Cross-species Transmission Research Articles

Pandemic-Proofing: Intercepting Zoonotic Spillover Events

Zoonotic spillover events pose a significant and growing threat to global health. By focusing on preventing these cross-species transmissions, we can significantly mitigate pandemic risks. This review aims to analyze the mechanisms of zoonotic spillover events, identify key risk factors, and propose evidence-based prevention strategies to reduce future pandemic threats. Through a comprehensive literature review and analysis of major databases including PubMed, Web of Science, and Scopus from 1960–2024, we examined documented spillover events, their outcomes, and intervention strategies. This article emphasizes that targeting the root cause—the spillover event itself—is key to averting future pandemics. By analyzing historical and contemporary outbreaks, we extract crucial insights into the dynamics of zoonotic transmission. Factors underlying these events include increased human–animal contact due to habitat encroachment, agricultural intensification, and wildlife trade. Climate change, global travel, and inadequate healthcare infrastructure exacerbate risks. The diversity of potential viral reservoirs and rapid viral evolution present major challenges for prediction and prevention. Solutions include enhancing surveillance of wildlife populations, improving biosecurity measures, investing in diagnostic capabilities, and promoting sustainable wildlife management. A “One Health” approach integrating human, animal, and environmental health is crucial. Predictive modelling, international cooperation, and public education are key strategies. Developing pre-exposure prophylactics and post-exposure treatments is essential for mitigating outbreaks. While obstacles remain, advances in genomics and ecological modelling offer hope. A proactive, comprehensive approach addressing the root causes of spillover events is vital for safeguarding global health against future pandemics.

Mamastrovirus spike protein: Sequence and structural characterization as a basis for understanding cross-species transmission

Astroviruses (AstVs) are notable for their propensity for cross-species transmission; however, the molecular determinants underlying this phenomenon remain poorly understood. The spike protein, which is responsible for host cell entry and is a major antigenic determinant, is hypothesized to play a pivotal role. In this study, we observed high sequence variability in the spike region of AstV. Structural analyses have revealed variability, arising from diverse evolutionary relationships, among AstVs of the same host origin. AstV spike proteins can be categorized into six groups, each of which encompasses AstVs from diverse hosts that exhibit high degrees of structural similarity. These six groups correspond to branches observed in the phylogenetic tree. Notably, the spike surface-exposed loops emerged as focal hotspots for B-cell epitopes across groups, with sequence variability that may contribute to immune evasion upon host switching. Differences in the spike structures of AstVs infecting the same host raise the possibility of distinct tissue tropisms and corresponding clinical manifestations. Collectively, our findings provide insights into the roles of spike protein similarities and immune epitope diversity in driving AstV cross-species transmission. Understanding these molecular mechanisms is crucial to predicting and mitigating the emergence of novel AstV strains.

Antigenic switch potential of influenza D virus

The antigenic variability of Influenza D virus (IDV), a recently identified pathogen with significant implications for livestock and zoonotic diseases, presents unique challenges in virology, epidemiology, and public health. This review stands out by focusing explicitly on IDV's distinct antigenic shift and drift mechanisms, which are underexplored compared to other influenza viruses. Unlike previous studies that broadly address influenza evolution, this research emphasizes IDV’s specific molecular and ecological traits, particularly its hemagglutinin-esterase fusion (HEF) protein, which plays a critical role in antigenic reconfiguration. The study integrates genomic sequencing, structural bioinformatics, and epidemiological surveillance to deliver a comprehensive understanding of IDV's evolutionary potential and cross-species transmission risks. This review uniquely highlights IDV’s moderate propensity for antigenic switching, particularly in livestock reservoirs such as cattle and swine, which act as amplification hosts for viral dissemination. By rigorously mapping the virus’s antigenic architecture, this work provides novel insights into its adaptive mechanisms and evolutionary trajectory, offering practical implications for vaccine development, immune evasion strategies, and interspecies transmission control. The methodological foundation includes an exhaustive review of peer-reviewed literature, in silico simulations, and phylogenetic analyses, setting this study apart as a detailed exploration of IDV’s antigenic dynamics. Findings emphasize the challenges posed by IDV variability for sustainable vaccine development, necessitating regular updates to address ongoing antigenic shifts. This study significantly advances global efforts to understand and manage IDV evolution, underscoring the urgent need for enhanced surveillance in agricultural, veterinary, and public health systems. By doing so, it bridges critical knowledge gaps and informs future diagnostic, therapeutic, and preventive strategies tailored to mitigate zoonotic threats.

2024 Mpox outbreak: A rapidly evolving public health emergency of international concern

The declaration of a second Public Health Emergency of International Concern (PHEIC) for mpox in August 2024 underscores the urgent need for a comprehensive understanding of the evolving epidemiology [1] clinical manifestations, and zoonotic potential of this emerging threat [2]. This work delves into the intricate interplay between human and animal mpox infections, with a specific focus on the unique characteristics of various viral clades and their implications for individual and public health.There is a critical need to elucidate the factors driving multiple spillover events and the subsequent emergence of new clades better adapted to human-to-human transmission. We hypothesize that anthropogenic changes, including deforestation, urbanization, and climate change are facilitating increased human-to-animal contact, leading to more frequent zoonotic transmissions and viral adaptations. Our conceptual framework integrates One Health principles, evolutionary virology, and epidemiological modeling to investigate the demographic, clinical, and treatment differences among mpox clades in both humans and animals. We employ a mixed-methods approach, combining genomic analysis, clinical data review, and ecological surveys to construct a comprehensive picture of mpox's changing dynamics. The research questions explore the differences in epidemiological and clinical profiles among mpox clades and the factors that likely contribute to successful cross-species transmission and human adaptation.This manuscript introduces an updated Identify, Isolate, Inform (3I) Tool meticulously redesigned to significantly improve the early detection, containment, and reporting of mpox cases across diverse settings. By integrating clinical, virological, and ecological data, this work aims to lay the groundwork for enhanced risk assessment, targeted interventions, and global preparedness strategies in the face of this evolving zoonotic threat.

Zoonotic Potential of Chronic Wasting Disease after Adaptation in Intermediate Species.

Chronic wasting disease (CWD) is an emerging disease in Europe. We report an increase in interspecies transmission capacity and zoonotic potential of a moose CWD isolate from Europe after passage in an ovine prion protein-expressing host. Those results indicated some CWD prions could acquire enhanced zoonotic properties following adaptation in an intermediate species.

Transcriptome analysis reveals that PRV XJ delgE/gI/TK protects against intestinal damage in nose-dropping-infected mice by regulating ECM-ITGA/ITGB-P-FAK.

Pseudorabies virus (PRV) is an ideal model for mechanistic investigations into α-herpesvirus. The neurotropism and latent infection of PRV have been extensively studied. Apart from neurological symptoms, diarrhea caused by PRV infection is also an essential cause of mortality in newborn and weaned piglets. However, little research has been done on PRV invasion of the gut. To fill this gap, a nasal drip PRV-infection mouse model was developed, consisting of three groups: the challenged group (Group A), the immunization-challenged group (Group B), and a mock group (Group C). The results showed that immunization with PRV XJ delgE/gI/TK successfully prevented intestinal damage caused by PRV drop-nose infection. Subsequently, intestines were collected for transcriptional analysis. Differentially expressed genes analysis revealed that PRV XJ delgE/gI/TK was effective in reducing the organismal intestinal transcriptional activity caused by PRV. The Group A vs Group C and Group A vs Group B had similar Kyoto Encyclopedia of Genes and Genomes (KEGG)-enriched signaling pathways and the differentially expressed genes were primarily enriched in pathways, such as cell adhesion molecules, focal adhesion kinase, and actin cytoskeleton regulation. Notably, transcriptome analysis indicated that genes associated with the focal adhesion kinase (FAK) signaling pathway (ECM-ITGA/ITGB-p-FAK) were significantly more highly expressed in Group A than in Group B and Group C. The results of quantitative real-time PCR (RT-qPCR) and western blotting were consistent with KEGG analysis. Therefore, we hypothesized that PRV promotes self-infection through activation of the ECM-ITGA/ITGB-p-FAK signaling pathway and that PRV XJ delgE/gI/TK immunization could attenuate the intestinal damage caused by PRV by inhibiting the activation of this pathway.IMPORTANCEPseudorabies virus (PRV) poses a significant threat to the swine industry and public health due to its ability to infect multiple species, including humans, leading to substantial economic losses and potential health risks. This study addresses a critical gap in understanding the impact of PRV infection on the gut, which has been less explored compared to its neurological effects. By developing a drip-nose PRV-infection mouse model, the research indicated that PRV might promote self-infection through activation of the ECM-ITGA/ITGB-p-FAK signaling pathway, and PRV XJ delgE/gI/TK immunization effectively prevents intestinal damage by significantly reducing the expression of genes in the ECM-ITGA/ITGB-p-FAK signaling pathway. The research has important implications for the swine industry and public health by contributing to the development of better vaccines and treatments, ultimately helping to control PRV and prevent its cross-species transmission.

Genetic characterization and clonal analysis of carbapenemase-producing Escherichia coli and Klebsiella pneumoniae from canine and human origins

IntroductionCarbapenem-resistant Enterobacterales (CRE), particularly carbapenemase-producing Escherichia coli and Klebsiella pneumoniae, pose a significant global health challenge due to their resistance to last-resort antibiotics. This study investigates the genetic characteristics and clonal relationships of CRE isolated from canine and human clinical samples in Bangkok to understand potential interspecies transmission.MethodsFifty-two CRE isolates were collected from 477 clinical samples from dogs and humans at Chulalongkorn University between 2017–2021. Bacterial species were identified using MALDI-TOF, and antimicrobial resistance was confirmed through broth microdilution testing. Genetic analyses included plasmid replicon typing, multilocus sequence typing (MLST), whole genome sequencing (WGS), and pulsed-field gel electrophoresis (PFGE) to assess resistance genes and clonal relatedness.ResultsCRE isolates from both species exhibited genetic variability with high ARG counts, particularly in human isolates. MLST identified ST410 in most E. coli isolates from both dogs and humans, and IncFIA/IncFIB plasmids were predominant among blaNDM-positive isolates. PFGE patterns and SNP analysis showed no clonal relationship between canine and human isolates, suggesting independent acquisition pathways for CRE in the two hosts.DiscussionThe study highlights the absence of direct clonal transmission between canine and human isolates but reveals overlapping sequence types and plasmid types. The findings underscore the potential for interspecies transmission under certain conditions, emphasizing the importance of a One Health approach for monitoring CRE in both human and animal populations.

Studies on the resistance of three pathogens isolated from wild Charybdis japonica and their pathogenicity in Portunus trituberculatus

The coagulation property of hemolymph is one of the characteristic indicators of the immune function of crustaceans. This article focuses on the abnormal phenomenon of wild Charybdis japonica, where the hemolymph cannot coagulate in the Qinhuangdao Sea area. The pathogens were isolated and purified, and three dominant strains, N1, N2, and Q1, were obtained. These strains were identified as Vibrio natriegens, V. fortis, and Metschnikowia bicuspidata through morphological observation, physiological and biochemical experiments, and 16S rDNA or ITS sequence analysis. Subsequently, drug sensitivity and probiotic antagonism analyses were performed. Considering the potential for cross-species transmission of crustacean pathogens, the isolated pathogens may bring potential hazards to Portunus trituberculus, an important aquaculture economic species in China. Therefore, artificial infection and histopathological analysis were conducted on P. trituberculatus. The results of drug sensitivity and antagonism assays revealed that stain V. natriegens exhibited susceptibilities towards antibiotics such as streptomycin and norfloxacin, but 10 probiotics had no antagonistic effect on it; strain V. fortis exhibited susceptibilities to antibiotics such as tetracycline and chloramphenicol, moreover, strain V. fortis showed inhibitory effects on Bacillus velezensis and B. amyloliquefaciens. Strain M. bicuspidata exhibited drug susceptibility towards polymyxin B and showed inhibitory effects on B. toyonensis, B. velezensis, and B. amyloliquefaciens. The results of artificial infection tests using V. natriegens, V. fortis, and M. bicuspidata in P. trituberculatus showed cumulative mortality rates of 100%, 75%, and 35%, respectively, after 120 hours of infection. The hemolymph of the deceased P. trituberculatus following injection with strain V. natriegens or V. fortis exhibited a light blue and did not coagulate normally. Conversely, the hemolymph of the deceased crabs following injection with strain M. bicuspidata appeared milky white and normal coagulation. Histopathology examination demonstrated that strains V. natriegens, V. fortis, and M. bicuspidata can all induce lesions in several tissues. This study is the first to isolate V. natriegens and V. fortis from crustaceans, and the infection tests on the P. trituberculatus can replicate the symptoms, such as hemolymph noncoagulation. Based on these findings, it is speculated that the pathogens capable of casing hemolymph noncoagulation syndrome in P. trituberculatus may originate from wild C. japonica. The drug resistance and probiotic antagonism test results can provide a theoretical basis for precise medication and offer insights into the development and application of probiotic preparations targeting the three pathogens.

Transcription regulation of African swine fever virus: dual role of M1249L

African swine fever virus (ASFV), which poses significant risks to the global economy, encodes a unique host-independent transcription system. This system comprises an eight-subunit RNA polymerase (vRNAP), temporally expressed transcription factors and transcript associated proteins, facilitating cross-species transmission via intermediate host. The protein composition of the virion and the presence of transcription factors in virus genome suggest existence of distinct transcription systems during viral infection. However, the precise mechanisms of transcription regulation remain elusive. Through analyses of dynamic transcriptome, vRNAP-associated components and cell-based assay, the critical role of M1249L in viral transcription regulation has been highlighted. Atomic-resolution structures of vRNAP-M1249L supercomplex, exhibiting a variety of conformations, have uncovered the dual functions of M1249L. During early transcription, M1249L could serve as multiple temporary transcription factors with C-terminal domain acting as a switcher for activation/inactivation, while during late transcription it aids in the packaging of the transcription machinery. The structural and functional characteristics of M1249L underscore its vital roles in ASFV transcription, packaging, and capsid assembly, presenting novel opportunities for therapeutic intervention.

Rigidifying the β2-α2 Loop in the Mouse Prion Protein Slows down Formation of Misfolded Oligomers.

Transmissible Spongiform Encephalopathies are fatal neurodegenerative diseases caused by the misfolding of the cellular prion protein (PrPC) into its pathological isoform (PrPSc). Efficient transmission of PrPSc occurs within the same species, but a species barrier limits interspecies transmission. While PrP structure is largely conserved among mammals, variations at the β2-α2 loop are observed, and even minor changes in the amino acid sequence of the β2-α2 loop can significantly affect transmission efficiency. The present study shows that the introduction of the elk/deer-specific amino acid substitutions at positions 169 (Ser to Asn) and 173 (Asn to Thr) into the mouse prion protein, which are associated with the structural rigidity of the β2-α2 loop, has a substantial impact on protein dynamics as well as on the misfolding pathways of the protein. Native state hydrogen-deuterium exchange studies coupled with mass spectrometry, show that the rigid loop substitutions stabilize not only the β2-α2 loop but also the C-terminal end of α3, suggesting that molecular interactions between these two segments are strengthened. Moreover, the energy difference between the native state and multiple misfolding-prone partially unfolded forms (PUFs) present at equilibrium, is increased. The decreased accessibility of the PUFs from the native state leads to a slowing down of the misfolding of the protein. The results of this study provide important insights into the early events of conformational conversion of prion protein into β-rich oligomers, and add to the evidence that the β2-α2 loop is a key determinant in prion protein aggregation.

SARS-CoV-2 surveillance in captive animals at the belo horizonte zoo, Minas Gerais, Brazil.

The pandemic caused by SARS-CoV-2 has not only affected humans but also raised concerns about its transmission to wild animals, potentially creating natural reservoirs. Understanding these dynamics is critical for preventing future pandemics and developing control strategies. This study aims to investigate the presence of SARS-CoV-2 in wild mammals at the Belo Horizonte Zoo in Brazil, analyzing the virus's evolution and zoonotic potential. The study was conducted at the Belo Horizonte Zoo, Minas Gerais, Brazil, covering a diverse population of mammals. Oropharyngeal, rectal, and nasal swabs were collected from 47 captive animals between November 2021 and March 2023. SARS-CoV-2 presence was determined using RT-PCR, and positive samples were sequenced for phylogenetic analysis. Consensus genomes were classified using Pangolin and NextClade tools, and a maximum likelihood phylogeny was inferred using IQ-Tree. Of the 47 animals tested, nine (19.1%) were positive for SARS-CoV-2. Positive samples included rectal, oropharyngeal, and nasal swabs, with the highest positivity in rectal samples. Three genomes were successfully sequenced, revealing two variants: VOC Alpha in a maned wolf (Chrysocyon brachyurus) and a fallow deer (Dama dama), and VOC Omicron in a western lowland gorilla (Gorilla gorilla gorilla). Phylogenetic analysis indicated potential human-to-animal transmission, with animal genomes clustering close to human samples from the same region. This study highlights the presence of SARS-CoV-2 in various wild mammal species at the Belo Horizonte Zoo, emphasizing the virus's zoonotic potential and the complexity of interspecies transmission. The detection of different variants suggests ongoing viral evolution and adaptation in new hosts. Continuous monitoring and genomic surveillance of SARS-CoV-2 in wildlife are essential for understanding its transmission dynamics and preventing future zoonotic outbreaks. These findings underscore the need for integrated public health strategies that include wildlife monitoring to mitigate the risks posed by emerging infectious diseases.

A Passion for Small Things and Staying Primed: My Career in Virology and Immunology.

A love of science and animals, perseverance, and happenstance propelled my career in veterinary virology and immunology. I have focused on deadly enteric and respiratory viral infections in neonatal livestock and humans with an aim to understand their prevalence, pathogenesis, interspecies transmission, and immunity and develop vaccines. Research on animal coronaviruses (CoVs), including their broad interspecies transmission, provided a foundation to understand emerging zoonotic fatal human respiratory CoVs [severe acute respiratory syndrome, Middle East respiratory syndrome, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)] and reverse zoonosis of SARS-CoV-2 to animals. A highlight of my early research was the discovery of the gut-mammary gland-sIgA axis, documenting a common mucosal immune system. The latter remains pivotal to designing maternal vaccines for passive immunity in neonates. Our discovery and innovative cell propagation of fastidious human and animal rotaviruses and caliciviruses and their infectivity in germ-free animals has provided cell-adapted and animal disease models for ongoing virologic and immunologic investigations and vaccines. Nevertheless, besides the research discoveries, my lasting legacy remains the outstanding mentees who have enriched my science and my life.

Avian influenza A (H5N1) virus in dairy cattle: origin, evolution, and cross-species transmission.

Since the emergence of highly pathogenic avian influenza virus (HPAIV) H5N1 of clade 2.3.4.4b as a novel reassortant virus from subtype H5N8, the virus has led to a massive number of outbreaks worldwide in wild and domestic birds. Compared to the parental HPAIV H5N8 clade 2.3.4.4b, the novel reassortant HPAIV H5N1 displayed an increased ability to escape species barriers and infect multiple mammalian species, including humans. The virus host range has been recently expanded to include ruminants, particularly dairy cattle in the United States, where cattle-to-cattle transmission was reported. As with the avian 2.3.4.4.b H5N1 viruses, the cattle-infecting virus was found to transmit from cattle to other contact animals including cats, raccoons, rodents, opossums, and poultry. Although replication of the virus in cows appears to be mainly confined to the mammary tissue, with high levels of viral loads detected in milk, infected cats and poultry showed severe respiratory disease, neurologic signs, and eventually died. Furthermore, several human infections with HPAIV H5N1 have also been reported in dairy farm workers and were attributed to exposures to infected dairy cattle. This is believed to represent the first mammalian-to-human transmission report of the HPAIV H5N1. Fortunately, infection in humans and cows, as opposed to other animals, appears to be mild in most cases. Nevertheless, the H5N1 bovine outbreak represents the largest outbreak of the H5N1 in a domestic mammal close to humans, increasing the risk that this already mammalian adapted H5N1 further adapts to human-to-human transmission and starts a pandemic. Herein, we discuss the epidemiology, evolution, pathogenesis, and potential impact of the recently identified HPAIV H5N1 clade 2.3.4.4b in dairy cattle in the United States. Eventually, interdisciplinary cooperation under a One Health framework is required to be able to control this ongoing HPAIV H5N1 outbreak to stop it before further expansion of its host range and geographical distribution.

The hidden role of buffalo trade network in bovine epidemic spreading.

Animal movements are a key factor in the spread of pathogens. Consequently, network analysis of animal movements is a well-developed and well-studied field. The relationships between animals facilitate the diffusion of infectious agents and, in particular, shared environments and close interactions can facilitate cross-species transmission. Cattle are often the focus of these studies since they are among the most widely distributed and traded species globally. This remains true for Italy as well, but with an important additional consideration. Indeed, another important productive reality in the peninsula is buffalo farming. These farms have an interesting characteristic: approximately two-thirds of them also rear cattle. This coexistence between cattle and buffalo could have an impact on the diffusion of pathogens. Given that buffalo farms are often overlooked in the literature, the primary goal of this work is to investigate the potential consequences of omitting buffalo from cattle network analyses. To investigate this impact, we will focus on Q fever, a disease that can infect both species and is present on the Italian territory and for which the impact of the buffalo population has not been thoroughly studied, and simulate its spread to the farms of both species through compartmental models. Our analysis reveals that despite the significant difference in network sizes, the unique characteristic of Italian buffalo farms makes the buffalo network essential for a comprehensive understanding of bovine disease dynamics in Italy.

Origin tracking of Brucella strain B. melitensis bv.3 ARQ-070 using biochemical and genomic studies.

To conduct an origin tracking and genomic study of the Brucella strain B. melitensis bv.3 ARQ-070, with the aim of addressing the challenges posed by the highly conserved genome of Brucella to conventional typing methods and to gain an understanding of the geographic distribution and interspecies transmission of this pathogen in China. Differentiation and genotyping were established via biochemical profiles and polymerase chain reaction (AMOS-PCR). Illumina MiSeq® was applied to sequence the Brucella isolates. Using multilocus sequence typing (MLST) multilocus sequence typing and Fisher's exact test was used for the KEGG enrichment analysis of differential genes. Differential gene protein PPI network analysis was conducted using the STRING database and visualisation was performed using. According to the final identification results of an A/M serum agglutination test. ARQ-070 was identified as the No. 3 white spirulina biological variety, and mM was identified as the No. 1 white Spirulina biological variety. The genetic information of this strain is very close to that of the M5 vaccine strain, suggesting possible vaccine-escape infection. In the comparative genomics analysis with B. melitensis bv.1 16M, the main differences between the B. melitensis strains were found to be concentrated in the genes related to amino acid metabolism and environmental perception. A base mutation was found in the Brucella gene virB9, which is associated with the key virulence factor of the type IV secretion system (T4SS), but this mutation did not lead to changes in the protein's tertiary structure, and the strain did not lose its infectivity. The study discovered a base mutation in the virB9 gene of Brucella, which is linked to T4SS but does not affect the protein's structure or the strain's infectivity. This mutation could influence public health approaches to detecting and preventing Brucella transmission. Future research aims to analyse a wider range of Brucella strains for a deeper understanding of their epidemiology.

Identification of the critical residues of TMPRSS2 for entry and host range of human coronavirus HKU1.

Human coronavirus (CoV) HKU1 infection typically causes common cold but can lead to pneumonia in children, older people, and immunosuppressed individuals. Recently, human transmembrane serine protease 2 (hTMPRSS2) was identified as the functional receptor for HKU1, but its region and residues critical for HKU1 S binding remain elusive. In this study, we find that HKU1 could utilize human and hamster, but not rat, mouse, or bat TMPRSS2 for virus entry, displaying a narrow host range. Using human-bat TMPRSS2 chimeras, we show that the serine peptidase (SP) domain of TMPRSS2 is essential for entry of HKU1. Further extensive mutagenesis analyses of the C-terminal regions of SP domains of human and bat TMPRSS2s identify residues 417 and 469 critical for entry of HKU1. Replacement of either D417 or Y469 with asparagine in hTMPRSS2 abolishes its abilities to mediate entry of HKU1 S pseudovirions and cell-cell fusion, whereas substitution of N417 with D or N469 with Y in bat TMPRSS2 (bTMPRSS2) renders it supporting HKU1 entry. Our findings contribute to a deeper understanding of coronavirus-receptor interactions and cross-species transmission.IMPORTANCEThe interactions of coronavirus (CoV) S proteins with their cognate receptors determine the host range and cross-species transmission potential. Recently, human transmembrane serine protease 2 (hTMPRSS2) was found to be the receptor for HKU1. Here, we show that the TMPRSS2 of hamster, but not rat, mouse, or bat, can serve as a functional entry receptor for HKU1. Moreover, swapping the residues at the positions of 417 and 469 of bTMPRSS2 with the corresponding residues of hTMPRSS2 confers it supporting entry of HKU1 S pseudovirions, indicating the critical role of these residues in HKU1 entry. Our study identified the critical residues in hTMPRSS2 responsible for receptor interaction and host range of HKU1.

A panoramic view of the molecular epidemiology, evolution, and cross-species transmission of rosaviruses

Rosavirus is a newly discovered member of the family Picornaviridae that was initially detected in wild rodents and subsequently in children with diarrhoea. Nevertheless, there is a significant gap in our understanding of the geographical distribution, phylogenetic relationships, evolutionary patterns, and transmission of rosaviruses. To address these issues, we analysed 434 rodents and shrews from five different species that were collected in southern China. Using PCR screening of faecal samples, we detected rosaviruses in Norway rats (Rattus norvegicus) and identified two previously undocumented host species: tanezumi rats (Rattus tanezumi) and Asian house shrews (Suncus murinus). Rosaviruses were particularly common in these animals, with an overall prevalence rate of 32.49% (141/434). For genetic and evolutionary analyses, we selected six representative positive samples to amplify the complete genomes of rosaviruses. Bayesian phylogenetic analysis suggested that our sequences clustered within the genus Rosavirus, where genotype B sequences are the closest relatives. The elevated nonsynonymous-to-synonymous ratios observed in rosavirus B may be attributed to relaxed selection pressures driven by virus spillover events. On the basis of the available data, it is hypothesized that the genus Rosavirus may have originated from Norway rats around the year 1339. In summary, these findings provide valuable insights into the complex evolutionary history of rosaviruses and underscore the urgent need for ongoing surveillance of this virus.

VP8 Mosaic Nanoparticles Elicit Cross-Neutralizing Immune Responses and Provide Protection Against Heterotypic Rotavirus Challenge in Mice.

Group A rotaviruses (RVA) remain one of the dominant pathogens causing diarrhea in children under 5 years of age worldwide, despite a sharp decrease of RVA-associated diarrhea and mortality since the introduction of rotavirus vaccines. The decreased effectiveness of live attenuated rotavirus vaccines, coupled with the emergence of new rotavirus genotypes and the risk of cross-species virus transmission, underscores the necessity to develop more effective and broad-spectrum rotavirus vaccines. In this study, we utilized nanoparticles coupled with the SpyCatcher-SpyTag system to effectively display the truncated VP8-1 protein. The modular display of the monovalent VP8-1 proteins markedly increased the immunogenicity of VP8-1. Furthermore, the bivalent display of VP8-1 proteins from simian rotavirus SA11 and lamb rotavirus LLR on the same particle not only increased immunogenicity against homotypic antigens but also elicited robust heterotypic immune responses and conferred effective protection against a distant heterotypic rotavirus with sequence identities of only 62%-66% in an adult mouse model. Therefore, mosaic VP8 nanoparticles could be considered as a viable strategy for the development of the next-generation broad-spectrum rotavirus vaccine.

Two novel sites determine genetic relationships between CPV-2 and FPV: an epidemiological survey of canine and feline parvoviruses in Changchun, China (2020).

Canine parvovirus (CPV-2) and feline parvovirus (FPV) cause severe hemorrhagic diarrhea disease in dogs, cats, and fur-bearing and wildlife carnivores worldwide, continuing to pose significant threats. In this study, 140 rectal swabs were collected from 70 domestic dogs and 70 cats with clinical diarrhea in veterinary clinics in Changchun during 2020. A total of 64.3% (45/70) of dogs and 55.7% (39/70) of cats tested positive for CPV-2 or FPV using colloidal gold strips. Amino acid (aa) sequence alignment of the VP2 protein from 39 CPV-2 and 36 FPV samples revealed that 79.5% (31/39) were CPV-2c, 17.9% (7/39) were a new CPV-2a, and 2.6% (1/39) were mink enteritis virus (MEV). and 8.3% (3/36) FPV from the cats was infected by CPV-2, which suggested that CPV-2c was the dominant variant in dogs and FPV was the major pathogen in cats in Changchun city. Phylogenetic relationships of VP2 genes showed that 26 parvoviruses were closely related to domestic strains previously published in China; however, 8 FPVs and CPV-JL-15/China/2020 were clustered in the lineage of South Asiatic and European countries, and 7 out of 8 FPVs were close to Italy. In addition to Q247H, I248Y, F544Y, and E/V545V/K, two novel site mutations of N23D or L630P in NS1 protein, associated with viral cross-species transmissions, were first found as a reminder of genetic relationships of CPV-2 variants and FPVs in the same branch. Thus, regular and massive virus surveillance of parvovirus is necessary to cope with its ongoing infection, circulation, mutations, and evolutions to new subtypes with strong survival abilities.

New Genotype G3 P[8] of Rotavirus Identified in a Mexican Gastroenteric Rabbit.

Rotavirus species A (RVA) is a major cause of acute viral gastroenteritis in young humans and diverse animal species. The study of the genetic characteristics of RVAs that infect rabbits (Oryctolagus cuniculus) (lapine strain [LRV]) has been limited, and, to date, the most common and epidemiologically important combinations of G/P genotypes in rabbits have been reported to be G3 P[14] and G3 P[22]. In this study, a rotavirus species A detected from an outbreak of enteritis in a Mexican commercial rabbitry was genotypically characterized. Based on sequence and phylogenetic analysis of the VP7 and VP4 genes, the strain identified in this study (C-3/15) demonstrated a G3 P[8] genotype of rotavirus, which had not previously been reported in rabbits. Moreover, both genes were closely related to human, not lapine, rotaviruses. The G3 genotype has been reported in a wide variety of hosts, including humans and rabbits, whereas the P[8] genotype has only been reported in humans. Because this combination of genotypes has never been identified in rabbits, it is proposed that the finding presented here is possibly the result of an interspecies transmission event. This is the first work to study the molecular characteristics of rotaviruses in rabbits in Mexico, as well as the identification of human G3 and P[8] genotypes in a rabbit with enteric disease.