Lanekeegan4467

lymerase (3Dpol). Our findings demonstrate for the first time that FNC is an effective broad-spectrum inhibitor for human EV pathogens. Copyright © 2020 Xu et al.Polyomaviruses (PyVs) are small DNA viruses carried by diverse vertebrates. The evolutionary relationships of viruses and hosts remain largely unclear due to very limited surveillance in sympatric communities. In order to investigate whether PyVs can transmit among different mammalian species and to identify host-switching events in the field we conducted a systematic study of a large collection of bats (n=1,083) from 29 sympatric communities across China which contained multiple species with frequent contact. PyVs were detected in 21 bat communities with 192 PyVs identified in 186 bats from 15 species within 6 families representing at least 28 newly-described PyVs. Surveillance results and phylogenetic analyses surprisingly revealed three inter-family PyV host-switching events in these sympatric bat communities two distinct PyVs were identified in two bat species in restricted geographical locations, while another PyV clustered phylogenetically with PyVs carried by bats from a different host family. Virus-hoevents of PyVs. In this study, we screened PyVs in a large number of bats in sympatric communities from diverse habitats across China. We provide evidence that cross-species bat-borne PyV transmission exists, though is limited and that host-switching events appear relatively rare during the evolutionary history of these viruses. PyVs with close genomic identities were also identified in different bat species without host-switching events. Based on these findings, we propose an evolutionary scheme for bat-borne PyVs in which limited host-switching events occur on the background of co-divergence and lineage duplication generating the viral genetic diversity in bats. Copyright © 2020 American Society for Microbiology.African swine fever (ASF) is a highly contagious hemorrhagic viral disease of domestic and wild pigs that is responsible for serious economic and production losses. It is caused by the African swine fever virus (ASFV), a large and complex icosahedral DNA virus of the Asfarviridae family. Currently, there is no effective treatment or approved vaccine against the ASFV. pS273R, a specific SUMO-1 cysteine protease, catalyzes the maturation of the pp220 and pp62 polyprotein precursors into core-shell proteins. Here, we present the crystal structure of the ASFV pS273R protease at a resolution of 2.3 angstroms. The overall structure of the pS273R protease is represented by two domains named the "core domain" and the N-terminal "arm domain". The "arm domain" contains the residues from M1 to N83, and the "core domain" contains the residues from N84 to A273. A structure analysis reveals that the "core domain" shares a high degree of structural similarity with chlamydial deubiquitinating enzyme, sentrin-specific proteast distinguishes it from other members of the SUMO protease family, while the unique "arm domain" has been proven to be essential for its hydrolytic activity. Moreover, the peptidomimetic aldehyde compounds designed to target the substrate binding pocket exert prominent inhibitory effects and can thus be used in a potential lead for anti-ASFV drug development. Copyright © 2020 American Society for Microbiology.Porcine circovirus type 2 (PCV2) is an important pathogen in swine herds, and its infection in pigs has caused severe economic losses to the pig industry worldwide. The capsid protein of PCV2 is the only structural protein that is associated with PCV2 infection and immunity. Here, we report a neutralizing monoclonal antibody (mAb), 3A5, which binds to intact PCV2 virions of PCV2a, PCV2b and PCV2d genotypes. The mAb 3A5 neutralized PCV2 by blocking viral attachment to PK15 cells. selleck kinase inhibitor To further explore the neutralization mechanism, we resolved the structure of the PCV2 virion in complex with mAb 3A5 Fab fragments by using cryo-electron microscopy (cryo-EM) single particle analysis. The binding sites were located at the topmost edges around fivefold icosahedral symmetry axes, with each footprint covering amino acids from two adjacent capsid proteins. Most of the epitope residues (15/18) are conserved among 2,273 PCV2 strains. Mutations of some amino acids within the epitope had a significant effect on the neutraliznd important information for vaccine design and therapeutic antibody development against PCV2 infections. Copyright © 2020 American Society for Microbiology.Alphaherpesviruses, including pseudorabies virus (PRV), are neuroinvasive pathogens that establish life-long latency in peripheral ganglia following the initial infection at mucosal surfaces. The establishment of latent infection and the subsequent reactivations during which newly-assembled virions are sorted into and transported anterogradely inside axons to the initial mucosal site of infection, rely on axonal bidirectional transport mediated by microtubule-based motors. Previous studies using cultured peripheral nervous system (PNS) neurons have demonstrated that KIF1A, a kinesin-3 motor, mediates the efficient axonal sorting and transport of newly-assembled PRV virions. In this study, we report that KIF1A, unlike other axonal kinesins, is an intrinsically unstable protein prone to proteasomal degradation. Interestingly, PRV infection of neuronal cells leads not only to a non-specific depletion of KIF1A mRNA, but also to an accelerated proteasomal degradation of KIF1A proteins, leading to a near depletion ipheral mucosal tissues, a process mediated by kinesin motors. Here, we unveil and characterize the underlying mechanisms for a PRV-induced, accelerated degradation of KIF1A, a kinesin-3 motor promoting the sorting and transport of PRV virions in axons. We show that PRV infection disrupts the synthesis of KIF1A, and simultaneously promotes the degradation of intrinsically unstable KIF1A proteins by proteasomes in axons. Our work implies that the timing of motor reduction after reactivation would be critical because progeny particles would have a limited time window for sorting into and transport in axons for further host-to-host spread. Copyright © 2020 American Society for Microbiology.