This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Despite years of effort, an effective vaccine for HIV remains elusive. Further, considerable controversy remains with regard to the earliest virologic and immunologic events in HIV infection, and correlates of immunity to infection or disease progression, which are both critical for developing novel vaccines or immunotherapeutics for prevention or control of infection. Perhaps the greatest obstacle to designing an effective vaccine is a lack of understanding of the immune responses necessary for protection from infection and/or clearance of virus from infected hosts. Finally, early cellular and molecular events, particularly in mucosal tissues of HIV infected patients are poorly understood. The proposed studies will the initial events that occur between the transmission in the vagina and reaching the intestine (source of viral amplification) in hopes to develop strategies that may prevent virus reaching the intestine and establishing a """"""""beachhead"""""""" in the host. We are also examining the earliest immunologic events that can distinguish progressors from nonprogressors to determine early immunologic correlates of immunity. To date we have sorted cells from SIV infected animals and found that much more virus is present in CD4+CCR5+ T cells than other subsets, which may be a source of how the virus is selectively transported to the intestine. Other sorting and highly sensitive RT-PCR experiments are being performed in tissues to determine how and when virus reaches distant sites after mucosal transmission. We have also found very early changes in B7-H1 (the PD-1 ligand) occur in tissues of SIV infected macaques which may regulate the host response to infection.
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