DRodVir:A resource for exploring the virome diversity in rodents

Emerging zoonotic diseases have received tremendous interests in recent years,as they pose a significant threat to human health,animal welfare,and economic stability.A high proportion of zoonoses originate from wildlife reservoirs.Rodents are the most numerous,widespread,and diverse group of mammals on the earth and are reservoirs for many zoonotic viruses responsible for significant morbidity and mortality.A better understanding of virome diversity in rodents would be of importance for researchers and professionals in the field.Therefore,we developed the DRodVir database(http://www.mgc.ac.cn/DRodVir/),a comprehensive,up-to-date,and well-curated repository of rodent-associated animal viruses.The database currently covers 7690 sequences from 5491 rodent-associated mammal viruses of 26 viral families detected from 194 rodent species in 93 countries worldwide.In addition to virus sequences,the database provides detailed information on related samples and host rodents,as well as a set of online analytical tools for text query,BLAST search and phylogenetic reconstruction.The DRodVir database will help virologists better understand the virome diversity of rodents.Moreover,it will be a valuable tool for epidemiologists and zoologists for easy monitoring and tracking of the current and future zoonotic diseases.As a data application example,we further compared the current status of rodent-associated viruses with bat-associated viruses to highlight the necessity for including additional host species and geographic regions in future investigations,which will help us achieve a better understanding of the virome diversities in the two major reservoirs of emerging zoonotic infectious diseases.     

Viral infections at the animal–human interface—Learning lessons from the SARS-CoV-2 pandemic

This Lilliput explores the current epidemiological and virological arguments for a zoonotic origin of the COVID-19 pandemic. While the role of bats, pangolins and racoon dogs as viral reservoirs has not yet been proven, a spill-over of a coronavirus infection from animals into humans at the Huanan food market in Wuhan has a much greater plausibility than alternative hypotheses such as a laboratory virus escape, deliberate genetic engineering or introduction by cold chain food products. This Lilliput highlights the dynamic nature of the animal-human interface for viral cross-infections from humans into feral white tail deer or farmed minks (reverse zoonosis). Surveillance of viral infections at the animal-human interface is an urgent task since live animal markets are not the only risks for future viral spill-overs. Climate change will induce animal migration which leads to viral exchanges between animal species that have not met in the past. Environmental change and deforestation will also increase contact between animals and humans. Developing an early warning system for emerging viral infections becomes thus a societal necessity not only for human but also for animal and environmental health (One Health concept). Microbiologists have developed tools ranging from virome analysis in key suspects such as viral reservoirs (bats, wild game animals, bushmeat) and in humans exposed to wild animals, to wastewater analysis to detect known and unknown viruses circulating in the human population and sentinel studies in animal-exposed patients with fever. Criteria need to be developed to assess the virulence and transmissibility of zoonotic viruses. An early virus warning system is costly and will need political lobbying. The accelerating number of viral infections with pandemic potential over the last decades should provide the public pressure to extend pandemic preparedness for the inclusion of early viral alert systems.     

Current trends in large‐scale viral surveillance methods in mosquitoes

Vector‐borne and zoonotic infectious diseases are serious public health concerns that affect approximately half of the world's population. In particular, arthropod‐borne viruses (arboviruses) have contributed to more mortality and morbidity worldwide with the emergence of dengue, chikungunya, yellow fever, and Zika virus diseases. The infections have scaled up due to urbanization, globalization, and international mobility. Traditionally, the spread of mosquito‐borne viral diseases to humans was considered a low health priority concern. However, their categorization as emerging infectious diseases and public health emergencies of international concern has heightened the attention given by the government, academia, research, and industry for the development of timely, cost‐efficient, and sustainable solutions. The urgency has increased in the wake of global climate change. The focus on effective interventions includes epidemiological monitoring, vector control measures, molecular diagnostics, vaccines, and environmental determinants. In this review, we discuss the etiology and predisposition of mosquito‐borne viruses that are detrimental to public health and economically damaging when disseminated as epidemics. We focus on the large‐scale virus surveillance methods with special reference to innovations and interventions in molecular detection science and technologies that include viral nucleic acid isolation, polymerase chain reaction (PCR)‐based diagnostics, and high‐throughput sequencing technologies. In addition, we discuss the development of a viral RNA extraction and PCR‐based diagnostic kit (Invirustech) that can extract viral RNA from mosquitoes with verified applications in PCR‐based molecular diagnostics of Pan‐flavivirus.     

Deciphering the bat virome catalog to better understand the ecological diversity of bat viruses and the bat origin of emerging infectious diseases

Studies have demonstrated that ~60%–80% of emerging infectious diseases (EIDs) in humans originated from wild life. Bats are natural reservoirs of a large variety of viruses, including many important zoonotic viruses that cause severe diseases in humans and domestic animals. However, the understanding of the viral population and the ecological diversity residing in bat populations is unclear, which complicates the determination of the origins of certain EIDs. Here, using bats as a typical wildlife reservoir model, virome analysis was conducted based on pharyngeal and anal swab samples of 4440 bat individuals of 40 major bat species throughout China. The purpose of this study was to survey the ecological and biological diversities of viruses residing in these bat species, to investigate the presence of potential bat-borne zoonotic viruses and to evaluate the impacts of these viruses on public health. The data obtained in this study revealed an overview of the viral community present in these bat samples. Many novel bat viruses were reported for the first time and some bat viruses closely related to known human or animal pathogens were identified. This genetic evidence provides new clues in the search for the origin or evolution pattern of certain viruses, such as coronaviruses and noroviruses. These data offer meaningful ecological information for predicting and tracing wildlife-originated EIDs.     

Inhibition of enveloped virus infection of cultured cells by valproic acid

Valproic acid (VPA) is a short-chain fatty acid commonly used for treatment of neurological disorders. As VPA can interfere with cellular lipid metabolism, its effect on the infection of cultured cells by viruses of seven viral families relevant to human and animal health, including eight enveloped and four nonenveloped viruses, was analyzed. VPA drastically inhibited multiplication of all the enveloped viruses tested, including the zoonotic lymphocytic choriomeningitis virus and West Nile virus (WNV), while it did not affect infection by the nonenveloped viruses assayed. VPA reduced vesicular stomatitis virus infection yield without causing a major blockage of either viral RNA or protein synthesis. In contrast, VPA drastically abolished WNV RNA and protein synthesis, indicating that this drug can interfere the viral cycle at different steps of enveloped virus infection. Thus, VPA can contribute to an understanding of the crucial steps of viral maturation and to the development of future strategies against infections associated with enveloped viruses.     

The fecal virome of pigs on a high-density farm

Swine are an important source of proteins worldwide but are subject to frequent viral outbreaks and numerous infections capable of infecting humans. Modern farming conditions may also increase viral transmission and potential zoonotic spread. We describe here the metagenomics-derived virome in the feces of 24 healthy and 12 diarrheic piglets on a high-density farm. An average of 4.2 different mammalian viruses were shed by healthy piglets, reflecting a high level of asymptomatic infections. Diarrheic pigs shed an average of 5.4 different mammalian viruses. Ninety-nine percent of the viral sequences were related to the RNA virus families Picornaviridae, Astroviridae, Coronaviridae, and Caliciviridae, while 1% were related to the small DNA virus families Circoviridae, and Parvoviridae. Porcine RNA viruses identified, in order of decreasing number of sequence reads, consisted of kobuviruses, astroviruses, enteroviruses, sapoviruses, sapeloviruses, coronaviruses, bocaviruses, and teschoviruses. The near-full genomes of multiple novel species of porcine astroviruses and bocaviruses were generated and phylogenetically analyzed. Multiple small circular DNA genomes encoding replicase proteins plus two highly divergent members of the Picornavirales order were also characterized. The possible origin of these viral genomes from pig-infecting protozoans and nematodes, based on closest sequence similarities, is discussed. In summary, an unbiased survey of viruses in the feces of intensely farmed animals revealed frequent coinfections with a highly diverse set of viruses providing favorable conditions for viral recombination. Viral surveys of animals can readily document the circulation of known and new viruses, facilitating the detection of emerging viruses and prospective evaluation of their pathogenic and zoonotic potentials.     

Sequence-independent characterization of viruses based on the pattern of viral small RNAs produced by the host

Virus surveillance in vector insects is potentially of great benefit to public health. Large-scale sequencing of small and long RNAs has previously been used to detect viruses, but without any formal comparison of different strategies. Furthermore, the identification of viral sequences largely depends on similarity searches against reference databases. Here, we developed a sequence-independent strategy based on virus-derived small RNAs produced by the host response, such as the RNA interference pathway. In insects, we compared sequences of small and long RNAs, demonstrating that viral sequences are enriched in the small RNA fraction. We also noted that the small RNA size profile is a unique signature for each virus and can be used to identify novel viral sequences without known relatives in reference databases. Using this strategy, we characterized six novel viruses in the viromes of laboratory fruit flies and wild populations of two insect vectors: mosquitoes and sandflies. We also show that the small RNA profile could be used to infer viral tropism for ovaries among other aspects of virus biology. Additionally, our results suggest that virus detection utilizing small RNAs can also be applied to vertebrates, although not as efficiently as to plants and insects.     

Tracing the future of epidemics: Coincident niche distribution of host animals and disease incidence revealed climate-correlated risk shifts of main zoonotic diseases in China

Climate has critical roles in the origin, pathogenesis and transmission of infectious zoonotic diseases. However, large-scale epidemiologic trend and specific response pattern of zoonotic diseases under future climate scenarios are poorly understood. Here, we projected the distribution shifts of transmission risks of main zoonotic diseases under climate change in China. First, we shaped the global habitat distribution of main host animals for three representative zoonotic diseases (2, 6, and 12 hosts for dengue, hemorrhagic fever, and plague, respectively) with 253,049 occurrence records using maximum entropy (Maxent) modeling. Meanwhile, we predicted the risk distribution of the above three diseases with 197,098 disease incidence records from 2004 to 2017 in China using an integrated Maxent modeling approach. The comparative analysis showed that there exist highly coincident niche distributions between habitat distribution of hosts and risk distribution of diseases, indicating that the integrated Maxent modeling is accurate and effective for predicting the potential risk of zoonotic diseases. On this basis, we further projected the current and future transmission risks of 11 main zoonotic diseases under four representative concentration pathways (RCPs) (RCP2.6, RCP4.5, RCP6.0, and RCP8.5) in 2050 and 2070 in China using the above integrated Maxent modeling with 1,001,416 disease incidence records. We found that Central China, Southeast China, and South China are concentrated regions with high transmission risks for main zoonotic diseases. More specifically, zoonotic diseases had diverse shift patterns of transmission risks including increase, decrease, and unstable. Further correlation analysis indicated that these patterns of shifts were highly correlated with global warming and precipitation increase. Our results revealed how specific zoonotic diseases respond in a changing climate, thereby calling for effective administration and prevention strategies. Furthermore, these results will shed light on guiding future epidemiologic prediction of emerging infectious diseases under global climate change.     

贵州省四种蝙蝠携带病毒组

翼手目(Chiroptera)动物已被确认是人畜共患病毒的重要自然宿主。贵州省翼手目物种多样性资源丰富,包括了2亚目7科19属65种,但在其携带病毒方面的研究仍然不全面。本文基于病毒宏基因组学和s RNA病毒检测,对贵州省广泛分布的大蹄蝠(Hipposideriderosarmiger)、三叶蹄蝠(Aselliscus wheeleri)、贵州菊头蝠(Rhinolophus rex)和皮氏菊头蝠(R. pearsoni)携带的病毒进行注释及鉴定。通过分析得到所携带病毒的种类;并比较了贵州省与云南省和广西省3个地区翼手目携带病毒在种类上的差异。结果显示,在4种蝙蝠中检测出脊椎动物病毒、昆虫病毒、植物病毒、细菌病毒4大类,共计53科111属170余种病毒,其中具有公共卫生学意义病毒9科10属46种,如:人疱疹病毒1型病毒(Human herpesvirus 1)、戊型肝炎病毒(Hepatitis E virus)、人乳头瘤病毒16型(Human papillomavirustype16)等相关的病毒。贵州省与云南省和广西省3个地区的蝙蝠所携带病毒种类比较发现,只有腺病毒科(Adenovir...     

Distinct Host Tropism Protein Signatures to Identify Possible Zoonotic Influenza A Viruses

Zoonotic influenza A viruses constantly pose a health threat to humans as novel strains occasionally emerge from the avian population to cause human infections. Many past epidemic as well as pandemic strains have originated from avian species. While most viruses are restricted to their primary hosts, zoonotic strains can sometimes arise from mutations or reassortment, leading them to acquire the capability to escape host species barrier and successfully infect a new host. Phylogenetic analyses and genetic markers are useful in tracing the origins of zoonotic infections, but there are still no effective means to identify high risk strains prior to an outbreak. Here we show that distinct host tropism protein signatures can be used to identify possible zoonotic strains in avian species which have the potential to cause human infections. We have discovered that influenza A viruses can now be classified into avian, human, or zoonotic strains based on their host tropism protein signatures. Analysis of all influenza A viruses with complete proteome using the host tropism prediction system, based on machine learning classifications of avian and human viral proteins has uncovered distinct signatures of zoonotic strains as mosaics of avian and human viral proteins. This is in contrast with typical avian or human strains where they show mostly avian or human viral proteins in their signatures respectively. Moreover, we have found that zoonotic strains from the same influenza outbreaks carry similar host tropism protein signatures characteristic of a common ancestry. Our results demonstrate that the distinct host tropism protein signature in zoonotic strains may prove useful in influenza surveillance to rapidly identify potential high risk strains circulating in avian species, which may grant us the foresight in anticipating an impending influenza outbreak.     

Targeting Membrane-Bound Viral RNA Synthesis Reveals Potent Inhibition of Diverse Coronaviruses Including the Middle East Respiratory Syndrome Virus

Coronaviruses raise serious concerns as emerging zoonotic viruses without specific antiviral drugs available. Here we screened a collection of 16671 diverse compounds for anti-human coronavirus 229E activity and identified an inhibitor, designated K22, that specifically targets membrane-bound coronaviral RNA synthesis. K22 exerts most potent antiviral activity after virus entry during an early step of the viral life cycle. Specifically, the formation of double membrane vesicles (DMVs), a hallmark of coronavirus replication, was greatly impaired upon K22 treatment accompanied by near-complete inhibition of viral RNA synthesis. K22-resistant viruses contained substitutions in non-structural protein 6 (nsp6), a membrane-spanning integral component of the viral replication complex implicated in DMV formation, corroborating that K22 targets membrane bound viral RNA synthesis. Besides K22 resistance, the nsp6 mutants induced a reduced number of DMVs, displayed decreased specific infectivity, while RNA synthesis was not affected. Importantly, K22 inhibits a broad range of coronaviruses, including Middle East respiratory syndrome coronavirus (MERS–CoV), and efficient inhibition was achieved in primary human epithelia cultures representing the entry port of human coronavirus infection. Collectively, this study proposes an evolutionary conserved step in the life cycle of positive-stranded RNA viruses, the recruitment of cellular membranes for viral replication, as vulnerable and, most importantly, druggable target for antiviral intervention. We expect this mode of action to serve as a paradigm for the development of potent antiviral drugs to combat many animal and human virus infections.     

Tick‐borne viruses: Current trends in large‐scale viral surveillance

Ticks are ectoparasites that transmit pathogens, such as tick‐borne viruses, to their hosts. Tick‐borne viruses are diverse: they can be categorized into two orders, nine families, and at least 12 genera. Almost 25% of these viruses are infectious to humans and some are a serious threat to public health. The global rise in tick‐borne virus diseases has been linked to climate change which has reduced tick mortality in the winter and extended their active period. The spread of tick‐borne viral diseases to humans has received significant interest due to the increased threat to human life; epidemiological monitoring of tick‐borne viruses using molecular, immunological, and environmental methods is now a priority. Nevertheless, many tick‐borne diseases remain undiagnosed, which poses a challenge to public administration and health care officials. This review discusses three major tick‐borne RNA viruses that cause serious infection in humans: severe fever with thrombocytopenia syndrome (SFTS) virus, tick‐borne encephalitis (TBE), and Crimean–Congo hemorrhagic fever (CCHF) virus. Specifically, we discuss the epidemiological monitoring, vector control measures, molecular diagnostics, vaccines, and environmental determinants related to these viruses. Furthermore, we review the current surveillance of these tick‐borne viruses with a specific focus on diagnostic approaches that employ molecular interventions such as viral nucleic acid isolation, PCR‐based diagnostics, and high‐throughput sequencing technologies.     

A Preliminary Study of Viral Metagenomics of French Bat Species in Contact with Humans: Identification of New Mammalian Viruses

The prediction of viral zoonosis epidemics has become a major public health issue. A profound understanding of the viral population in key animal species acting as reservoirs represents an important step towards this goal. Bats harbor diverse viruses, some of which are of particular interest because they cause severe human diseases. However, little is known about the diversity of the global population of viruses found in bats (virome). We determined the viral diversity of five different French insectivorous bat species (nine specimens in total) in close contact with humans. Sequence-independent amplification, high-throughput sequencing with Illumina technology and a dedicated bioinformatics analysis pipeline were used on pooled tissues (brain, liver and lungs). Comparisons of the sequences of contigs and unassembled reads provided a global taxonomic distribution of virus-related sequences for each sample, highlighting differences both within and between bat species. Many viral families were present in these viromes, including viruses known to infect bacteria, plants/fungi, insects or vertebrates, the most relevant being those infecting mammals (Retroviridae, Herpesviridae, Bunyaviridae, Poxviridae, Flaviviridae, Reoviridae, Bornaviridae, Picobirnaviridae). In particular, we detected several new mammalian viruses, including rotaviruses, gammaretroviruses, bornaviruses and bunyaviruses with the identification of the first bat nairovirus. These observations demonstrate that bats naturally harbor viruses from many different families, most of which infect mammals. They may therefore constitute a major reservoir of viral diversity that should be analyzed carefully, to determine the role played by bats in the spread of zoonotic viral infections.     

A comparison of bats and rodents as reservoirs of zoonotic viruses: are bats special?

Bats are the natural reservoirs of a number of high-impact viral zoonoses. We present a quantitative analysis to address the hypothesis that bats are unique in their propensity to host zoonotic viruses based on a comparison with rodents, another important host order. We found that bats indeed host more zoonotic viruses per species than rodents, and we identified life-history and ecological factors that promote zoonotic viral richness. More zoonotic viruses are hosted by species whose distributions overlap with a greater number of other species in the same taxonomic order (sympatry). Specifically in bats, there was evidence for increased zoonotic viral richness in species with smaller litters (one young), greater longevity and more litters per year. Furthermore, our results point to a new hypothesis to explain in part why bats host more zoonotic viruses per species: the stronger effect of sympatry in bats and more viruses shared between bat species suggests that interspecific transmission is more prevalent among bats than among rodents. Although bats host more zoonotic viruses per species, the total number of zoonotic viruses identified in bats (61) was lower than in rodents (68), a result of there being approximately twice the number of rodent species as bat species. Therefore, rodents should still be a serious concern as reservoirs of emerging viruses. These findings shed light on disease emergence and perpetuation mechanisms and may help lead to a predictive framework for identifying future emerging infectious virus reservoirs.     

CD8 T cell responses to viral infections in sequence

Our current understanding of virus-specific T cell responses has been shaped by model systems with mice, where naive animals are infected with a single viral pathogen. Paradigms derived from such models, however, may not always be applicable to a natural setting, where a host is exposed to numerous pathogens over its lifetime. Accumulating data in animal models and with some human diseases indicate that a host's prior history of infections can impact the specificity of future CD8 T cell responses, even to unrelated viruses. This can have both beneficial and detrimental consequences for the host, including altered clearance of virus, distinct forms of immunopathology, and substantial changes in the pool of memory T cells. Here we will describe the characteristics of CD8 T cells and the dynamics of their response to heterologous viral infections in sequence.     

RNA‐Directed rna polymerases of plants

The report in 1971 by Comuet and Astier‐Manifacier that Chinese cabbage contains an active RNA‐dependent RNA polymerase has been extended to all plants studied. This has met with much opposition because the central dogma of molecular biology requires no replication mechanism for RNA. Only upon RNA virus infection are such enzymes needed, and it was generally believed that these were always and only virus‐coded. The purification and characterization of several of these plant viruses will be reviewed, with particular reference to the fact that while their amount in plant tissue is variably increased by various RNA virus infections their nature is unaffected by the viral genome and is strictly host‐specific. It will be noted, however, that in a specific instance viral infection has been shown to affect an important property of the enzyme. Also, it has become evident that certain plant viruses resemble animal picorna viruses (e.g., polio virus) and that these viruses carry an RNA polymerase gene. The same may be true, but has not been proven, for a small group of plant viruses that shows resemblances to the prokaryotic RNA phages in which a viral gene product together with host proteins form the RNA polymerase. An important question that remains to be solved in future work is the role of RNA polymerases in normal plant cell biology. Also, the mechanism by which viral infection causes the enzyme to become largely membrane or organelle bound and possibly conformationally changed in the process remains to be elucidated.     

Enteric Viruses of Humans and Animals in Aquatic Environments: Health Risks, Detection, and Potential Water Quality Assessment Tools

Waterborne enteric viruses threaten both human and animal health. These pathogens are host specific and cause a wide range of diseases and symptoms in humans or other animals. While considerable research has documented the risk of enteric viruses to human health from contact with contaminated water, the current bacterial indicator-based methods for evaluation of water quality are often ineffectual proxies for pathogenic viruses. Additionally, relatively little work has specifically investigated the risk of waterborne viruses to animal health, and this risk currently is not addressed by routine water quality assessments. Nonetheless, because of their host specificity, enteric viruses can fulfill a unique role both for assessing health risks and as measures of contamination source in a watershed, yet the use of animal, as well as human, host-specific viruses in determining sources of fecal pollution has received little attention. With improved molecular detection assays, viruses from key host groups can be targeted directly using PCR amplification or hybridization with a high level of sensitivity and specificity. A multispecies viral analysis would provide needed information for controlling pollution by source, determining human health risks based on assessments of human virus loading and exposure, and determining potential risks to production animal health and could indicate the potential for the presence of other zoonotic pathogens. While there is a need to better understand the prevalence and environmental distribution of nonhuman enteric viruses, the development of improved methods for specific and sensitive detection will facilitate the use of these microbes for library-independent source tracking and water quality assessment tools.     

RNA 沉默的病毒抑制子

RNA 沉默是一种在真核生物体内普遍保守的、通过核酸序列特异性的相互作用来抑制基因表达的调控机制 . RNA 沉默的一种重要生物学效应是防御病毒的侵染,而针对寄主的这种防御机制,许多植物病毒已演化通过编码 RNA 沉默的抑制子来克服这种防御反应 . 目前,已从植物、动物和人类病毒中鉴定了 20 多种 RNA 沉默的抑制子,围绕抑制子的鉴定和作用机理研究已成为病毒学研究的一个热点 . 对 RNA 沉默抑制子的发现、鉴定方法、作用机理及与病毒病症状形成的关系、动物病毒的沉默抑制子等方面的最新进展做了综述,并对沉默抑制子的应用和存在的问题进行了讨论 .     

Paramyxovirus assembly and budding: Building particles that transmit infections

The paramyxoviruses define a diverse group of enveloped RNA viruses that includes a number of important human and animal pathogens. Examples include human respiratory syncytial virus and the human parainfluenza viruses, which cause respiratory illnesses in young children and the elderly; measles and mumps viruses, which have caused recent resurgences of disease in developed countries; the zoonotic Hendra and Nipah viruses, which have caused several outbreaks of fatal disease in Australia and Asia; and Newcastle disease virus, which infects chickens and other avian species. Like other enveloped viruses, paramyxoviruses form particles that assemble and bud from cellular membranes, allowing the transmission of infections to new cells and hosts. Here, we review recent advances that have improved our understanding of events involved in paramyxovirus particle formation. Contributions of viral matrix proteins, glycoproteins, nucleocapsid proteins, and accessory proteins to particle formation are discussed, as well as the importance of host factor recruitment for efficient virus budding. Trafficking of viral structural components within infected cells is described, together with mechanisms that allow for the selection of specific sites on cellular membranes for the coalescence of viral proteins in preparation of bud formation and virion release.