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SAMHD1 (SAM domain- and HD domain-containing protein 1) inhibits HIV-1 infection of myeloid cells and resting CD4+ Tcells. Two lineages of primate lentiviruses, the sooty mangabey SIV (simian immunodeficiency virus) (SIVsm)/macaque SIV (SIVmac)/HIV-2 lineage and the red-capped mangabey SIV (SIVrcm) lineage, carry a SAMHD1 antagonist called Vpx. Vpx recognizes SAMHD1 and recruits a ubiquitin E3 ligase complex that is composed of CUL4 (Cullin4), DDB1 (damaged DNA-binding protein 1) and a member of the DCAF (DDB1/CUL4-associated factor) family called DCAF1. This E3 ligase complex polyubiquitinates SAMHD1, which leads to proteasomal degradation of SAMHD1. As opposed to the wellcharacterized interaction of SIVmac Vpx with human SAMHD1 and DCAF1, SIVrcm Vpx adopts a different mode of interaction with SAMHD1 of red-capped mangabeys. In the present study, we have characterized the interactions that are essential for SIVrcm Vpx-mediated degradation of rcmSAMHD1 (redcapped mangabey SAMHD1). Using mutagenesis and molecular modelling, we have determined the key role of the W23LHR26 peptide of SIVrcm Vpx in recognizing rcmSAMHD1. The amino acids Phe15, Leu36, Phe52, Arg55 and Arg56 at the N-terminal domain (NtD) of rcmSAMHD1 are involved in interaction with Vpxrcm (red-capped mangabey Vpx). The molecular model of rcmSAMHD1-NtD, Vpxrcm and C-terminal domain (CtD) of DCAF1 (DCAF1-CtD) complex reveals further that rcmSAMHD1-NtD and Vpxrcm utilize an interaction interface that is different from that used by human SAMHD1-CtD and Vpxsm. These findings provide further insights into the different modes of interaction between Vpx and SAMHD1 as the result of the 'arms race' of virus and host cell. [ABSTRACT FROM AUTHOR]

Background: Tetherin (also known as BST-2, CD317, and HM1.24) is an interferon- induced protein that blocks the release of a variety of enveloped viruses, such as retroviruses, filoviruses and herpesviruses. However, the relationship between tetherin and foamy viruses has not been clearly demonstrated. Results: In this study, we found that tetherin of human, simian, bovine or canine origin inhibits the production of infectious prototypic foamy virus (PFV). The inhibition of PFV by human tetherin is counteracted by human immunodeficiency virus type 1 (HIV-1) Vpu. Furthermore, we generated human tetherin transmembrane domain deletion mutant (delTM), glycosyl phosphatidylinositol (GPI) anchor deletion mutant (delGPI), and dimerization and glycosylation deficient mutants. Compared with wild type tetherin, the delTM and delGPI mutants only moderately inhibited PFV production. In contrast, the dimerization and glycosylation deficient mutants inhibit PFV production as efficiently as the wild type tetherin. Conclusions: These results demonstrate that tetherin inhibits the release and infectivity of PFV, and this inhibition is antagonized by HIV-1 Vpu. Both the transmembrane domain and the GPI anchor of tetherin are important for the inhibition of PFV, whereas the dimerization and the glycosylation of tetherin are dispensable. [ABSTRACT FROM AUTHOR]

Among persons born in China before 1980 and tested for vaccinia virus Tiantan strain (VVT), 28.7% (137/478) had neutralizing antibodies, 71.4% (25/35) had memory B-cell responses, and 65.7% (23/35) had memory T-cell responses to VVT. Because of cross-immunity between the viruses, these findings can help guide mpox vaccination strategies in China. [ABSTRACT FROM AUTHOR]

MOV10 has emerged as an important host antiviral factor. MOV10 not only inhibits various viruses, including human immunodeficiency virus type 1, hepatitis C virus and vesicular stomatitis virus, but also restricts the activity of retroelements long interspersed nucleotide element-1, Alu, SVA and intracisternal A particles. Here, we report that MOV10 suppresses influenza A virus infection through interacting with viral nucleoprotein (NP), sequestering viral RNP in the cytoplasm and causing the degradation of viral vRNA. The antiviral activity of MOV10 depends on the integrity of P-bodies. We also found that the antiviral activity of MOV10 is partially countered by viral NS1 protein that interferes with the interaction of MOV10 with viral NP and causes MOV10 degradation through the lysosomal pathway. Moreover, NS1-defective influenza A virus is more susceptible to MOV10 restriction. Our data not only expand the antiviral spectrum of MOV10 but also reveal the NS1 protein as the first viral antagonist of MOV10. [ABSTRACT FROM AUTHOR]

BST-2 (tetherin, CD317, and HM1.24) is induced by interferon and restricts virus release by tethering the enveloped viruses to the cell surface. The effect of BST-2 on influenza A virus (IAV) infection has been inconclusive. In the present study, we report that BST-2 diminishes the production of IAV virus-like particles (VLPs) that are generated by viral neuraminidase and hemagglutinin proteins to a much greater degree than it inhibits the production of wild-type IAV particles. This relatively weaker inhibition of IAV is associated with reduction in BST-2 levels, which is caused by the M2 protein that interacts with BST-2 and leads to down-regulation of cell surface BST-2 via the proteasomal pathway. Similarly to the viral antagonist Vpu, M2 also rescues the production of human immunodeficiency virus-1 VLPs and IAV VLPs in the presence of BST-2. Replication of wild-type and the M2-deleted viruses were both inhibited by BST-2, with the M2-deleted IAV being more restricted. These data reveal one mechanism that IAV employs to counter restriction by BST-2. [ABSTRACT FROM AUTHOR]

Background: Bovine herpesvirus 4 (BoHV-4) is a gammaherpesvirus whose genome was cloned as Bacterial Artificial Chromosome (BAC) and exploited as a gene delivery vector for vaccine purposes. Although BoHV-4 genome has been completely sequenced and its open reading frames (ORFs) structurally defined in silico, most of them are not functionally characterized. In BoHV-4 genome two major immediate early genes (IE) are present, IE1 and IE2. IE2 is an essential gene because its removal from the viral genome renders the virus unable to replicate, whereas for IE1 no many functional information are available. Results: In this work, IE1 contribution in initiating and maintaining BoHV-4 lytic replication was assessed generating a recombinant BoHV-4 genome lacking of IE1 gene, BoHV-4?IE1. In contrast to BoHV-4IE2 deleted mutant, BoHV-4?IE1 infectious replicating viral particles (IRVPs) could be reconstituted following viral DNA electroporation in permissive cells. However the titer of BoHV-4?IE1 IRVPs produced into the cell supernatant and BoHV-4?IE1 plaques size were reduced respect to BoHV-4 undeleted control. Further the impaired BoHV-4?IE1 IRVPs produced into the cell supernatant could be rescued by expressing IE1 gene product in trans, confirming the implication of IE1 in BoHV-4 lytic replication. Next, the possible role of BoHV-4IE1 as bone marrow stromal cell antigen 2 (BST-2) counteracting factor, as hypothesized by IE1 amino-terminal gene product homology with Kaposi Sarcoma Associated Herpesvirus (KSHV) K5, was excluded too. Conclusions: Although the real function of BoHV-4IE1 is still elusive, a new BoHV-4 genome gene locus as a target site for the insertion of foreign DNA and resulting in the attenuation of the virus has been revealed. These data can be considered of relevance to improve BoHV-4 gene delivery properties. [ABSTRACT FROM AUTHOR]

Background: Bovine herpesvirus 4 (BoHV-4) is a gammaherpesvirus whose genome was cloned as Bacterial Artificial Chromosome (BAC) and exploited as a gene delivery vector for vaccine purposes. Although BoHV-4 genome has been completely sequenced and its open reading frames (ORFs) structurally defined in silico, most of them are not functionally characterized. In BoHV-4 genome two major immediate early genes (IE) are present, IE1 and IE2. IE2 is an essential gene because its removal from the viral genome renders the virus unable to replicate, whereas for IE1 no many functional information are available. Results: In this work, IE1 contribution in initiating and maintaining BoHV-4 lytic replication was assessed generating a recombinant BoHV-4 genome lacking of IE1 gene, BoHV-4ΔIE1. In contrast to BoHV-4IE2 deleted mutant, BoHV-4ΔIE1 infectious replicating viral particles (IRVPs) could be reconstituted following viral DNA electroporation in permissive cells. However the titer of BoHV-4ΔIE1 IRVPs produced into the cell supernatant and BoHV-4ΔIE1 plaques size were reduced respect to BoHV-4 undeleted control. Further the impaired BoHV-4ΔIE1 IRVPs produced into the cell supernatant could be rescued by expressing IE1 gene product in trans, confirming the implication of IE1 in BoHV-4 lytic replication. Next, the possible role of BoHV-4IE1 as bone marrow stromal cell antigen 2 (BST-2) counteracting factor, as hypothesized by IE1 amino-terminal gene product homology with Kaposi Sarcoma Associated Herpesvirus (KSHV) K5, was excluded too. Conclusions: Although the real function of BoHV-4IE1 is still elusive, a new BoHV-4 genome gene locus as a target site for the insertion of foreign DNA and resulting in the attenuation of the virus has been revealed. These data can be considered of relevance to improve BoHV-4 gene delivery properties. [ABSTRACT FROM AUTHOR]

Background: BST-2 (bone marrow stromal cell antigen 2) is an interferon-inducible protein that inhibits virus release by tethering viral particles to the cell surface. This antiviral activity of BST-2 is antagonized by HIV-1 accessory protein Vpu. Vpu physically interacts with BST-2 through their mutual transmembrane (TM) domains. In this study, we utilized the BRET assay and molecular dynamics (MD) simulation method to further characterize the interaction of BST-2 and Vpu. Results: Amino acids I34, L37, P40 and L41 in the TM domain of BST-2, and L11, A18 and W22 in the TM domain of Vpu were identified to be critical for the interaction between BST-2 and Vpu. The residues P40 in the TM domain of BST-2 and L11 in the TM domain of Vpu were shown, for the first time, to be important for their interaction. Furthermore, triple-amino-acid substitutions, 14–16 (AII to VAA) and 26–28 (IIE to AAA) in Vpu TM, not the single-residue mutation, profoundly disrupted BST-2/Vpu interaction. The results of MD simulation revealed significant conformational changes of the BST-2/Vpu complex as a result of mutating P40 of BST-2 and L11, 14–16 (AII to VAA) and 26–28 (IIE to AAA) of Vpu. In addition, disrupting the interaction between BST-2 and Vpu rendered BST-2 resistant to Vpu antagonization. Conclusions: Through use of the BRET assay, we identified novel key residues P40 in the TM domain of BST-2 and L11 in the TM domain of Vpu that are important for their interaction. These results add new insights into the molecular mechanism behind BST-2 antagonization by HIV-1 Vpu. [ABSTRACT FROM AUTHOR]

An abstract of the article "The interferon-induced MxB protein inhibits an early step of HIV-1 infection" by Zhenlong Liu, Qinhua Pan, Shilei Ding, Jin Qian, Fengwen Xu, Jinming Zhou, Shan Cen, Fei Guo and Chen Liang is presented.

Interferon-induced proteins (IFPs) exert multiple functions corresponding to diverse interferon signals. However, the intracellular functions of many IFPs are not fully characterized. Here, we report that IFP35, a member of the IFP family with a molecular mass of 35 kDa, can interact with the bovine Tas (BTas) regulatory protein of bovine foamy virus (BFV). The interaction involves NID2 (IFP35/Nmi homology domain) of IFP35 and the central domain of BTas. The overexpression of IFP35 disturbs the ability of BTas to activate viral-gene transcription and inhibits viral replication. The depletion of endogenous IFP35 by interfering RNA can promote the activation of BFV, suggesting an inhibitory function of IFP35 in viral-gene expression. In addition, IFP35 can interact with the homologous regulatory protein of prototype FV and arrest viral replication and repress viral transcription. Our study suggests that IFP35 may represent a novel pathway of interferon-mediated antiviral activity in host organisms that plays a role in the maintenance of FV latency. [ABSTRACT FROM AUTHOR]