Cecilia Cheng-Mayer

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..Using a nonhuman primate model of heterosexual HIV-1 transmission, we tested whether a topical microbicide that reduces viral infectivity can potentiate the efficacy of a T-cell-based HIV vaccine...

..Further studies in this animal model should enhance our understanding of the mechanistic basis for, and obstacles to, coreceptor switch...

..These data have implications for HIV-1 transmission and infection in humans...

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..These observations in a simian model of R5-to-X4 evolution provide a mechanistic basis for the HIV-1 coreceptor switch...

..The data further support a model linking an open envelope gp120 conformation, better CD4 binding, and expansion to CXCR4 usage...

..These studies identify the gut and lymphoid tissues proximal to the genital tract as sites of robust CD8 T lymphocyte responses that contribute to containment of virus spread following vaginal transmission...

..The availability of an infectious R5 SHIV molecular clone that can be transmitted mucosally and causes disease provides an important reagent for studies of lentiviral pathogenesis and AIDS vaccine research...

..Similar observations were made in two infected macaques with coreceptor switch, providing in vivo evidence that fitness disadvantage is an obstacle to X4 emergence and expansion...

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..These findings in a unique isogenic system illustrate that coreceptor usage is the principal determinant of tissue and target cell specificity of the virus in vivo and dictates the dynamics of CD4+-T-cell depletion during SHIV infection...

..These findings help define R5 SHIV(SF162P3N) infection of rhesus macaques as a model to study the mechanistic basis, dynamics, and sites of HIV-1 coreceptor switch...

..However, the administered dose appears to impact SHIV(SF162P3N) vaginal infection outcome in an unexpected manner...

..These findings provide critical insights into a key question related to HIV pathogenesis and have important implications for the development and testing of antiviral vaccines and therapeutics...

..Envelope sequence changes accumulate principally in response to immune pressure exerted by the host, generating viral variants that can persist in the presence of a strong host immune response...

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..Research on further development of this promising compound as a candidate microbicide for the prevention of sexual HIV-1 transmission is therefore warranted...

..These results demonstrate that the absence or diminution of humoral immune responses by itself is insufficient to drive the R5-to-X4 switch and the neutralization susceptibility of the evolving viruses...

..Our data suggest that more-efficient binding of envelope gp120 to DC-SIGN could be relevant to the enhanced mucosal transmissibility of SHIV(SF162P3) compared to that of parental SHIV(SF162)...

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..However, HIV-HCV pseudotype infectivity was inhibited by a recombinant soluble form of CD81 and a mAb specific for CD81, suggesting that CD81 may be a component of a receptor complex...

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..Collectively, our data suggest that hTid-1, in association with heat shock proteins, exerts a negative regulatory effect on the NF-kappaB activity induced by various extracellular and intracellular activators including HTLV-1 Tax...

..Here we extended these studies to two additional RP monkeys with coreceptor switch and three without to confirm and identify additional factors that facilitated the process of phenotypic conversion...

..These data suggest that efficient HIV-1 replication is dependent on the ability of Nef to interact with cellular kinases and remove CD4 from the surface of infected macrophages...

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..We believe that information gained from the proposed studies will be invaluable for the design, testing and interpretation of preventive strategies against HIV infection in women. ..

..Furthermore, the findings should provide insight on the mechanism for Env-mediated immunopathogenesis and the impact of coreceptor use on these mechanistic processes. ..

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..We believe that information gained from the proposed studies will be invaluable for the design, testing and interpretation of preventive strategies against HIV infection in women. ..

..Since the outcome of SHIV infection via the mucosal route appears to be attenuated, it is possible that the type or extent of immune responses elicited by these two routes of immunization may differ. ..

..An understanding of the mechanism by which HIV-1 infects cells, and the cellular factor(s) involved, may lead to the identification of new targets for anti-viral and vaccine developments. ..

..4) Identify the first site and target cell of virus replication, and characterize the route of viral dissemination in R5 and X4 infected animals. ..

..Research efforts to establish a set of biologically relevant and extensively-characterized models should broaden the applications, and improve the predictive value of NHP studies. ..