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Abstract The Qinghai-Tibet Plateau (QTP), renowned for its exceptional biological diversity, is home to numerous endemic species. However, research on the virology of vulnerable vertebrates like yaks remains limited. In this study, our objective was to use metagenomics to provide a comprehensive understanding of the diversity and evolution of the gut virome in yak populations across different regions of the QTP. Our findings revealed a remarkably diverse array of viruses in the gut of yaks, including those associated with vertebrates and bacteriophages. Notably, some vertebrate-associated viruses, such as astrovirus and picornavirus, showed significant sequence identity across diverse yak populations. Additionally, we observed differences in the functional profiles of genes carried by the yak gut virome across different regions. Moreover, the virus-bacterium symbiotic network that we discovered holds potential significance in maintaining the health of yaks. Overall, this research expands our understanding of the viral communities in the gut of yaks and highlights the importance of further investigating the interactions between viruses and their hosts. These data will be beneficial for revealing the crucial role that viruses play in the yak gut ecology in future studies.

Abstract Background The genetic diversity of yak, a key domestic animal on the Qinghai-Tibetan Plateau (QTP), is a vital resource for domestication and breeding efforts. This study presents the first yak pangenome obtained through the de novo assembly of 16 yak genomes. Results We discovered 290 Mb of nonreference sequences and 504 new genes. Our pangenome-wide presence and absence variation (PAV) analysis revealed 5,120 PAV-related genes, highlighting a wide range of variety-specific genes and genes with varying frequencies across yak populations. Principal component analysis (PCA) based on binary gene PAV data classified yaks into three new groups: wild, domestic, and Jinchuan. Moreover, we proposed a ‘two-haplotype genomic hybridization model’ for understanding the hybridization patterns among breeds by integrating gene frequency, heterozygosity, and gene PAV data. A gene PAV-GWAS identified a novel gene (BosGru3G009179) that may be associated with the multirib trait in Jinchuan yaks. Furthermore, an integrated transcriptome and pangenome analysis highlighted the significant differences in the expression of core genes and the mutational burden of differentially expressed genes between yaks from high and low altitudes. Transcriptome analysis across multiple species revealed that yaks have the most unique differentially expressed mRNAs and lncRNAs (between high- and low-altitude regions), especially in the heart and lungs, when comparing high- and low-altitude adaptations. Conclusions The yak pangenome offers a comprehensive resource and new insights for functional genomic studies, supporting future biological research and breeding strategies.

ABSTRACT The diversity of birds in most parts of the world is very high, and thus, they may carry different types of highly differentiated and unknown viruses. Thanks to advanced sequencing technologies, studies on the diversity of bird-associated viruses have increased over the past few years. In this study, a large-scale viral metagenomics survey was performed on cloacal swabs of 2,990 birds from nine provinces of the Chinese mainland. To detect undescribed RNA viruses in birds, more than 1,800 sequences sharing relatively low (

Due to the extensive genetic and antigenic variation in Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), as well as its rapid mutability and evolution, PRRS prevention and control can be challenging. An expeditious and sensitive neutralization assay for PRRSV is presented to monitor neutralizing antibodies (NAbs) in serum during vaccine research. Here, a PRRSV expressing eGFP was successfully rescued with reverse genetics based on the infectious clone HuN4-F112-eGFP which we constructed. The fluorescent protein expressions of the reporter viruses remained stable for at least five passages. Based on this reporter virus, the neutralization assay can be easily used to evaluate the level of NAbs by counting cells with green fluorescence. Compared with the classical CPE assay, the newly developed assay increases sensitivity by one- to four-fold at the early antibody response stage, thus saving 2 days of assay waiting time. By using this assay to unveil the dynamics of neutralizing antibodies against PRRSV, priming immunity through either a single virulent challenge or only vaccination could produce limited NAbs, but re-infection with PRRSV would induce a faster and stronger NAb response. Overall, the novel HuN4-F112-eGFP-based neutralization assay holds the potential to provide a highly efficient platform for evaluating the next generation of PRRS vaccines.

The enteric virome, comprising a complex community of viruses inhabiting the gastrointestinal tract, plays a significant role in health and disease dynamics. In this study, the fecal sample of a wild snow leopard was subjected to viral metagenomic analysis using a double barcode Illumina MiSeq platform. The resulting reads were de novo assembled into contigs with SOAPdenovo2 version r240. Additional bioinformatic analysis of the assembled genome and genome annotation was done using the Geneious prime software (version 2022.0.2). Following viral metagenomic analysis and bioinformatic analysis, a total of 7 viral families and a novel specie of bocaparvovirus tentatively named Panthera uncia bocaparvovirus (PuBOV) with GenBank accession number OQ627713 were identified. The complete genome of PuBOV was predicted to contain 3 open reading frames (ORFs), contains 5433 nucleotides and has a G + C content of 47.40 %. BLASTx analysis and pairwise sequence comparison indicated the novel virus genome was a new species in the genus Bocaparvovirus based on the species demarcation criteria of the International Committee on the Taxonomy of Viruses. This study provides valuable insights into the diversity and composition of the enteric virome in wild endangered snow leopards. The identification and characterization of viruses in wildlife is crucial for developing effective strategies to manage and mitigate potential zoonotic and other viral disease threats to human and animal health.

Pigs are natural host to various zoonotic pathogens including viruses. In this study, we analyzed the viral communities in the feces of 89 piglets with diarrhea under one month old which were collected from six farms in Jiangsu Province of the Eastern China, using the unbiased virus metagenomic method. A total of 89 libraries were constructed, and 46937894 unique sequence reads were generated by Illumina sequencing. Overall, the family Picornaviridae accounted for the majority of the total reads of putative mammalian viruses. Ten novel virus genomes from different family members were discovered, including Parvoviridae (n = 2), Picobirnaviridae (n = 4) and CRESS DNA viruses (n = 4). A large number of phages were identified, which mainly belonged to the order Caudovirales and the family Microviridae. Moreover, some identified viruses were closely related to viruses found in non-porcine hosts, highlighting the potential for cross-species virus dissemination. This study increased our understanding of the fecal virus communities of diarrhea piglets and provided valuable information for virus monitoring and preventing.

Abstract Background Mammals are potential hosts for many infectious diseases. However, studies on the viral communities of herbivorous mammals in the Northwest Plateau are limited. Here, we studied the viral communities of herbivorous mammals in the Northwest Plateau using virus metagenomic analysis to analyze and compare the viral community composition of seven animal species. Results By library construction and next-generation sequencing, contigs and singlets reads with similar viral sequences were classified into 24 viral families. Analyzed from the perspective of sampling areas, the virus community composition was relatively similar in two areas of Wuwei and Jinchang, Gansu Province. Analyzed from the perspective of seven animal species, the viral reads of seven animal species were mostly ssDNA and dominated by CRESS-DNA viruses. Phylogenetic analysis based on viral marker genes indicated that CRESS-DNA viruses and microviruses have high genetic diversity. In addition to DNA viruses, nodaviruses, pepper mild mottle viruses and picornaviruses were RNA viruses that we performed by phylogenetic analysis. The CRESS-DNA viruses and nodaviruses are believed to infect plants and insects, and microviruses can infect bacteria, identifying that they were likely from the diet of herbivorous mammals. Notably, two picornaviruses were identified from red deer and wild horse, showing that the picornavirus found in red deer had the relatively high similarity with human hepatitis A virus, and the picornavirus carried by wild horse could potentially form a new species within the Picornaviridae family. Conclusions This study explored the herbivorous mammalian virus community in the Northwest Plateau and the genetic characteristics of viruses that potentially threaten human health. It reveals the diversity and stability of herbivorous mammalian virus communities in the Northwest Plateau and helps to expand our knowledge of various herbivorous mammalian potentially pathogenic viruses.

Abstract Background Porcine circovirus type 2 (PCV2) has caused great economic losses in the global pig industry. There have been published records of wild rats acting as the reservoirs of PCV2 (only PCV2a and PCV2b), but almost all of which were related to the PCV2-infected swine herds. Results In this study, we carried out the detection, amplification, and characterization of novel PCV2 strains in wild rats that were captured far from pig farms. Nested PCR assay demonstrated that the kidney, heart, lung, liver, pancreas, and large and small intestines of rats were screened positive for PCV2. We subsequently sequenced two full genomes of PCV2 in positive sample pools, designated as js2021-Rt001 and js2021-Rt002. Genome sequence analysis indicated that they had the highest similarity to nucleotide sequences of porcine-origin PCV2 isolates in Vietnam. Phylogenetically, js2021-Rt001 and js2021-Rt002 were a part of the PCV2d genotype cluster, which is a predominant genotype circulating worldwide in recent years. The antibody recognition regions, immunodominant decoy epitope, and heparin sulfate binding motif of the two complete genome sequences coincided with those previously reported. Conclusions Our research reported the genomic characterization of two novel PCV2 strains (js2021-Rt001 and js2021-Rt002) and provided the first supported evidence that PCV2d could naturally infect wild rats in China. However, whether the newly identified strains have potential for circulating in nature in vertical and horizontal transmission or inter-species jumping between rats and pigs needs further research.

ABSTRACT The majority of currently emerging infectious illnesses are zoonotic infections, which have caused serious public health and economic implications. The development of viral metagenomics has helped us to explore unknown viruses. We collected 1,970 canine feces from Yushu and Guoluo in the plateau region of China for this study to do a metagenomics analysis of the viral community of the canine digestive tract. Our analysis identified 203 novel viruses, classified into 11 known families and 2 unclassified groups. These viruses include the hepatitis E virus, first identified in dogs, and the astrovirus, coronavirus, polyomavirus, and others. The relationship between the newly identified canine viruses and known viruses was investigated through the use of phylogenetic analysis. Furthermore, we demonstrated the cross-species transmission of viruses and predicted new viruses that may cause diseases in both humans and animals, providing technical support for the prevention and control of diseases caused by environmental pollution viruses. IMPORTANCE Most emerging infectious diseases are due to zoonotic disease agents. Because of their effects on the security of human or animal life, agriculture production, and food safety, zoonotic illnesses and livestock diseases are of worldwide significance. Because dogs are closely related to humans and domestic animals, they serve as one of the important links in the transmission of zoonotic and livestock diseases. Canines can contaminate the environment in which humans live such as water and soil through secretions, potentially altering the human gut microbiota or causing diseases. Our study enriched the viral community in the digestive tract microbiome of dogs and found types of viruses that threaten human health, providing technical support for the prevention and control of early warning of diseases caused by environmental contaminant viruses.

Abstract Background Since viral metagenomic approach was applied to discover plant viruses for the first time in 2006, many plant viruses had been identified from cultivated and non-cultivated plants. These previous researches exposed that the viral communities (virome) of plants have still largely uncharacterized. Here, we investigated the virome in 161 species belonging to 38 plant orders found in a riverside ecosystem. Results We identified 245 distinct plant-associated virus genomes (88 DNA and 157 RNA viruses) belonging to 27 known viral families, orders, or unclassified virus groups. Some viral genomes were sufficiently divergent to comprise new species, genera, families, or even orders. Some groups of viruses were detected that currently are only known to infect organisms other than plants. It indicates a wider host range for members of these clades than previously recognized theoretically. We cannot rule out that some viruses could be from plant contaminating organisms, although some methods were taken to get rid of them as much as possible. The same viral species could be found in different plants and co-infections were common. Conclusions Our data describe a complex viral community within a single plant ecosystem and expand our understanding of plant-associated viral diversity and their possible host ranges.

ABSTRACT The gut flora is a treasure house of diverse bacteriophages maintaining a harmonious and coexistent relationship with their hosts. The giant panda (Ailuropoda melanoleuca), as a vulnerable endemic species in China, has existed for millions of years and is regarded as a flagship species for biodiversity conservation. And yet, limited studies have analyzed the phage communities in the gut of giant pandas. Using viral metagenomic analysis, the phageomes of giant pandas and other relative species were investigated. Our study explored and compared the composition of phage communities from different animal sources. Giant pandas possessed more diverse and abundant phage communities in the gut compared with other relevant animals. Phylogenetic analyses based on the phage terminase large subunit (TerL) showed that the Caudovirales phages in giant pandas also presented highly genetic diversity. Our study revealed the diversity of phage communities in giant pandas and other relative species, contributing to the health maintenance of giant pandas and laying the groundwork for molecular evolution research of bacteriophages in mammals. IMPORTANCE Gut phageome plays an important role in shaping gut microbiomes by direct interactions with bacteria or indirect influences on the host immune system, potentially regulating host health and disease status. The giant panda (Ailuropoda melanoleuca) is a vulnerable and umbrella species for biodiversity conservation. Our work explored and compared the gut phageome of giant pandas and relative species, contributing to the health maintenance of giant pandas.

Viral diseases caused by new outbreaks of viral infections pose a serious threat to human health. Wild brown rats (Rattus norvegicus), considered one of the world's largest and most widely distributed rodents, are host to various zoonotic pathogens. To further understand the composition of the virus community in wild brown rats and explore new types of potentially pathogenic viruses, viral metagenomics was conducted to investigate blood, feces, and various tissues of wild brown rats captured from Zhenjiang, China. Results indicated that the composition of the virus community in different samples showed significant differences. In blood and tissue samples, members of the Parvoviridae and Anelloviridae form the main body of the virus community. Picornaviridae, Picobirnaviridae, and Astroviridae made up a large proportion of fecal samples. Several novel genome sequences from members of different families, including Anelloviridae, Parvoviridae, and CRESS DNA viruses, were detected in both blood and other samples, suggesting that they have the potential to spread across organs to cause viremia. These viruses included not only strains closely related to human viruses, but also a potential recombinant virus. Multiple dual-segment picornaviruses were obtained from fecal samples, as well as virus sequences from the Astroviridae and Picornaviridae. Phylogenetic analysis showed that these viruses belonged to different genera, with multiple viruses clustered with other animal viruses. Whether they have pathogenicity and the ability to spread across species needs further study.

ABSTRACT Aquaculture is important for food security and nutrition. The economy has recently been significantly threatened and the risk of zoonoses significantly increased by aquatic diseases, and the ongoing introduction of new aquatic pathogens, particularly viruses, continues to represent a hazard. Yet, our knowledge of the diversity and abundance of fish viruses is still limited. Here, we conducted a metagenomic survey of different species of healthy fishes caught in the Lhasa River, Tibet, China, and sampled intestinal contents, gills, and tissues. To be more precise, by identifying and analyzing viral genomes, we aim to determine the abundance, diversity, and evolutionary relationships of viruses in fish with other potential hosts. Our analysis identified 28 potentially novel viruses, 22 of which may be associated with vertebrates, across seven viral families. During our research, we found several new strains of viruses in fish, including papillomavirus, hepadnavirus, and hepevirus. Additionally, we discovered two viral families, Circoviridae and Parvoviridae, which were prevalent and closely related to viruses that infect mammals. These findings further expand our understanding of highland fish viruses and highlight the emerging view that fish harbor large, unknown viruses. IMPORTANCE The economy and zoonoses have recently been significantly threatened by aquatic diseases. Yet, our knowledge of the diversity and abundance of fish viruses is still limited. We identified the wide genetic diversity of viruses that these fish were harboring. Since there are currently few studies on the virome of fish living in the Tibet highland, our research adds to the body of knowledge. This discovery lays the groundwork for future studies on the virome of fish species and other highland animals, preserving the ecological equilibrium on the plateau.

African swine fever is a highly lethal contagious disease of pigs for which there is no vaccine. Its causative agent African swine fever virus (ASFV) is a highly complex enveloped DNA virus encoding more than 150 open reading frames. The antigenicity of ASFV is still unclear at present. In this study, 35 proteins of ASFV were expressed by Escherichia coli, and ELISA was developed for the detection of antibodies against these proteins. p30, p54, and p22 were presented as the major antigens of ASFV, positively reacting with all five clinical ASFV-positive pig sera, and 10 pig sera experimentally infected by ASFV. Five proteins (pB475L, pC129R, pE199L, pE184L, and pK145R) reacted well with ASFV-positive sera. The p30 induced a rapid and strong antibody immune response during ASFV infection. These results will promote the development of subunit vaccines and serum diagnostic methods against ASFV.

African swine fever, which is induced by the African swine fever virus (ASFV), poses a significant threat to the global pig industry due to its high lethality in domestic pigs and wild boars. Despite the severity of the disease, there is a lack of effective vaccines and drugs against the ASFV. The p72 protein, constituting 31 to 33% of the total virus particle mass, serves as the primary capsid protein of ASFV. It is a crucial antigen for the development of ASF subunit vaccines and serological diagnostic methods. In this investigation, 27 monoclonal antibodies (mAbs) were generated through mouse immunization with the truncated C-terminal p72 protein expressed by Escherichia coli. Among these, six mAbs exhibited binding to the p72 trimer, with their respective recognized epitopes identified as 542VTAHGINLIDKF553, 568GNAIKTP574, and 584FALKPREEY592. All three epitopes were situated within the interval sequences of functional units of the C-terminal jelly-roll barrel of p72. Notably, two epitopes, 568GNAIKTP574 and 584FALKPREEY592, were internal to the p72 trimer, while the epitope 542VTAHGINLIDKF553 was exposed on the surface of the trimer and consistently conserved across all ASFV genotypes. These findings enhance our comprehension of the antigenic function and structure of the p72 protein, facilitating the utilization of p72 in the development of diagnostic techniques for ASFV.

Abstract Background Wild birds may harbor and transmit viruses that are potentially pathogenic to humans, domestic animals, and other wildlife. Results Using the viral metagenomic approach, we investigated the virome of cloacal swab specimens collected from 3182 birds (the majority of them wild species) consisting of > 87 different species in 10 different orders within the Aves classes. The virus diversity in wild birds was higher than that in breeding birds. We acquired 707 viral genomes from 18 defined families and 4 unclassified virus groups, with 265 virus genomes sharing < 60% protein sequence identities with their best matches in GenBank comprising new virus families, genera, or species. RNA viruses containing the conserved RdRp domain with no phylogenetic affinity to currently defined virus families existed in different bird species. Genomes of the astrovirus, picornavirus, coronavirus, calicivirus, parvovirus, circovirus, retrovirus, and adenovirus families which include known avian pathogens were fully characterized. Putative cross-species transmissions were observed with viruses in wild birds showing > 95% amino acid sequence identity to previously reported viruses in domestic poultry. Genomic recombination was observed for some genomes showing discordant phylogenies based on structural and non-structural regions. Mapping the next-generation sequencing (NGS) data respectively against the 707 genomes revealed that these viruses showed distribution pattern differences among birds with different habitats (breeding or wild), orders, and sampling sites but no significant differences between birds with different behavioral features (migratory and resident). Conclusions The existence of a highly diverse virome highlights the challenges in elucidating the evolution, etiology, and ecology of viruses in wild birds. Video Abstract

ABSTRACT Tick infestations have been reported as one of the factors threatening the health of giant pandas, but studies of viral pathogens carried by ticks feeding on the blood of giant pandas are limited. To assess whether blood-sucking ticks of giant pandas can carry viral pathogens and if so, whether the viruses in ticks are associated with those previously detected in giant panda hosts, we determined the viromes of ticks detached from giant pandas in a field stocking area in Sichuan Province, southwest China. Using viral metagenomics we identified 32 viral species in ticks, half of which (including anellovirus [n = 9], circovirus [n = 3], and gemycircularvirus [n = 4]) showed homology to viruses carried by giant pandas and their associated host species (such as red pandas and mosquitoes) in the same living domain. Remarkably, several viruses in this study phylogenetically assigned as bunyavirus, hepe-like virus, and circovirus were detected with relatively high abundance, but whether these newly identified tick-associated viruses can replicate in ticks and then transmit to host animals during a blood meal will require further investigation. These findings further expand our understanding of the role of giant panda-infesting ticks in the local ecosystem, especially related to viral acquisition and transmission, and lay a foundation to assess the risk for giant panda exposure to tick-borne viruses. IMPORTANCE Ticks rank only second to mosquitoes as blood-feeding arthropods, capable of spreading pathogens (including viruses, bacteria, and parasites) to hosts during a blood meal. To better understand the relationship between viruses carried by ticks and viruses that have been reported in giant pandas, it is necessary to analyze the viromes of giant panda-parasitic blood-sucking ticks. This study collected 421 ticks on the body surface of giant pandas in Sichuan Province, China. We characterized the extensive genetic diversity of viruses harbored by these ticks and reported frequent communication of viruses between giant pandas and their ticks. While most of the virome discovered here are nonpathogenic viruses from giant pandas and potentially tick-specific viruses, we revealed some possible tick-borne viruses, represented by novel bunyaviruses. This research contributes to the literature because currently there are few studies on the virome of giant panda-infesting ticks.

ABSTRACT The gut virome is a reservoir of diverse symbiotic and pathogenic viruses coevolving with their hosts, and yet limited research has explored the gut viromes of highland-dwelling rare species. Using viral metagenomic analysis, the viral communities of the Phrynocephalus lizards living in the Qinghai-Tibet Plateau were investigated. Phage-encoded functional genes and antibiotic resistance genes (ARGs) were analyzed. The viral communities of different lizard species were all predominated by bacteriophages, especially the Caudovirales order. The virome of Phrynocephalus erythrurus living around the Namtso Lake possessed a unique structure, with the greatest abundance of the Parvoviridae family and the highest number of exclusive viral species. Several vertebrate-infecting viruses were discovered, including caliciviruses, astroviruses, and parvoviruses. Phylogenetic analyses demonstrated that the virus hallmark genes of bacteriophages possessed high genetic diversity. After functional annotation, the majority of phage-associated functional genes were classified in the energy metabolism category. In addition, plenty of ARGs belonging to the multidrug category were discovered, and five ARGs were exclusive to the virome from Phrynocephalus theobaldi. This study provided the first insight into the structure and function of the virome in highland lizards, contributing to the protection of threatened lizard species. Also, our research is of exemplary significance for the gut virome research of lizard species and other cold-blooded and highland-dwelling animals, prompting a better understanding of the interspecific differences and transmission of commensal viruses. IMPORTANCE The Phrynocephalus lizards inhabiting the Qinghai-Tibet Plateau (QTP) are considered to be the highest-altitude lizard species in the world, and they have been added to the IUCN list of threatened species. Living in the QTP with hypoxic, arid, natural conditions, the lizards presented a unique pattern of gut virome, which could provide both positive and negative effects, such as the enrichment of functional genes and the dissemination of antibiotic resistance genes (ARGs). This work provides the foundation for further research on the gut virome in these endangered lizard species and other cold-blooded and highland-dwelling animals, contributing to the maintenance of ecological balance on the plateau.

ABSTRACT Emerging coronaviruses (CoVs) can cause severe diseases in humans and animals, and, as of yet, none of the currently available broad-spectrum drugs or vaccines can effectively control these diseases. Host antiviral proteins play an important role in inhibiting viral proliferation. One of the isoforms of cytoplasmic poly(A)-binding protein (PABP), PABPC4, is an RNA-processing protein, which plays an important role in promoting gene expression by enhancing translation and mRNA stability. However, its function in viruses remains poorly understood. Here, we report that the host protein, PABPC4, could be regulated by transcription factor SP1 and broadly inhibits the replication of CoVs, covering four genera (Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus) of the Coronaviridae family by targeting the nucleocapsid (N) protein through the autophagosomes for degradation. PABPC4 recruited the E3 ubiquitin ligase MARCH8/MARCHF8 to the N protein for ubiquitination. Ubiquitinated N protein was recognized by the cargo receptor NDP52/CALCOCO2, which delivered it to the autolysosomes for degradation, resulting in impaired viral proliferation. In addition to regulating gene expression, these data demonstrate a novel antiviral function of PABPC4, which broadly suppresses CoVs by degrading the N protein via the selective autophagy pathway. This study will shed light on the development of broad anticoronaviral therapies. IMPORTANCE Emerging coronaviruses (CoVs) can cause severe diseases in humans and animals, but none of the currently available drugs or vaccines can effectively control these diseases. During viral infection, the host will activate the interferon (IFN) signaling pathways and host restriction factors in maintaining the innate antiviral responses and suppressing viral replication. This study demonstrated that the host protein, PABPC4, interacts with the nucleocapsid (N) proteins from eight CoVs covering four genera (Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus) of the Coronaviridae family. PABPC4 could be regulated by SP1 and broadly inhibits the replication of CoVs by targeting the nucleocapsid (N) protein through the autophagosomes for degradation. This study significantly increases our understanding of the novel host restriction factor PABPC4 against CoV replication and will help develop novel antiviral strategies.

Metagenomic analysis of mosquito-borne and mosquito-specific viruses is useful to understand the viral diversity and for the surveillance of pathogens of medical and veterinary importance. Yunnan province is located at the southwest of China and has rich abundance of mosquitoes. Arbovirus surveillance is not conducted regularly in this province particularly at animal farms, which have public health as well as veterinary importance. Here, we have analyzed 10 pools of mosquitoes belonging to Culex tritaeniorhyncus, Aedes aegypti, Anopheles sinensis, and Armigeres subalbatus species, collected from different animal farms located at Yunnan province of China by using metagenomic next-generation sequencing technique. The generated viral metagenomic data reveal that the viral community matched by the reads was highly diverse and varied in abundance among animal farms, which contained more than 19 viral taxonomic families, specific to vertebrates, invertebrates, fungi, plants, protozoa, and bacteria. Additionally, a large number of viral reads were related to viruses that are non-classified. The viral reads related to animal viruses included parvoviruses, anelloviruses, circoviruses, flaviviruses, rhabdoviruses, and seadornaviruses, which might be taken by mosquitoes from viremic animal hosts during blood feeding. Notably, the presence of viral reads matched with Japanese encephalitis virus, Getah virus, and porcine parvoviruses in mosquitoes collected from different geographic sites suggested a potential circulation of these viruses in their vertebrate hosts. Overall, this study provides a comprehensive knowledge of diverse viral populations present at animal farms of Yunnan province of China, which might be a potential source of diseases for humans and domestic animals. [ABSTRACT FROM AUTHOR]

Porcine epidemic diarrhea virus (PEDV) results in PED, which is an infectious intestinal disease with the representative features of diarrhea, vomiting, and dehydration. PEDV infects neonatal piglets, causing high mortality rates. Therefore, elucidating the interaction between the virus and host in preventing and controlling PEDV infection is of immense significance. We found a new antiviral function of the host protein, RNA-binding motif protein 14 (RBM14), which can inhibit PEDV replication via the activation of autophagy and interferon (IFN) signal pathways. We found that RBM14 can recruit cargo receptor p62 to degrade PEDV nucleocapsid (N) protein through the RBM14-p62-autophagosome pathway. Furthermore, RBM14 can also improve the antiviral ability of the hosts through interacting with mitochondrial antiviral signaling protein to induce IFN expression. These results highlight the novel mechanism underlying RBM14-induced viral restriction. This mechanism leads to the degradation of viral N protein via the autophagy pathway and upregulates IFN for inhibiting PEDV replication; thus, offering new ways for preventing and controlling PED. [ABSTRACT FROM AUTHOR]

In recent years, porcine deltacoronavirus (PDCoV) has become a new intestinal coronavirus in pigs, rapidly spreading across multiple countries and causing significant financial losses in the global pig industry. Currently, no effective commercial vaccine is available to prevent this virus' spread. Thus, it becomes crucial to investigate the interaction between the virus and its host to acquire valuable insights into the underlying mechanisms of viral replication and develop innovative strategies for preventing and controlling PDCoV. This study specifically focuses on exploring the regulatory effects of PGAM5, a mitochondrial protein, during viral proliferation. Our findings suggest that PDCoV infection hinders the expression of PGAM5 in LLC-PK1 cells. Additionally, it was also found that PGAM5 facilitates the degradation of the PDCoV N protein via the interaction with it, thereby inhibiting viral proliferation. Notably, the degradation of the PDCoV N protein by PGAM5 is mediated through its interaction with the cargo receptor P62 and the E3 ubiquitination ligase STUB1 during the protein degradation process. Furthermore, our results demonstrate that PGAM5 enhances the phosphorylation of IRF7, resulting in increased expression of type I interferon through its interaction with MyD88 and TRAF3, ultimately inhibiting PDCoV replication. Collectively, these findings elucidate the antiviral mechanism of PGAM5, which involves the degradation of the PDCoV N protein and activation of type I interferon to counteract viral replication. The obtained results emphasize the potential of PGAM5 as the novel target for preventing and treating PDCoV. [ABSTRACT FROM AUTHOR]

Porcine epidemic diarrhea virus (PEDV) causes severe morbidity and mortality among newborn piglets. It significantly threatens the porcine industry in China and around the globe. To accelerate the developmental pace of drugs or vaccines against PEDV, a deeper understanding of the interaction between viral proteins and host factors is crucial. The RNAbinding protein, polypyrimidine tract–binding protein 1 (PTBP1), is crucial for controlling RNA metabolism and biological processes. The present work focused on exploring the effect of PTBP1 on PEDV replication. PTBP1 was upregulated during PEDV infection. The PEDV nucleocapsid (N) protein was degraded through the autophagic and proteasomal degradation pathways. Moreover, PTBP1 recruits MARCH8 (an E3 ubiquitin ligase) and NDP52 (a cargo receptor) for N protein catalysis and degradation through selective autophagy. Furthermore, PTBP1 induces the host innate antiviral response via upregulating the expression of MyD88, which then regulates TNF receptor– associated factor 3/ TNF receptor–associated factor 6 expression and induces the phosphorylation of TBK1 and IFN regulatory factor 3. These processes activate the type I IFN signaling pathway to antagonize PEDV replication. Collectively, this work illustrates a new mechanism related to PTBP1-induced viral restriction, where PTBP1 degrades the viral N protein and induces type I IFN production to suppress PEDV replication [ABSTRACT FROM AUTHOR]

Porcine epidemic diarrhea (PED) indicates the disease of the acute and highly contagious intestinal infection due to porcine epidemic diarrhea virus (PEDV), with the characteristics of watery diarrhea, vomiting, and dehydration. One of the reasons for diarrhea and death of piglets is PEDV, which leads to 100% mortality in neonatal piglets. Therefore, it is necessary to explore the interaction between virus and host to prevent and control PEDV. This study indicated that the host protein, pre-mRNA processing factor 19 (PRPF19), could be controlled by the signal transducer as well as activator of transcription 1 (STAT1). Thus, PEDV replication could be hindered through selective autophagy. Moreover, PRPF19 was found to recruit the E3 ubiquitin ligase MARCH8 to the N protein for ubiquitination. For the purpose of degradation, the ubiquitin N protein is acknowledged by the cargo receptor NDP52 and transported to autolysosomes, thus inhibiting virus proliferation. To conclude, a unique antiviral mechanism of PRPF19-mediated virus restriction was shown. Moreover, a view of the innate immune response and protein degradation against PEDV replication was provided in this study. IMPORTANCE The highly virulent porcine epidemic diarrhea virus (PEDV) emerged in 2010, and causes high mortality rates in newborn pigs. There are no effective and safe vaccines against the highly virulent PEDV. This virus has caused devastating economic losses in the pork industry worldwide. Studying the relationship between virus and host antiviral factors is important to develop the new antiviral strategies. This study identified the pre-mRNA processing factor 19 (PRPF19) as a novel antiviral protein in PEDV replication and revealed its viral restriction mechanisms for the first time. PRPF19 recruited the E3 ubiquitin ligase MARCH8 to the PEDV N protein for ubiquitination, and the ubiquitin N protein was acknowledged by the cargo receptor NDP52 and transported to autolysosomes for degradation. Our findings provide new insights in host antiviral factors PRPF19 that regulate the selective autophagy protein degradation pathway to inhibit PEDV replication. [ABSTRACT FROM AUTHOR]