2024 Vol.39(4)
Influenza A virus (IAV) possesses a broad host range and undergoes rapid genomic variation, leading to the continuous emergence of novel viruses with significant antigenic variations and cross-species transmission potential. Understanding the evolutionary patterns and underlying mechanisms of all IAVs is crucial for effective prevention and control. However, current genetic clustering methods, such as phylogenetic-based and genetic distance-based approaches, lack phylogenetic information, which hinders the identification of complex events such as reassortments. In this issue, Ding et al. developed a novel genotype identification method, named FluTyping, to enhance the investigation of IAV genotype-based evolution. Based on both genetic distance and phylogenetic relationships, FluTyping established a comprehensive set of classification for all IAVs using whole genome sequences, offering a macro perspective of IAVs' genetic diversity patterns and their restriction factors. The cover image depicts IAVs with multi-genotypes co-circulation patterns show region-specific dominant genotypes, and the restriction of IAV transmission within specific regions contributes to the prevalence of certain genotypes (Kindly designed and provided by Dr. Xiao Ding, Prof. Aiping Wu and Prof. Taijiao Jiang). See page 525–536 for details.
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Transmission restriction and genomic evolution co-shape the genetic diversity patterns of influenza A virus
2024, 39(4): 525 doi: 10.1016/j.virs.2024.02.005
Received: 04 December 2023
Accepted: 22 February 2024
Influenza A virus (IAV) shows an extensive host range and rapid genomic variations, leading to continuous emergence of novel viruses with significant antigenic variations and the potential for cross-species transmission. This causes global pandemics and seasonal flu outbreaks, posing sustained threats worldwide. Thus, studying all IAVs' evolutionary patterns and underlying mechanisms is crucial for effective prevention and control. We developed FluTyping to identify IAV genotypes, to explore overall genetic diversity patterns and their restriction factors. FluTyping groups isolates based on genetic distance and phylogenetic relationships using whole genomes, enabling identification of each isolate's genotype. Three distinct genetic diversity patterns were observed: one genotype domination pattern comprising only H1N1 and H3N2 seasonal influenza subtypes, multi-genotypes co-circulation pattern including majority avian influenza subtypes and swine influenza H1N2, and hybrid-circulation pattern involving H7N9 and three H5 subtypes of influenza viruses. Furthermore, the IAVs in multi-genotypes co-circulation pattern showed region-specific dominant genotypes, implying the restriction of virus transmission is a key factor contributing to distinct genetic diversity patterns, and the genomic evolution underlying different patterns was more influenced by host-specific factors. In summary, a comprehensive picture of the evolutionary patterns of overall IAVs is provided by the FluTyping's identified genotypes, offering important theoretical foundations for future prevention and control of these viruses.
RNA viromes of Dermacentor nuttalli ticks reveal a novel uukuvirus in Qīnghăi Province, China
2024, 39(4): 537 doi: 10.1016/j.virs.2024.04.006
Received: 17 December 2023
Accepted: 23 April 2024
Ticks are a major parasite on the Qīnghăi-Tibet Plateau, western China, and represent an economic burden to agriculture and animal husbandry. Despite research on tick-borne pathogens that threaten humans and animals, the viromes of dominant tick species in this area remain unknown. In this study, we collected Dermacentor nuttalli ticks near Qīnghăi Lake and identified 13 viruses belonging to at least six families through metagenomic sequencing. Four viruses were of high abundance in pools, including Xīnjiāng tick-associated virus 1 (XJTAV1), and three novel viruses: Qīnghăi Lake virus 1, Qīnghăi Lake virus 2 (QHLV1, and QHLV2, unclassified), and Qīnghăi Lake virus 3 (QHLV3, genus Uukuvirus of family Phenuiviridae in order Bunyavirales), which lacks the M segment. The minimum infection rates of the four viruses in the tick groups were 8.2%, 49.5%, 6.2%, and 24.7%, respectively, suggesting the prevalence of these viruses in D. nuttalli ticks. A putative M segment of QHLV3 was identified from the next-generation sequencing data and further characterized for its signal peptide cleavage site, N-glycosylation, and transmembrane region. Furthermore, we probed the L, M, and S segments of other viruses from sequencing data of other tick pools by using the putative M segment sequence of QHLV3. By revealing the viromes of D. nuttalli ticks, this study enhances our understanding of tick-borne viral communities in highland regions. The putative M segment identified in a novel uukuvirus suggests that previously identified uukuviruses without M segments should have had the same genome organization as typical bunyaviruses. These findings will facilitate virus discovery and our understanding of the phylogeny of tick-borne uukuviruses.
Continued evolution of H10N3 influenza virus with adaptive mutations poses an increased threat to mammals
2024, 39(4): 546 doi: 10.1016/j.virs.2024.06.005
Received: 02 January 2024
Accepted: 10 June 2024
The H10 subtype avian influenza virus (AIV) poses an ongoing threat to both birds and humans. Notably, fatal human cases of H10N3 and H10N8 infections have drawn public attention. In 2022, we isolated two H10N3 viruses (A/chicken/Shandong/0101/2022 and A/chicken/Shandong/0603/2022) from diseased chickens in China. Genome analysis revealed that these viruses were genetically associated with human-origin H10N3 virus, with internal genes originating from local H9N2 viruses. Compared to the H10N8 virus (A/chicken/Jiangxi/102/2013), the H10N3 viruses exhibited enhanced thermostability, increased viral release from erythrocytes, and accumulation of hemagglutinin (HA) protein. Additionally, we evaluated the pathogenicity of both H10N3 and H10N8 viruses in mice. We found that viral titers could be detected in the lungs and nasal turbinates of mice infected with the two H10N3 viruses, whereas H10N8 virus titers were detectable in the lungs and brains of mice. Notably, the proportion of double HA Q222R and G228S mutations in H10N3 viruses has increased since 2019. However, the functional roles of the Q222R and G228S double mutations in the HA gene of H10N3 viruses remain unknown and warrant further investigation. Our study highlights the potential public health risk posed by the H10N3 virus. A spillover event of AIV to humans could be a foretaste of a looming pandemic. Therefore, it is imperative to continuously monitor the evolution of the H10N3 influenza virus to ensure targeted prevention and control measures against influenza outbreaks.
Diverse genotypes of norovirus genogroup I and II contamination in environmental water in Thailand during the COVID-19 outbreak from 2020 to 2022
2024, 39(4): 556 doi: 10.1016/j.virs.2024.05.010
Received: 18 December 2023
Accepted: 28 May 2024
Noroviruses (NoVs) are the most significant viral pathogens associated with waterborne and foodborne outbreaks of nonbacterial acute gastroenteritis in humans worldwide. This study aimed to investigate the prevalence and diversity of NoVs contaminated in the environmental water in Chiang Mai, Thailand. A total of 600 environmental water samples were collected from ten sampling sites in Chiang Mai from July 2020 to December 2022. The presence of NoV genogroups I (GI), GII, and GIV were examined using real-time RT-PCR assay. The genotype of the virus was determined by nucleotide sequencing and phylogenetic analysis. The results showed that NoV GI and GII were detected at 8.5% (51/600) and 11.7% (70/600) of the samples tested, respectively. However, NoV GIV was not detected in this study. NoV circulated throughout the year, with a higher detection rate during the winter season. Six NoV GI genotypes (GI.1-GI.6) and eight NoV GII genotypes (GII.2, GII.3, GII.7, GII.8, GII.10, GII.13, GII.17, and GII.21) were identified. Among 121 NoV strains detected, GII.17 was the most predominant genotype (24.8%, 30 strains), followed by GII.2 (21.5%, 26 strains), GI.3 (17.4%, 21 strains), and GI.4 (16.5%, 20 strains). Notably, NoV GII.3, GII.7, GII.8, and GII.10 were detected for the first time in water samples in this area. This study provides insight into the occurrence and seasonal pattern of NoV along with novel findings of NoV strains in environmental water in Thailand during the COVID-19 outbreak. Our findings emphasize the importance of further surveillance studies to monitor viral contamination in environmental water.
Individual virome analysis reveals the general co-infection of mammal-associated viruses with SARS-related coronaviruses in bats
2024, 39(4): 565 doi: 10.1016/j.virs.2024.06.008
Received: 17 April 2024
Accepted: 19 June 2024
Bats are the natural reservoir hosts for SARS-related coronavirus (SARSr-CoV) and other highly pathogenic microorganisms. Therefore, it is conceivable that an individual bat may harbor multiple microbes. However, there is limited knowledge on the overall co-circulation of microorganisms in bats. Here, we conducted a 16-year monitoring of bat viruses in south and central China and identified 238 SARSr-CoV positive samples across nine bat species from ten provinces or administrative districts. Among these, 76 individual samples were selected for further metagenomics analysis. We found a complex microenvironment characterized by the general co-circulation of microbes from two different sources: mammal-associated viruses or environment-associated microbes. The later includes commensal bacteria, enterobacteria-related phages, and insect or fungal viruses of food origin. Results showed that 25% (19/76) of the samples contained at least one another mammal-associated virus, notably alphacoronaviruses (13/76) such as AlphaCoV/YN2012, HKU2-related CoV and AlphaCoV/Rf-HuB2013, along with viruses from other families. Notably, we observed three viruses co-circulating within a single bat, comprising two coronavirus species and one picornavirus. Our analysis also revealed the potential presence of pathogenic bacteria or fungi in bats. Furthermore, we obtained 25 viral genomes from the 76 bat SARSr-CoV positive samples, some of which formed new evolutionary lineages. Collectively, our study reveals the complex microenvironment of bat microbiome, facilitating deeper investigations into their pathogenic potential and the likelihood of cross-species transmission.
NSUN2 mediates distinct pathways to regulate enterovirus 71 replication
2024, 39(4): 574 doi: 10.1016/j.virs.2024.05.002
Received: 03 March 2024
Accepted: 03 April 2024
Increasing evidences suggest that the methyltransferase NSUN2 catalyzes 5-methylcytosine (m5C) modifications on viral RNAs, which are essential for the replication of various viruses. Despite the function of m5C deposition is well characterized, other potential roles of NSUN2 in regulating viral replication remain largely unknown. In this study, the m5C modified residues catalyzed by NSUN2 on enterovirus 71 (EV71) RNAs were mapped. NSUN2, along with m5C modifications, played multiple roles during the EV71 life cycle. Functional m5C modified nucleotides increased the translational efficiency and stability of EV71 RNAs. Additionally, NSUN2 was found to target the viral protein VP1 for binding and promote its stability by inhibiting the ubiquitination. Furthermore, both viral replication and pathogenicity in mice were largely attenuated when functional m5C residues were mutated. Taken together, this study characterizes distinct pathways mediated by NSUN2 in regulating EV71 replication, and highlights the importance of its catalyzed m5C modifications on EV71 RNAs for the viral replication and pathogenicity.
Pseudorabies virus VHS protein abrogates interferon responses by blocking NF-κB and IRF3 nuclear translocation
2024, 39(4): 587 doi: 10.1016/j.virs.2024.05.009
Received: 05 January 2024
Accepted: 23 May 2024
Herpesviruses antagonize host antiviral responses through a myriad of molecular strategies culminating in the death of the host cells. Pseudorabies virus (PRV) is a significant veterinary pathogen in pigs, causing neurological sequalae that ultimately lead to the animal's demise. PRV is known to trigger apoptotic cell death during the late stages of infection. The virion host shutdown protein (VHS) encoded by UL41 plays a crucial role in the PRV infection process. In this study, we demonstrate that UL41 inhibits PRV-induced activation of inflammatory cytokine and negatively regulates the cGAS-STING-mediated antiviral activity by targeting IRF3, thereby inhibiting the translocation and phosphorylation of IRF3. Notably, mutating the conserved amino acid sites (E192, D194, and D195) in the RNase domain of UL41 or knocking down UL41 inhibits the immune evasion of PRV, suggesting that UL41 may play a crucial role in PRV's evasion of the host immune response during infection. These results enhance our understanding of how PRV structural proteins assist the virus in evading the host immune response.
Identification of residues in Lassa virus glycoprotein 1 involved in receptor switch
2024, 39(4): 600 doi: 10.1016/j.virs.2024.06.001
Received: 18 January 2024
Accepted: 31 May 2024
Lassa virus (LASV) is an enveloped, negative-sense RNA virus that causes Lassa hemorrhagic fever. Successful entry of LASV requires the viral glycoprotein 1 (GP1) to undergo a receptor switch from its primary receptor alpha-dystroglycan (α-DG) to its endosomal receptor lysosome-associated membrane protein 1 (LAMP1). A conserved histidine triad in LASV GP1 has been reported to be responsible for receptor switch. To test the hypothesis that other non-conserved residues also contribute to receptor switch, we constructed a series of mutant LASV GP1 proteins and tested them for binding to LAMP1. Four residues, L84, K88, L107, and H170, were identified as critical for receptor switch. Substituting any of the four residues with the corresponding lymphocytic choriomeningitis virus (LCMV) residue (L84 N, K88E, L10F, and H170S) reduced the binding affinity of LASV GP1 for LAMP1. Moreover, all mutations caused decreases in glycoprotein precursor (GPC)-mediated membrane fusion at both pH 4.5 and 5.2. The infectivity of pseudotyped viruses bearing either GPCL84N or GPCK88E decreased sharply in multiple cell types, while L107F and H170S had only mild effects on infectivity. Using biolayer light interferometry assay, we found that all four mutants had decreased binding affinity to LAMP1, in the order of binding affinity being L84 N > L107F > K88E > H170S. The four amino acid loci identified for the first time in this study have important reference significance for the in-depth investigation of the mechanism of receptor switching and immune escape of LASV occurrence and the development of reserve anti-LASV infection drugs.
The binding and structural basis of fox ACE2 to RBDs from different sarbecoviruses
2024, 39(4): 609 doi: 10.1016/j.virs.2024.06.004
Received: 19 March 2024
Accepted: 06 June 2024
Foxes are susceptible to SARS-CoV-2 in laboratory settings, and there have also been reports of natural infections of both SARS-CoV and SARS-CoV-2 in foxes. In this study, we assessed the binding capacities of fox ACE2 to important sarbecoviruses, including SARS-CoV, SARS-CoV-2, and animal-origin SARS-CoV-2 related viruses. Our findings demonstrated that fox ACE2 exhibits broad binding capabilities to receptor-binding domains (RBDs) of sarbecoviruses. We further determined the cryo-EM structures of fox ACE2 complexed with RBDs of SARS-CoV, SARS-CoV-2 prototype (PT), and Omicron BF.7. Through structural analysis, we identified that the K417 mutation can weaken the ability of SARS-CoV-2 sub-variants to bind to fox ACE2, thereby reducing the susceptibility of foxes to SARS-CoV-2 sub-variants. In addition, the Y498 residue in the SARS-CoV RBD plays a crucial role in forming a vital cation-π interaction with K353 in the fox ACE2 receptor. This interaction is the primary determinant for the higher affinity of the SARS-CoV RBD compared to that of the SARS-CoV-2 PT RBD. These results indicate that foxes serve as potential hosts for numerous sarbecoviruses, highlighting the critical importance of surveillance efforts.
Structural and functional insights into the 2'-O-methyltransferase of SARS-CoV-2
2024, 39(4): 619 doi: 10.1016/j.virs.2024.07.001
Received: 24 November 2023
Accepted: 02 July 2024
A unique feature of coronaviruses is their utilization of self-encoded nonstructural protein 16 (nsp16), 2'-O-methyltransferase (2'-O-MTase), to cap their RNAs through ribose 2'-O-methylation modification. This process is crucial for maintaining viral genome stability, facilitating efficient translation, and enabling immune escape. Despite considerable advances in the ultrastructure of SARS-CoV-2 nsp16/nsp10, insights into its molecular mechanism have so far been limited. In this study, we systematically characterized the 2'-O-MTase activity of nsp16 in SARS-CoV-2, focusing on its dependence on nsp10 stimulation. We observed cross-reactivity between nsp16 and nsp10 in various coronaviruses due to a conserved interaction interface. However, a single residue substitution (K58T) in SARS-CoV-2 nsp10 restricted the functional activation of MERS-CoV nsp16. Furthermore, the cofactor nsp10 effectively enhanced the binding of nsp16 to the substrate RNA and the methyl donor S-adenosyl-l-methionine (SAM). Mechanistically, His-80, Lys-93, and Gly-94 of nsp10 interacted with Asp-102, Ser-105, and Asp-106 of nsp16, respectively, thereby effectively stabilizing the SAM binding pocket. Lys-43 of nsp10 interacted with Lys-38 and Gly-39 of nsp16 to dynamically regulate the RNA binding pocket and facilitate precise binding of RNA to the nsp16/nsp10 complex. By assessing the conformational epitopes of nsp16/nsp10 complex, we further determined the critical residues involved in 2'-O-MTase activity. Additionally, we utilized an in vitro biochemical platform to screen potential inhibitors targeting 2'-O-MTase activity. Overall, our results significantly enhance the understanding of viral 2'-O methylation process and mechanism, providing valuable targets for antiviral drug development.
AIMP2 restricts EV71 replication by recruiting SMURF2 to promote the degradation of 3D polymerase
2024, 39(4): 632 doi: 10.1016/j.virs.2024.06.009
Received: 19 March 2024
Accepted: 25 June 2024
Hand, foot and mouth disease (HFMD), mainly caused by enterovirus 71 (EV71), has frequently occurred in the Asia-Pacific region, posing a significant threat to the health of infants and young children. Therefore, research on the infection mechanism and pathogenicity of enteroviruses is increasingly becoming important. The 3D polymerase, as the most critical RNA-dependent RNA polymerase (RdRp) for EV71 replication, is widely targeted to inhibit EV71 infection. In this study, we identified a novel host protein, AIMP2, capable of binding to 3D polymerase and inhibiting EV71 infection. Subsequent investigations revealed that AIMP2 recruits the E3 ligase SMURF2, which mediates the polyubiquitination and degradation of 3D polymerase. Furthermore, the antiviral effect of AIMP2 extended to the CVA16 and CVB1 serotypes. Our research has uncovered the dynamic regulatory function of AIMP2 during EV71 infection, revealing a novel antiviral mechanism and providing new insights for the development of antienteroviral therapeutic strategies.
Design of antiviral AGO2-dependent short hairpin RNAs
2024, 39(4): 645 doi: 10.1016/j.virs.2024.05.001
Received: 11 March 2024
Accepted: 06 May 2024
The increasing emergence and re-emergence of RNA virus outbreaks underlines the urgent need to develop effective antivirals. RNA interference (RNAi) is a sequence-specific gene silencing mechanism that is triggered by small interfering RNAs (siRNAs) or short hairpin RNAs (shRNAs), which exhibits significant promise for antiviral therapy. AGO2-dependent shRNA (agshRNA) generates a single-stranded guide RNA and presents significant advantages over traditional siRNA and shRNA. In this study, we applied a logistic regression algorithm to a previously published chemically siRNA efficacy dataset and built a machine learning-based model with high predictive power. Using this model, we designed siRNA sequences targeting diverse RNA viruses, including human enterovirus A71 (EV71), Zika virus (ZIKV), dengue virus 2 (DENV2), mouse hepatitis virus (MHV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and transformed them into agshRNAs. We validated the performance of our agshRNA design by evaluating antiviral efficacies of agshRNAs in cells infected with different viruses. Using the agshRNA targeting EV71 as an example, we showed that the anti-EV71 effect of agshRNA was more potent compared with the corresponding siRNA and shRNA. Moreover, the antiviral effect of agshRNA is dependent on AGO2-processed guide RNA, which can load into the RNA-induced silencing complex (RISC). We also confirmed the antiviral effect of agshRNA in vivo. Together, this work develops a novel antiviral strategy that combines machine learning-based algorithm with agshRNA design to custom design antiviral agshRNAs with high efficiency.
Detection of HBV DNA integration in plasma cell-free DNA of different HBV diseases utilizing DNA capture strategy
2024, 39(4): 655 doi: 10.1016/j.virs.2024.06.003
Received: 24 January 2024
Accepted: 04 June 2024
The landscape of hepatitis B virus (HBV) integration in the plasma cell-free DNA (cfDNA) of HBV-infected patients with different stages of liver diseases [chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC)] remains unclear. In this study, we developed an improved strategy for detecting HBV DNA integration in plasma cfDNA, based on DNA probe capture and next-generation sequencing. Using this optimized strategy, we successfully detected HBV integration events in chimeric artificial DNA samples and HBV-infected HepG2-NTCP cells at day one post infection, with high sensitivity and accuracy. The characteristics of HBV integration events in the HBV-infected HepG2-NTCP cells and plasma cfDNA from HBV-infected individuals (CHB, LC, and HCC) were further investigated. A total of 112 and 333 integration breakpoints were detected in the HepG2-NTCP cells and 22 out of 25 (88%) clinical HBV-infected samples, respectively. In vivo analysis showed that the normalized number of support unique sequences (nnsus) in HCC was significantly higher than in CHB or LC patients (P values < 0.05). All integration breakpoints are randomly distributed on human chromosomes and are enriched in the HBV genome around nt 1800. The majority of integration breakpoints (61.86%) are located in the gene-coding region. Both non-homologous end-joining (NHEJ) and microhomology-mediated end-joining (MMEJ) interactions occurred during HBV integration across the three different stages of liver diseases. Our study provides evidence that HBV DNA integration can be detected in the plasma cfDNA of HBV-infected patients, including those with CHB, LC, or HCC, using this optimized strategy.
Measures of insulin resistance and beta cell function before and after treatment of HCV infection
2024, 39(4): 667 doi: 10.1016/j.virs.2024.06.007
Received: 31 December 2023
Accepted: 19 June 2024
The association between chronic HCV infection and type 2 diabetes mellitus (T2DM) has been established; however, there is limited research on β-cell function particularly in the pre-diabetic population. Here, we evaluated indices of β-cell function and insulin sensitivity across the spectrum from normal glucose tolerance to T2DM in individuals with and without chronic hepatitis C (CHC), and the effects of antiviral treatments on these variables. A total of 153 non-cirrhotic, non-fibrotic CHC patients with a BMI <25 were enrolled in the study. Among them, 119 were successfully treated with either direct acting antiviral (DAA) drugs or pegylated interferon/ribavirin (IFN/RBV) anti-HCV therapy. Fasting state- and oral glucose tolerance test (OGTT)-derived indexes were used to evaluate β-cell function and insulin sensitivity. Among all subjects, 19 (13%) had T2DM and 21% exhibited pre-diabetes including 8% isolated impaired fasting glucose (IFG) and 13% combined IFG and impaired glucose tolerance (IGT). Early and total insulin secretion adjusted for the degree of insulin resistance were decreased in pre-diabetic CHC patients compared to HCV-uninfected individuals. Viral eradication through DAA or IFN/RBV therapy demonstrated positive impacts on insulin sensitivity and β-cell function in CHC patients who achieved sustained virologic response (SVR), regardless of fasting or OGTT state. These findings emphasize the role of HCV in the development of β-cell dysfunction, while also suggesting that viral eradication can improve insulin secretion, reverse insulin resistance, and ameliorate glycemic control. These results have important implications for managing pre-diabetic CHC patients and could prevent diabetes-related clinical manifestations and complications.
A quadrivalent norovirus vaccine based on a chimpanzee adenovirus vector induces potent immunity in mice
2024, 39(4): 675 doi: 10.1016/j.virs.2024.07.002
Received: 20 November 2023
Accepted: 08 July 2024
Norovirus (NoV) infection is a major cause of gastroenteritis worldwide. The virus poses great challenges in developing vaccines with broad immune protection due to its genetic and antigenic diversity. To date, there are no approved NoV vaccines for clinical use. Here, we aimed to develop a broad-acting quadrivalent NoV vaccine based on a chimpanzee adenovirus vector, AdC68, carrying the major capsid protein (VP1) of noroviral GI and GII genotypes. Compared to intramuscular (i.m.), intranasal (i.n.), or other prime-boost immunization regimens (i.m. + i.m., i.m. + i.n., i.n. + i.m.), AdC68-GI.1-GII.3 (E1)-GII.4-GII.17 (E3), administered via i.n. + i.n. induced higher titers of serum IgG antibodies and higher IgA antibodies in bronchoalveolar lavage fluid (BALF) and saliva against the four homologous VP1s in mice. It also significantly stimulated the production of blocking antibodies against the four genotypes. In response to re-stimulation with virus-like particles (VLP)-GI.1, VLP-GII.3, VLP-GII.4, and VLP-GII.17, the quadrivalent vaccine administered according to the i.n. + i.n. regimen effectively triggered specific cell-mediated immune responses, primarily characterized by IFN-γ secretion. Furthermore, the preparation of this novel quadrivalent NoV vaccine requires only a single recombinant adenovirus to provide broad preventive immunity against the major GI/GII epidemic strains, making it a promising vaccine candidate for further development.
Baicalein suppresses Coxsackievirus B3 replication by inhibiting caspase-1 and viral protease 2A
2024, 39(4): 685 doi: 10.1016/j.virs.2024.07.003
Received: 09 January 2024
Accepted: 12 July 2024
Myocarditis is an inflammatory disease of the cardiac muscle and one of the primary causes of dilated cardiomyopathy. Group B coxsackievirus (CVB) is one of the leading causative pathogens of viral myocarditis, which primarily affects children and young adults. Due to the lack of vaccines, the development of antiviral medicines is crucial to controlling CVB infection and the progression of myocarditis. In this study, we investigated the antiviral effect of baicalein, a flavonoid extracted from Scutellaria baicaleinsis. Our results demonstrated that baicalein treatment significantly reduced cytopathic effect and increased cell viability in CVB3-infected cells. In addition, significant reductions in viral protein 3D, viral RNA, and viral particles were observed in CVB3-infected cells treated with baicalein. We found that baicalein exerted its inhibitory effect in the early stages of CVB3 infection. Baicalein also suppressed viral replication in the myocardium and effectively alleviated myocarditis induced by CVB3 infection. Our study revealed that baicalein exerts its antiviral effect by inhibiting the activity of caspase-1 and viral protease 2A. Taken together, our findings demonstrate that baicalein has antiviral activity against CVB3 infection and may serve as a potential therapeutic option for the myocarditis caused by enterovirus infection.
Seroprevalence of neutralizing antibodies against HFMD associated enteroviruses among healthy individuals in Shanghai, China, 2022
2024, 39(4): 694 doi: 10.1016/j.virs.2024.05.008
Received: 20 October 2023
Accepted: 20 May 2024
Highlights1. The first report of serological characteristics of HFMD associated enteroviruses in Shanghai after the COVID-19 epidemic.2. The seroprevalence of protective NtAbs against Coxsackieviruses was low within the susceptible population of HFMD.3. The presence of a silent outbreak and circulation of CVA4 was confirmed among elderly individuals.
Correlation between circulating T follicular helper cell levels after infection and a decreased risk of COVID-19 re-infection
2024, 39(4): 699 doi: 10.1016/j.virs.2024.06.002
Received: 25 January 2024
Accepted: 30 May 2024
Highlights1. Our study conducted a retrospective analysis of individuals with differing susceptibilities to COVID-19.2. The correlation between cTfh cells and neutralizing antibodies enhances protection against SARS-CoV-2.3. cTfh cell responses are positively associated with a decreased risk of SARS-CoV-2 reinfection.
First complete genomic sequence analysis of canine distemper virus in wild boar
2024, 39(4): 702 doi: 10.1016/j.virs.2024.05.004
Received: 25 October 2023
Accepted: 29 March 2024
Highlights1. The first complete genomic sequence of canine distemper virus from wild boar in northeast China was obtained.2. Phylogenetic analysis showed that this wild boar CDV strain belongs to the Arctic lineage.3. Wild boars in northeast China have detectable level of anti-CDV neutralizing antibodies, with a positive percentage of 18.3% (11/60).
Coexistence of adeno-associated virus 2 with adenovirus 18 or herpesvirus may be associated with severe lingual papillomatosis in an immunocompromised individual
2024, 39(4): 705 doi: 10.1016/j.virs.2024.06.006
Received: 16 October 2023
Accepted: 19 June 2024
Highlights
1. Viral metagenomics analysis was conducted on samples from an HSCT recipient experiencing severe lingual papillomatosis.
2. Coexistence of AAV2 with AdV18 in fecal and HSV-1 in tissue samples was detected.
3. A second complete genome of AdV18 was obtained in this study and is available in public databases.
1. Viral metagenomics analysis was conducted on samples from an HSCT recipient experiencing severe lingual papillomatosis.
2. Coexistence of AAV2 with AdV18 in fecal and HSV-1 in tissue samples was detected.
3. A second complete genome of AdV18 was obtained in this study and is available in public databases.
