV_(vec)H7N9 induced low anti-H7N9 HI and virus neutralization titers but high levels of hemagglutinin(HA)-binding IgG antibodies in chickens.Three residues(S150,G151 and S152)in HA of H7N9 virus were identified as the dominant epitopes recognized by the NDV_(vec)H7N9 immune serum.Passively transferred NDV_(vec)H7N9 immune serum conferred complete protection against H7N9 virus infection in chickens.The NDV_(vec)H7N9 immune serum can mediate a potent lysis of HA-expressing and H7N9 virus-infected cells and significantly suppress H7N9 virus infectivity.These activities of the serum were significantly impaired after heat-inactivation or treatment with complement inhibitor,suggesting the engagement of the complement system.Moreover,mutations in the 150-SGS-152 sites in HA resulted in significant reductions in cell lysis and virus neutralization mediated by the NDV_(vec)H7N9 immune serum,indicating the requirement of antibody-antigen binding for complement activity.Therefore,antibodies induced by the NDV_(vec)H7N9 can activate antibody-dependent complement-mediated lysis of H7N9 virus-infected cells and complement-mediated neutralization of H7N9 virus.Our findings unveiled a novel role of the complement in protection conferred by the NDV_(vec)H7N9,highlighting a potential benefit of engaging the complement system in H7N9 vaccine design.

High-Value-Added Utilization of Turpentine:Screening of Anti-Influenza Virus Agents fromβ-Pinene Derivatives

Turpentine is a renewable and resourceful forest product.The deep processing and utilization of turpentine,particularly its primary componentβ-pinene,has garnered widespread attention.This study aimed to synthesize 40 derivatives ofβ-pinene,including nopinone,3-cyanopyridines of nopinone,myrtanyl acid,myrtanyl acylthioureas,and myrtanyl amides.We assessed the antiviral activities of theseβ-pinene derivatives against influenza virus A/Puerto Rico/8/34(H1N1)using the 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method.Theβ-pinene derivatives were used before and after cellular infection with the influenza virus to evaluate their preventive and therapeutic effects against the H1N1 virus.The results showed that only compound 10o exhibited a preventive effect against the H1N1 virus with a half-maximal inhibitory concentration(IC50)value of 47.6μmol/L.Among the compounds,4e,4i,and 4l demonstrated therapeutic effects against cellular infection,with compound 4e displaying the most potent therapeutic effect(IC50=17.5μmol/L),comparable to the positive control ribavirin.These findings indicated that certainβ-pinene derivatives exhibited in vitro antiviral activity against the H1N1 influenza A virus,warranting further investigation as potential anti-influenza agents.

Establishment of a humanized ST6GAL1 mouse model for influenza research

Background:This study aimed to construct and characterize a humanized influenza mouse model expressing hST6GAL1.Methods:Humanized fragments,consisting of the endothelial cell-specific K18 promoter,human ST6GAL1-encoding gene,and luciferase gene,were microinjected into the fertilized eggs of mice.The manipulated embryos were transferred into the oviducts of pseudopregnant female mice.The offspring were identified using PCR.Mice exhibiting elevated expression of the hST6GAL1 gene were selectively bred for propagation,and in vivo analysis was performed for screening.Expression of the humanized gene was tested by performing immunohistochemical(IHC)analysis.Hematologic and biochemical analyses using the whole blood and serum of humanized hST6GAL1 mice were performed.Results:Successful integration of the human ST6GAL1 gene into the mouse genome led to the overexpression of human SiaT ST6GAL1.Seven mice were identified as carrying copies of the humanized gene,and the in vivo analysis indicated that hST6GAL1gene expression in positive mice mirrored influenza virus infection characteristics.The IHC results revealed that hST6GAL1 was expressed in the lungs of humanized mice.Moreover,the hematologic and biochemical parameters of the positive mice were within the normal range.Conclusion:A humanized influenza mouse model expressing the hST6GAL1 gene was successfully established and characterized.

Pudilan Xiaoyan oral liquid regulates tissue inflammation and apoptosis in mice with influenza virus pneumonia

Background:The influenza A virus is the primary cause of respiratory infections and poses a global health risk.Pudilan Xiaoyan oral liquid(PDL)exhibits anti-inflammatory and immunomodulatory properties.PDL is commonly employed in clinical practice to manage upper respiratory tract infections.However,there is still much to uncover regarding its potential therapeutic mechanism.Methods:Institute of cancer research mice were infected with influenza A virus via nasal drip.The general state of the mice,lung index,and lung index inhibition rate were used to evaluate the efficacy of PDL.Enzyme-linked immunosorbent assay,western blotting,and immunohistochemistry were used to observe the presence of proteins and cytokines in the lung tissue.Apoptosis was evaluated using the TUNEL assay.Results:PDL improved the mental state of influenza A virus-infected mice,reduced the lung index,and inhibited viral replication.The expression of interleukin-1βand tumor necrosis factor-αwere decreased,whereas the expression of interleukin-10 in the lung tissue was increased due to PDL treatment.In addition,PDL treatment modulated Toll-like receptor 4 and MyD88 expressions in the lung tissues.PDL significantly reduced apoptosis and decreased cleaved caspase-3 and PARP levels,whereas increased B-cell lymphoma-2 expression in the lung tissue.Notably,the moderate-dose group of PDL exhibited a more pronounced effect.These findings indicate that PDL exerts a protective effect against pneumonia injury in influenza A virus-infected mice.Conclusion:PDL inhibited the inflammatory response and regulated apoptosis by regulating Toll-like receptor 4 and MyD88 protein expressions,thereby protecting the lung tissue from viral infection-induced lung tissue injury.

A Comparative Study of Myocardial Damage Caused by Novel Coronavirus Infection and Influenza A Virus Infection in Children during the COVID-19 Epidemic Period

Objective: To explore the comparative study of myocardial damage in children infected with COVID-19 and influenza A virus during the COVID-19 pandemic. Method: Retrospective analysis of myocardial injury caused by COVID-19 infection and influenza A virus infection in children during the COVID-19 from October 2022 to May 2023, including 106 cases of COVID-19 infection, that is, the COVID-19 group;And 164 cases of influenza A virus infection, namely, H1N1 group;Two groups were tested for various indicators of myocardial enzyme spectrum, and the situation of myocardial injury was compared between the two groups. Result: In the enrolled cases, there was no statistically significant difference in the prevalence rate of men and women in the COVID-19 group (P > 0.05);There was no statistically significant difference in the average age between men and women (P > 0.05);The comparison of the incidence rates between males and females in the H1N1 group showed a statistically significant difference (P 0.05);There was no statistically significant difference in the average age between the two groups of girls (P > 0.05). A comparison between two groups of various indicators of myocardial enzyme spectra showed that the results of AST, -HBDH and LDH were statistically significant (P 0.05). Conclusion: Both COVID-19 infection and influenza A virus infection in children have different degrees of myocardial damage, but COVID-19 infection causes more myocardial damage than influenza A virus infection, and influenza A virus is more prone to myocardial infarction, which deserves our attention.

A Rare Case of Aortic Valve Endocarditis and Acute Meningitis Due to Haemophilus influenzae

HACEK organisms represent a rare but important group of causative pathogens in endocarditis. These bacteria have historically been associated with culture-negative endocarditis;however, modern laboratory techniques have made this less common. In this case, we present a 74-year-old man who presented with acute onset altered mentation, fever, and sepsis. He was ultimately found to have Haemophilus influenzae meningitis, cerebral empyema, aortic valve endocarditis, psoas myositis, and L2 - L3 diskitis with osteomyelitis. Although HACEK organisms are commonly found in the oropharynx and upper respiratory tract in humans, our patient did not report recent preceding dental or ENT procedures. H. influenzae is responsible for approximately 0.16% of all cases of bacterial endocarditis, representing a very limited subset. Although generally considered low virulent pathogens, this case demonstrates the unusual extent of infection from a HACEK organism, H. influenzae, causing aortic valve endocarditis as well as atypical non-cardiac sequelae, including acute meningitis.

Forecast the Influenza Pandemic Using Machine Learning

Forecasting future outbreaks can help in minimizing their spread.Influenza is a disease primarily found in animals but transferred to humans through pigs.In 1918,influenza became a pandemic and spread rapidly all over the world becoming the cause behind killing one-third of the human population and killing one-fourth of the pig population.Afterwards,that influenza became a pandemic several times on a local and global levels.In 2009,influenza‘A’subtype H1N1 again took many human lives.The disease spread like in a pandemic quickly.This paper proposes a forecasting modeling system for the influenza pandemic using a feed-forward propagation neural network(MSDII-FFNN).This model helps us predict the outbreak,and determines which type of influenza becomes a pandemic,as well as which geographical area is infected.Data collection for the model is done by using IoT devices.This model is divided into 2 phases:The training phase and the validation phase,both being connected through the cloud.In the training phase,the model is trained using FFNN and is updated on the cloud.In the validation phase,whenever the input is submitted through the IoT devices,the system model is updated through the cloud and predicts the pandemic alert.In our dataset,the data is divided into an 85%training ratio and a 15%validation ratio.By applying the proposed model to our dataset,the predicted output precision is 90%.

Phylogenetic and epidemiological characteristics of H9N2 avian influenza viruses in Shandong Province, China from 2019 to 2021

H9N2 avian influenza virus(AIV) has widely circulated in poultry worldwide and sporadic infections in humans and mammals. During our surveillance of chicken from 2019 to 2021 in Shandong Province, China, we isolated 11 H9N2AIVs. Phylogenetic analyses showed that the eight gene segments of the 11 isolates were closely related to several sublineages of Eurasian lineage: BJ/94-like clades(HA and NA genes), G1-like clades(PB2 and M genes), and SH/F/98-like clades(PB1, PA, NP and NS genes). The isolates showed mutation sites that preferentially bind to humanlike receptors(HA) and mammalian fitness sites(PB2, PB1 and PA), as well as mutations in antigen and drug resistance sites. Moreover, studies with mice revealed four isolates with varying levels of pathogenicity. The average antibody titer of the H9N2 AIVs was 8.60 log2. Based on our results, the epidemiological surveillance of H9N2 AIVs should be strengthened.

H7N9 avian influenza with first manifestation of occipital neuralgia:A case report

BACKGROUND Most of the first symptoms of avian influenza are respiratory symptoms,and cases with occipital neuralgia as the first manifestation are rarely reported.CASE SUMMARY A middle-aged patient complaining of paroxysmal pain behind the ear was admitted to our hospital.The patient’s condition changed rapidly,and high fever,unexpected respiratory failure,and multiple organ failure developed rapidly.The patient was diagnosed with H7N9 avian influenza based on etiology.CONCLUSION We believe that the etiology of occipital neuralgia is complex and could be the earliest manifestation of severe diseases.The possibility of an infectious disease should be considered when occipital neuralgia is accompanied by fever.Avian influenza is one of these causative agents.

Altered gene expression in human brain microvascular endothelial cells in response to the infection of influenza H1N1 virus

Influenza viruses not only cause respiratory illness,but also have been reported to elicit neurological manifestations following acute viral infection.The central nervous system(CNS)has a specific defense mechanism against pathogens structured by cerebral microvasculature lined with brain endothelial cells to form the blood–brain barrier(BBB).To investigate the response of human brain microvascular endothelial cells(hBMECs)to the Influenza A virus(IAV),we inoculated the cells with the A/WSN/33(H1N1)virus.We then conducted an RNAseq experiment to determine the changes in gene expression levels and the activated disease pathways following infection.The analysis revealed an effective activation of the innate immune defense by inducing the pattern recognition receptors(PRRs).Along with the production of proinflammatory cytokines,we detected an upregulation of interferons and interferon-stimulated genes,such as IFN-β/λ,ISG15,CXCL11,CXCL3 and IL-6,etc.Moreover,infected hBMECs exhibited a disruption in the cytoskeletal structure both on the transcriptomic and cytological levels.The RNAseq analysis showed different pathways and candidate genes associated with the neuroactive ligand-receptor interaction,neuroinflammation,and neurodegenerative diseases,together with a predicted activation of the neuroglia.Likewise,some genes linked with the mitochondrial structure and function displayed a significantly altered expression.En masse,this data supports that hBMECs could be infected by the IAV,which induces the innate and inflammatory immune response.The results suggest that the influenza virus infection could potentially induce a subsequent aggravation of neurological disorders.

Inflammatory pseudotumors in the liver associated with influenza:A case report

BACKGROUND Inflammatory pseudotumor(IPT)is a rare and benign lesion that mimics malignancy and can develop in any part of the body.The pathophysiology and etiology of these quasineoplastic lesions remain unclear.CASE SUMMARY We report a case of a 65-year-old male who presented with fevers,night sweats,and unintentional weight loss following an influenza infection and was found to have multiple hepatic IPT’s following an extensive work up.CONCLUSION Our case highlights the importance of considering hepatic IPT’s in the differential in a patient who presents with symptoms and imaging findings mimicking malignancy shortly following a viral infection.

Involvement of Dectin-2 in the Innate Inflammatory Response Triggered by Influenza Virus Hemagglutinin

C-type lectin receptors (CLRs) are representative pattern recognition receptors that recognize microbial polysaccharides expressed on antigen-presenting cells. In the present study, we carried out further detailed analysis on the involvement of Dectin-2, a CLR that senses high mannose polysaccharide, in innate immune responses induced by influenza virus hemagglutinin (HA). Treatment of HA with periodate or PNGase F induced lower interleukin (IL)-12p40 secretion by conventional dendritic cells (DCs) compared with the untreated group. In contrast, treatment with O-glycosidase did not affect cytokine production. Green fluorescent protein expression in canonical Dectin-2-transducing cells was approximately 3% - 12% following HA stimulation, except with the A/H1N1pdm09 subtype HA. This expression was markedly reduced in cells possessing mutated amino acids in the carbohydrate recognition domain of Dectin-2, especially following stimulation with HA derived from the A/H3N2 subtype. Interferon (IFN)-α production from CD11c+Siglec-H+PDCA-1+ plasmacytoid DCs was significantly increased in Dectin-2 knockout mice compared with wild-type mice upon stimulation with HA except for the B/Yamagata lineage HA. These results suggested that Dectin-2 is involved in initiating inflammatory responses via mannose polysaccharide on HA. However, other mechanisms may function in the antiviral response, including the type I IFN axis.

Inhibition of cellular RNA methyltransferase abrogates influenza virus capping and replication

Orthomyxo- and bunyaviruses steal the 5' cap portion of host RNAs to prime their own transcription in a process called "capsnatching." We report that RNA modification of the cap portion by host 2'-O-ribose methyltransferase 1 (MTr1) is essential for theinitiation of influenza A and B virus replication, but not for other cap-snatching viruses. We identified with in silico compoundscreening and functional analysis a derivative of a natural product from Streptomyces, called trifluoromethyl-tubercidin (TFMT),that inhibits MTr1 through interaction at its S-adenosyl-l-methionine binding pocket to restrict influenza virus replication.Mechanistically, TFMT impairs the association of host cap RNAs with the viral polymerase basic protein 2 subunit in human lungexplants and in vivo in mice. TFMT acts synergistically with approved anti-influenza drugs.

Rapid Detection of Haemophilus influenzae and Haemophilus parainfluenzae in Nasopharyngeal Swabs by Multiplex PCR

Objective To establish multiplex PCR-based assays for detecting H.influenzae and H.parainfluenzae. And the PCR-based assays were applied to detect the carriage rates of H.influenzae and H.parainfluenzae in nasopharyngeal swab specimens which were collected from healthy children. Methods Multiplex primers for species-specific PCR were designed by using DNAstar soft based on the sequences of 165 rRNA genes from genus Haemophilus to detect H.influenzae and H.parainfluenzae. Results The sensitivity of the 165 rRNA PCR assay for detecting H.influenzae and H.parainfluenzae was 97.53% and 100% respectively, and the specificity was 95.89% and 96.63% respectively. Youden＇s Index on the ability to detect H.influenzae and H.parainfluenzae was 0.9342 and 0.9663 respectively. 666 nasopharyngeal swab specimens were collected from healthy children. The detection rates of H.influenzae and H.parainfluenzae were 14.11% and 16.07% respectively by using isolation and culture methods. The detection rates of H.influenzae and H.parainfluenzae were 43.54% and 57.96% respectively by 165 rRNA PCR assays. The carriage rates of serotypes a, b, c, d, e, f and non-typeable isolates were 0% （0/666）, 0.15% （1/666）, 1.20% （8/666）, 0.15% （1/666）, 1.20% （8/666）, 1.80% （12/666）, 95.50% （636/666） respectively. Conclusion The multiplex PCR assays were very rapid, reliable and feasible methods for detection of H.influenzae and H.parainfluenzae in pharyngeal swab specimens which were compared to conventional isolation and culture methods. 95.5% of H.influenzae strains in healthy children were nontypeable. The encapsulated or typable strains were mainly three serotypes which was c, e, and f serotype.

Epidemiology of influenza viruses from 2009-2013-A sentinel surveillance report from Union territory of Puducherry, India

Objective: To report the i ndings of inl uenza surveillance programme from Union territory of Puducherry and to document the clinical and epidemiological data of inl uenza viruses over a i ve year period from 2009-2013. Methods: Respiratory samples were collected from patients with influenza-like illness from 2009-2013 as part of routine diagnostic and surveillance activity. Detection of pandemic inl uenza A(H1N1) 2009, inl uenza A(H3N2) and inl uenza B was done using Real-time PCR. Results: Of the total 2 247 samples collected from patients with inl uenza-like illness during the study period 287(12.7%) and 92(4.0%) were positive for inl uenza A(H1N1) 2009 and inl uenza A(H3N2) respectively. A subset of 557 of these samples were also tested for inl uenza B and 24(4.3%) were positive. Signii cantly higher positivity rate for both viruses was observed in adults when compared with children. The peak positivity of influenza A(H1N1) 2009 was observed in 2009 followed by 2012, while that of inl uenza A(H3N2) was more uniformly distributed with the exception of 2012. Overall mortality rate due to influenza A(H1N1) 2009 was 7.6% while it was 1% for influenza A(H3N2). Each year influenza-like illness and influenza virus activity coincided with period of high rainfall and low temperature except in the first half of 2012. Conclusions: As the sole referral laboratory in this region, the data provides a comprehensive picture of inl uenza activity. This information will be useful in future planning of the vaccine schedule and inl uenza pandemic preparedness.

In silico modification of oseltamivir as neuraminidase inhibitor of influenza A virus subtype H1N1

This research focused on the modification of the functional groups of oseltamivir as neuraminidase inhibitor against influenza A virus subtype H1N1.Interactions of three of the best ligands were evaluated in the hydrated state using molecular dynamics simulation at two different temperatures.The docking result showed that AD3BF2 D ligand（N-[（1S,6R）-5-amino-5-{[（2R,3S,4S）-3,4-dihydroxy-4-（hydroxymethyl） tetrahydrofuran-2-yl]oxy}-4-formylcyclohex-3-en-1-yl]acetamide-3-（1-ethylpropoxy）-1-cyclohexene-1-carboxylate） had better binding energy values than standard oseltamivir.AD3BF2 D had several interactions,including hydrogen bonds,with the residues in the catalytic site of neuraminidase as identified by molecular dynamics simulation.The results showed that AD3BF2 D ligand can be used as a good candidate for neuraminidase inhibitor to cope with influenza A virus subtype H1N1.

Superior mesenteric vein thrombosis induced by influenza infection:A case report

BACKGROUND Among the various types and causes of mesenteric ischemia,superior mesenteric vein(SMV)thrombosis is a rare and ambiguous disease.If a patient presents with SMV thrombosis,past medical history should be reviewed,and the patient should be screened for underlying disease.SMV thrombosis may also occur due to systemic infection.In this report,we describe a case of SMV thrombosis complicated by influenza B infection.CASE SUMMARY A 64-year-old male visited the hospital with general weakness,muscle aches,fever,and abdominal pain.The patient underwent computed tomography(CT)and was diagnosed with SMV thrombosis.Since the patient’s muscle pain and fever could not be explained by the SMV thrombosis,the clinician performed a test for influenza,which produced a positive result for influenza B.The patient had a thrombus in the SMV only,with no invasion of the portal or splenic veins,and was clinically stable.Anticoagulation treatment was prescribed without surgery or other procedures.The follow-up CT scan showed improvement,and the patient was subsequently discharged with continued oral anticoagulant treatment.CONCLUSION This case provides evidence that influenza may be a possible risk factor for SMV thrombosis.If unexplained abdominal pain is accompanied by an influenza infection,examination of an abdominal CT scan may be necessary to screen for possible SMV thrombosis.

不变与变:从“SARS”到“Swine Influenza”的中文译名谈起

SARS与Swine Influenza为发生在本世纪初的两场重大传染疾病,其中SARS的中文译名一直未变,译为"非典";Swine Influenza则从开始的"猪流感"更名为"甲型H1N1流感"。本文尝试从翻译与传播的视角探讨这两种疾病中文译名的不变与变,分析背后的原因,并提出SARS中文译名的改进译法。