Paul Bieniasz

..Here, I present an overview of how HIV-1 interacts with some key host cell factors during its replication cycle...

..Primate- and murine-retrovirus restriction factors have diverse and overlapping specificities, and some variants of Lv1, as well as Ref1, apparently recognize and inhibit infection by widely divergent retroviruses...

..Additional, less well characterized activities also inhibit viral replication. Here, the present understanding of these 'intrinsic' immune mechanisms is reviewed and their role in protection from retroviral infection is discussed...

..Strikingly, p21 appears to alter the fate of nuclear HIV-1 DNA, promoting the formation of circular viral DNA forms rather than functional proviruses...

..Here, I review recent progress in these three areas...

..Vpu co-localized with CD317 and inhibited these effects. Inhibition of Vpu function and consequent mobilization of tetherin's antiviral activity is a potential therapeutic strategy in HIV/AIDS...

..Moreover, tagged TRIM-CypA proteins can be fully active as restriction factors without forming cytoplasmic bodies...

..These data indicate that specific HECT ubiquitin ligases can link PPXY motifs to the VPS pathway to induce viral budding...

..Overall, highly efficient and species-specific neutralization of APOBEC3G, and less efficient neutralization of APOBEC3F, appears to be a general property of Vif proteins...

..Furthermore, considering data published recently, it appears that the interactions between DNA repair components with incoming viruses, often result in inhibition of the infection rather than cooperation toward its establishment...

..However, endogenous owl monkey TRIMCyp potently inhibited an SIV(AGM) strain. Overall, sporadic examples of intrinsic antiretroviral activity exist in this panel of TRIM proteins...

..Today, 33 million persons are living with infection by the human immunodeficiency virus type 1 (HIV-1), the causative agent of AIDS, while another 25 million have already died of this disease...

..Overall, the resurrection of this extinct infectious agent in a functional form from molecular fossils should enable studies of the molecular virology and pathogenic potential of this ancient human retrovirus...

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..Thus, this study identifies VPS37C as a functional component of mammalian ESCRT-I...

..Because it is, therefore, difficult to evolve specific sequences that confer escape from APOBEC3G, these findings may explain why lentiviruses evolved an activity that induces its destruction...

..Moreover, context-dependent L-domain function may reflect distinct requirements for host functions during the morphogenesis of different viral particles or the underlying presence of additional, as yet undiscovered L domains...

..These data indicate the existence of one or more saturable inhibitors that are polymorphic in primates and prevent HIV and SIV infection by targeting the capsid of the incoming lentivirus particle...

..These studies suggest that Tsg101 recruitment is necessary but not sufficient to account for late-budding activity exhibited by HIV-1 p6...

..These data suggest that restriction factors in human and non-human primate cells are able to recognize and block infection by multiple, widely divergent retroviruses and that the factors themselves may be related...

..Overall, these findings indicate that novel restriction factors in rodents can modulate sensitivity to specific primate lentiviruses...

..We speculate that CypA and/or CypA-related proteins affect the fate of incoming HIV-1 capsid either directly or by modulating interactions with unidentified host cell factors...

..Here, we discuss the uses and limitations of existing models and recent advances that might lead to better animal models for HIV/AIDS...

..Thus, in this model system, ubiquitin conjugation to transacting factors, not viral proteins, appears critical for ubiquitin-dependent enveloped viral particle release...

..However, the PTAP-type L domain appears to be unique in its requirement for an intact, or nearly intact, ESCRT-I complex...

..Overall, an intuitively unlikely evolutionary event has, in fact, occurred at least twice in primates and represents a striking example of convergent evolution in divergent species...

..TRIM5alpha proteins from other primates exhibited distinct restriction specificities for primate lentivirus capsids. Finally, we identified novel primate lentiviral capsids that are targeted by TRIMCyp proteins...

..These approaches allow a previously unobserved view of the genesis of individual virions and the determination of parameters of viral assembly that are inaccessible with conventional techniques...

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..Overall, these data exclude a major role for GAGs in mediating the attachment of many HIV-1 strains to target cells via interactions with virion-associated gp120 or CypA...

..With CLDN1 we have identified a novel key factor for HCV entry and a new target for antiviral drug development...

..Manipulation of HIV-1 CA recognition by restriction factors promises to advance animal models and new therapeutic strategies for HIV-1 and AIDS...

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..However, localization in large cytoplasmic bodies is not required for inhibition of N-MLV by huTRIM5alpha or for inhibition of HIV-1 by chimeric or rhTRIM5alpha...

..MA-mediated inhibition is relieved by concentration-dependent Gag multimerization and imparts a high degree of cooperativity on Gag-membrane association. This cooperativity may confer temporal and spatial regulation on HIV-1 assembly...

..Expression level and autoinhibition can be important confounding variables in studies of HIV-1 assembly and contribute to defects encountered in murine cells...

..These data indicate that TRIM5alpha can confer broad innate immunity to retrovirus infection in primate cells and is likely to be an important natural barrier to cross-species retrovirus transmission...

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..This entrapment leads to subsequent endocytosis by a Rab5a- and clathrin-dependent mechanism and intracellular sequestration of virions in endosomes...

..These results strongly suggest that CycT1 expression levels in unstimulated primary lymphocytes do not profoundly limit HIV-1 gene expression or provide an adequate mechanistic explanation for proviral latency in vivo...

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..We conclude that HIV-1 assembly is initiated and completed at the PM, and not at endosomal membranes...

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..Thus, we propose that HIV-1 expresses Vpu to counteract an IFNalpha-induced, general host defense that inhibits dissemination of enveloped virions from the surface of infected cells...

..These studies have the potential to reveal new targets for chemotherapeutic intervention in HIV disease and may make a rodent model of HIV infection feasible. ..

..These studies have the potential to reveal completely novel, host-cell targets for therapeutic blockade of the replication of HIV-1, and possibly other viruses. ..

..To spread from cell to cell they make use of cellular proteins to facilitate the release of accurately assembled virus particles. Understanding how this system works could give opportunities to intervene with targeted therapeutics. ..

..The experiments proposed herein should provide greater clarity as to how Gag proteins behave during assembly in cells. ..

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..The experiments proposed herein should provide greater clarity as to how Gag proteins behave during assembly in cells. ..

..To spread from cell to cell they make use of cellular proteins to facilitate the release of accurately assembled virus particles. Understanding how this system works could give opportunities to intervene with targeted therapeutics. ..