Identification of novel mammalian viruses in tree shrews(Tupaia belangeri chinensis)

The Chinese tree shrew(Tupaia belangeri chinensis),a member of the mammalian order Scandentia,exhibits considerable similarities with primates,including humans,in aspects of its nervous,immune,and metabolic systems.These similarities have established the tree shrew as a promising experimental model for biomedical research on cancer,infectious diseases,metabolic disorders,and mental health conditions.Herein,we used metatranscriptomic sequencing to analyze plasma,as well as oral and anal swab samples,from 105 healthy asymptomatic tree shrews to identify the presence of potential zoonotic viruses.In total,eight mammalian viruses with complete genomes were identified,belonging to six viral families,including Flaviviridae,Hepeviridae,Parvovirinae,Picornaviridae,Sedoreoviridae,and Spinareoviridae.Notably,the presence of rotavirus was recorded in tree shrews for the first time.Three viruses-hepacivirus 1,parvovirus,and picornavirus-exhibited low genetic similarity(<70%)with previously reported viruses at the whole-genome scale,indicating novelty.Conversely,three other viruses-hepacivirus 2,hepatovirus A and hepevirus-exhibited high similarity(>94%)to known viral strains.Phylogenetic analyses also revealed that the rotavirus and mammalian orthoreovirus identified in this study may be novel reassortants.These findings provide insights into the diverse viral spectrum present in captive Chinese tree shrews,highlighting the necessity for further research into their potential for crossspecies transmission.

Substitutions of stem-loop subdomains in internal ribosome entry site of Senecavirus A:Impacts on rescue of sequence-modifying viruses

Senecavirus A(SVA)has a positive-sense,single-stranded RNA genome.Its 5´untranslated region harbors an internal ribosome entry site(IRES),comprising 10 larger or smaller stem-loop structures(including a pseudoknot)that have been demonstrated to be well conserved.However,it is still unclear whether each stem-loop subdomain,such as a single stem or loop,is also highly conserved.To clarify this issue in the present study,a set of 29 SVA cDNA clones were constructed by site-directed mutagenesis(SDM)on the IRES.The SDM-modified scenarios included:(1)stem-formed complementary sequences exchanging with each other;(2)loop transversion;(3)loop transition;and(4)point mutations.All cDNA clones were separately transfected into cells for rescuing viable viruses,whereas only four SVAs of interest could be recovered,and were genetically stable during 20 passages.One progeny grew significantly slower than the other three did.The dual-luciferase reporter assay showed that none of the SDM-modified IRESes significantly inhibited the IRES activity.Our previous study indicated that a single motif from any of the ten stem structures,if completely mutated,would cause the failure of virus recovery.Interestingly,our present study revealed three stem structures,whose individual complementary sequences could exchange with each other to rescue sequence-modifying SVAs.Moreover,one apical loop was demonstrated to have the ability to tolerate its own full-length transition,also having no impact on the recovery of sequence-modifying SVA.The present study suggested that not every stem-loop structure was strictly conserved in its conformation,while the full-length IRES itself was well conserved.This provides a new research direction on interaction between the IRES and many factors.

Efficacy and mechanisms of Traditional Chinese Medicine prevention and treatment for respiratory viruses

Respiratory virus infection was the most common viral infection in clinical practice with the greatest impact,including the Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),posing a huge threat to the world's public health and human life safety.Commonly used antiviral drugs have obvious side effects and a narrow scope of application.Respiratory viruses are susceptible to infection,mutation,and prevalence,which also pose challenges to traditional antiviral drugs and vaccine development.Traditional Chinese Medicine(TCM)has a long history of treating infectious diseases,with many herbs and compounds.Its multi-component,multi-target and multi-path characteristics have made it have great advantages and potential in the development of new anti-respiratory virus drugs.This review summarized TCM for the prevention and treatment of common respiratory viruses,and provided new strategies for the research and development of new TCM antiviral drugs and for responding to infectious respiratory virus diseases.

Bat pluripotent stem cells reveal unusual entanglement between host and viruses

Bats are distinctive among mammals due to their ability to fly, use laryngeal echolocation, and tolerate viruses. However,there are currently no reliable cellular models for studying bat biology or their response to viral infections. Here, we createdinduced pluripotent stem cells (iPSCs) from two species of bats: the wild greater horseshoe bat (Rhinolophus ferrumequinum) andthe greater mouse-eared bat (Myotis myotis). The iPSCs from both bat species showed similar characteristics and had a geneexpression profile resembling that of cells attacked by viruses. They also had a high number of endogenous viral sequences,particularly retroviruses. These results suggest that bats have evolved mechanisms to tolerate a large load of viral sequences andmay have a more intertwined relationship with viruses than previously thought. Further study of bat iPSCs and their differentiatedprogeny will provide insights into bat biology, virus host relationships, and the molecular basis of bats' special traits.

Bat pluripotent stem cells reveal unusual entanglement between host and viruses

Bats are distinctive among mammals due to their ability to fly,use laryngeal echolocation,and tolerate viruses.However,there are currently no reliable cellular models for studying bat biology or their response to viral infections.Here,we created induced pluripotent stem cells(iPSCs)from two species of bats:the wild greater horseshoe bat(Rhinolophus ferrumequinum)and the greater mouse-eared bat(Myotis myotis).The iPSCs from both bat species showed similar characteristics and had a gene expression profile resembling that of cells attacked by viruses.They also had a high number of endogenous viral sequences,particularly retroviruses.These results suggest that bats have evolved mechanisms to tolerate a large load of viral sequences and may have a more intertwined relationship with viruses than previously thought.Further study of bat iPSCs and their differentiated progeny will provide insights into bat biology,virus host relationships,and the molecular basis of bats'special traits.

Surveillance of arthropod-borne viruses in Benin,West Africa 2020–2021:detection of dengue virus 3 in Aedes aegypti(Diptera:Culicidae)

Dear Editor,Dengue virus(DENV,family Flaviviridae,genus Flavivirus)serotypes 1 to 4(DENV-1,-2,-3,and-4)are responsible for more than 100 million infections per year worldwide.Symptoms of DENV infection can be diverse,reaching from an acute febrile illness to the more severe,sometimes fatal dengue haemorrhagic fever/dengue shock syndrome.

Progress in oncolytic viruses modified with nanomaterials for intravenous application

In oncolytic virus(OV)therapy,a critical component of tumor immunotherapy,viruses selectively infect,replicate within,and eventually destroy tumor cells.Simultaneously,this therapy activates immune responses and mobilizes immune cells,thereby eliminating residual or distant cancer cells.However,because of OVs’high immunogenicity and immune clearance during circulation,their clinical applications are currently limited to intratumoral injections,and their use is severely restricted.In recent years,numerous studies have used nanomaterials to modify OVs to decrease virulence and increase safety for intravenous injection.The most commonly used nanomaterials for modifying OVs are liposomes,polymers,and albumin,because of their biosafety,practicability,and effectiveness.The aim of this review is to summarize progress in the use of these nanomaterials in preclinical experiments to modify OVs and to discuss the challenges encountered from basic research to clinical application.

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.

Rapid inactivation of human respiratory RNA viruses by deep ultraviolet irradiation from light-emitting diodes on a high-temperatureannealed AlN/Sapphire template

Efficient and eco-friendly disinfection of air-borne human respiratory RNA viruses is pursued in both public environment and portable usage.The AlGaN-based deep ultraviolet(DUV)light-emission diode(LED)has high practical potentials because of its advantages of variable wavelength,rapid sterilization,environmental protection,and miniaturization.Therefore,whether the emission wavelength has effects on the disinfection as well as whether the device is feasible to sterilize various respiratory RNA viruses under portable conditions is crucial.Here,we fabricate AlGaN-based DUV LEDs with different wavelength on high-temperature-annealed(HTA)AlN/Sapphire templates and investigate the inactivation effects for several respiratory RNA viruses.The AlN/AlGaN superlattices are employed between the template and upper n-AlGaN to release the strong compressive stress(SCS),improving the crystal quality and interface roughness.DUV LEDs with the wavelength of 256,265,and 278 nm,corresponding to the light output power of 6.8,9.6,and 12.5 mW,are realized,among which the 256 nm-LED shows the most potent inactivation effect in human respiratory RNA viruses,including SARS-CoV-2,influenza A virus(IAV),and human parainfluenza virus(HPIV),at a similar light power density(LPD)of~0.8 mW/cm2 for 10 s.These results will contribute to the advanced DUV LED application of disinfecting viruses with high potency and broad spectrum in a portable and eco-friendly use.

Genetic Diversity Analysis of Badnaviruses Infecting Banana in Burkina Faso

Badnaviruses are serious plant pararetroviruses affecting banana and causes serious economic losses to banana production worldwide. This study aims to examine the variability of BSV and SCBV nature infecting banana in Burkina Faso. Polymerase Chain Reaction (PCR) used the Badna FP/RP specific primers for the RT/RNase H regions present in badnaviruses. The PCR yielded about 579 bp amplicons from banana infected by BSV and SCBV. The 38 BSV isolates recorded low nucleotide identity ranging from 58.9% - 98.1%. Based on percentage nucleotide sequence identity and phylogenetic analyse, BSV isolates were categorized into four groups: 1, 2, 3 and 4. Group 4 shared 76.9% - 100% identity with BSOL species. However, Groups 1 and 3 recorded a low identity ranging, from 76.8% - 79.2%, 68.8% - 79.7% with BSCV, and 72.8% - 79.0% between Group 2 and BSOLV. Groups 1, 2 and 3 were assigned to a potentially new BSV species. The two SCBV isolates recorded a low nucleotide identity of 68% among themselves indicating high diversity. In addition, SCBV_Cd and SCBV_CE showed high nucleotide identity 91.3% and 58.7% with SCBV_C and SCBV, when they were compared to all published SCBV genotypes. In addition, phylogenetic analysis revealed the segregation of SCBV isolates into two genotypes, SCBV_Cd in C and SCBV_CE segregated in a new genotype namely Z. Recombination analyses showed weak signatures of recombination among some of the BSV and SCBV sequences.

Viruses and autism: A Bi-mutual cause and effect

Autism spectrum disorder(ASD)is a group of heterogeneous,multi-factorial,neurodevelopmental disorders resulting from genetic and environmental factors interplay.Infection is a significant trigger of autism,especially during the critical developmental period.There is a strong interplay between the viral infection as a trigger and a result of ASD.We aim to highlight the mutual relationship between autism and viruses.We performed a thorough literature review and included 158 research in this review.Most of the literature agreed on the possible effects of the viral infection during the critical period of development on the risk of developing autism,especially for specific viral infections such as Rubella,Cytomegalovirus,Herpes Simplex virus,Varicella Zoster Virus,Influenza virus,Zika virus,and severe acute respiratory syndrome coronavirus 2.Viral infection directly infects the brain,triggers immune activation,induces epigenetic changes,and raises the risks of having a child with autism.At the same time,there is some evidence of increased risk of infection,including viral infections in children with autism,due to lots of factors.There is an increased risk of developing autism with a specific viral infection during the early developmental period and an increased risk of viral infections in children with autism.In addition,children with autism are at increased risk of infection,including viruses.Every effort should be made to prevent maternal and early-life infections and reduce the risk of autism.Immune modulation of children with autism should be considered to reduce the risk of infection.

Could autophagy dysregulation link neurotropic viruses to Alzheimer’s disease?

Neurotropic herpesviruses have been associated with the onset and progression of Alzheimer’s disease,a common form of dementia that afflicts a large percentage of elderly individuals.Interestingly,among the neurotropic herpesviruses,herpes simplex virus-1,human herpesvirus-6A,and human herpesvirus-6B have been reported to infect several cell types present in the central nervous system and to dysregulate autophagy,a process required for homeostasis of cells,especially neurons.Indeed autophagosome accumulation,indicating an unbalance between autophagosome formation and autophagosome degradation,has been observed in neurons of Alzheimer’s disease patients and may play a role in the intracellular and extracellular accumulation of amyloidβand in the altered protein tau metabolism.Moreover,herpesvirus infection of central nervous system cells such as glia and microglia can increase the production of oxidant species through the alteration of mitochondrial dynamics and promote inflammation,another hallmark of Alzheimer’s disease.This evidence suggests that it is worth further investigating the role of neurotropic herpesviruses,particularly human herpesvirus-6A/B,in the etiopathogenesis of Alzheimer’s disease.

Human hepatitis viruses-associated cutaneous and systemic vasculitis

Human hepatitis viruses(HHVs)include hepatitis A virus,hepatitis B virus(HBV),hepatitis C virus(HCV),hepatitis delta virus,and hepatitis E virus and can cause liver inflammation in their common human host.Usually,HHV is rapidly cleared by the immune system,following acute HHV invasion.The morbidities associated with hepatitis A virus and hepatitis E virus infection occur shortly after their intrusion,in the acute stage.Nevertheless,the viral infectious process can persist for a long period of time,especially in HBV and HCV infection,leading to chronic hepatitis and further progressing to hepatic cirrhosis and liver cancer.HHV infection brings about complications in other organs,and both acute and chronic hepatitis have been associated with clinical presentations outside the liver.Vascular involvement with cutaneous and systemic vasculitis is a well-known extrahepatic presentation;moreover,there is growing evidence for a possible causal relationship between viral pathogens and vasculitis.Except for hepatitis delta virus,other HHVs have participated in the etiopathogenesis of cutaneous and systemic vasculitis via different mechanisms,including direct viral invasion of vascular endothelial cells,immune complex-mediated vessel wall damage,and autoimmune responses with stimulation of autoreactive B-cells and impaired regulatory T-cells.Cryoglobulinemic vasculitis and polyarteritis nodosa are recognized for their association with chronic HHV infection.Although therapeutic guidelines for HHV-associated vasculitis have not yet been established,antiviral therapy should be initiated in HBV and HCV-related systemic vasculitis in addition to the use of corticosteroids.Plasma exchange and/or combined cyclophosphamide and corticosteroid therapy can be considered in patients with severe life-threatening vasculitis manifestations.

Laboratory biosafety for handling emerging viruses

Emerging viruses are viruses whose occurrence has risen within the past twenty years,or whose presence is likely to increase in the near future.Diseases caused by emerging viruses are a major threat to global public health.In spite of greater awareness of safety and containment procedures,the handling of pathogenic viruses remains a likely source of infection,and mortality,among laboratory workers.There is a steady increase in both the number of laboratories and scientist handling emerging viruses for diagnostics and research.The potential for harm associated to work with these infectious agents can be minimized through the application of sound biosafety concepts and practices.The main factors to the prevention of laboratory-acquired infection are well-trained personnel who are knowledgable and biohazard aware,who are perceptive of the various ways of transmission,and who are professional in safe laboratory practice management.In addition,we should emphasize that appropriate facilities,practices and procedures are to be used by the laboratory workers for the handling of emerging viruses in a safe and secure manner.This review is aimed at providing researchers and laboratory personnel with basic biosafety principles to protect themselves from exposure to emerging viruses while working in the laboratory.This paper focuses on what emerging viruses are,why emerging viruses can cause laboratory-acquired infection,how to assess the risk of working with emerging viruses,and how laboratory-acquired infection can be prevented.Control measures used in the laboratory designed as such that they protect workers from emerging viruses and safeguard the public through the safe disposal of infectious wastes are also addressed.

A duplex RT-PCR assay for detection of H9 subtype avian influenza viruses and infectious bronchitis viruses

H9 s ubtype avian influenza virus（AIV） and infectious bronchitis virus（IBV） are major pathogens circulating in poultry and have resulted in great economic losses due to respiratory disease and reduced egg production. As similar symptoms are elicited by the two pathogens, it is difficult for their differential diagnosis. So far, no reverse transcription-polymerase chain reaction（RT-PCR） assay has been found to differentiate between H9 AIV and IBV in one reaction. Therefore, developing a sensitive and specific method is of importance to simultaneously detect and differentiate H9 AIV and IBV. In this study, a duplex RT-PCR（d RT-PCR） was established. Two primer sets target the hemagglutinin（HA） gene of H9 AIV and the nucleocapsid（N） gene of IBV, respectively. Spec ific PCR products were obtained from all tested H9 AIVs and IBVs belonging to the major clades circulating in China, but not from AIVs of other subtypes or other infectious avian viruses. The sensitivity of the d RT-PCR assay corresponding to H9 AIV, IBV and mixture of H9 AIV and IBV were at a concentration of 1×10^1, 1.5×10^1 and 1.5×10^1 50% egg infective doses（EID_（50）） m L^–1, respectively. The concordance rates between the d RT-PCR and virus isolation were 99.1 and 98.2%, respectively, for detection of samples from H9N2 AIV or IBV infected chickens, while the concordance rate was 99.1% for detection of samples from H9N2 AIV and IBV co-infected chickens. Thus, the d RT-PCR assay reported herein is specific and sensitive, and suitable for the differential diagnosis of clinical infections and survei llance of H9 AIVs and IBVs.

Innate and adaptive immune responses against picornaviruses and their counteractions: An overview

Picornaviruses, small positive-stranded RNA viruses, cause a wide range of diseases which is based on their differential tissue and cell type tropisms. This diversity is reflected by the immune responses, both innate and adaptive, induced after infection, and the subsequent interactions of the viruses with the immune system. The defense mechanisms of the host and the countermeasures of the virus significantly contribute to the pathogenesis of the infections. Important human pathogens are poliovirus, coxsackievirus, human rhinovirus and hepatitis A virus. These viruses are the beststudied members of the family, and in this review we want to present the major aspects of the reciprocal effects between the immune system and these viruses.

Physicochemical Properties of Musk Deer Pneumonia and Purulent Disease Viruses

[ Objective] To understand the physicochemical properties of musk deer pneumonia and purulent disease viruses. [ Method] The pneu- monia and purulent disease viruses were isolated from the abnormal and purulent lung tissues of musk deer. Then the isolated viruses were inocula- ted into the Vero cells. After culturing, the virus solution was collected and used to determine TCID50 and genoma types. The sensitivity to fat sol- vent, resistance to hydrochloric acid and trypsin as well as tolerance to heat of the musk deer pneumonia and purulent disease viruses were detec- ted, respectively. [ Result] The obvious cytopathic effects （CPE） were found in Veto cells infected by the isolated viruses. The virus was 2-1.43 TCID50/ml and its genome was RNA. The virus was not sensitive to chloroform, 1% trypsin and heats, and it had a certain tolerance to 0.1 mol/L hy- drochloric acid. [ Conclusion] The study on the physicochemical properties of musk deer pneumonia and purulent disease viruses lays a foundation for prevention and control of the musk deer pneumonia and purulent diseases.

Non-Linear Mathematical Model of the Interaction between Tumor and Oncolytic Viruses

A mathematical modeling of tumor therapy with oncolytic viruses is discussed. The model consists of two coupled, deterministic differential equations allowing for cell reproduction and death, and cell infection. The model is one of the conceptual mathematical models of tumor growth that treat a tumor as a dynamic society of interacting cells. In this paper, we obtain an approximate analytical expression of uninfected and infected cell population by solving the non-linear equations using Homotopy analysis method (HAM). Furthermore, the results are compared with the numerical simulation of the problem using Matlab program. The obtained results are valid for the whole solution domain.

Solar Radiation, Perelman Entropy Mapping, DNA, Viruses etc.

A short note based on the homogeneous 5D space-time topological mappings is extended to cover DNAs of viruses and how the body’s immune system can be enhanced to recognize and remove it.

Synchronous Detection of DNA/RNA of Four Shrimp Viruses by Real-time Fluorescence Quantitative RT-PCR

[ Objective] This study aimed to establish a simultaneous detection method of shrimp viruses by real-time fluorescence quantitative RT-PCR, to improve the efficiency of inspection and quarantine. [ Method] A novel real-time fluorescence quantitative RT-PCR assay was established and optimized for simultaneously detecting DNA/RNA of four shrimp viruses （WSSV, IHHNV, TSV and YHV ）. [ Result] The optimized real-time fluorescence quantitative RT-PCR system gener- ated typical amplification curves with high amplification efficiencies （E = 1.06, 1.07, 0.92 and 0.92, respectively）, good hnear relationship （ r = 1 ）, uniform repeatability （ standard deviation = 0.05 - 0.46 ; variation coefficient = 0.26% - 1.62% ） and high sensitivity, exhibiting no significant differences compared with re- al-time fluorescence quantitative PCR （average error of Ct value = 0.04 -0.40; T = 0.53 -2.50; P 〉 0.05 ）. The total detection time was about 1 h. [ Conclusion] The optimized real-time fluorescence quantitative RT-PCR system can be used for rapid detection of WSSV, IHHNV, TSV and YHV.