IMMUNOPATHOGENESIS OF CLADE C SHIV-1157IPD3N4 IN M NEMESTRINA

University Of Washington, Seattle WA

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Abstract

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. We previously reported the rapid and substantial loss of CD4+ T cells at multiple mucosal sites in pigtailed macaques following SHIV infection. By 2-3 wks post-infection, profound depletion of CD4+CCR5+ T cells cells and CD28-CD95+ effector memory cells were observed, consistent with the R5-tropism of SHIV1157ipd3N4. Two of the three animals that were studied beyond the acute phase of infection showed persistent plasma viremia for gt 48 wks, while the remaining one controlled its plasma viral load at baseline (102 copies p ml). Cross-clade neutralizing antibodies developed in both persistently viremic animals starting at 24 weeks after infection. However, both animals developed clinical signs consistent with simian AIDS and were euthanized. In collaboration with Drs. Ruth Ruprecht and Charles Wood, we studied the evolution of viral sequences in infected pig-tailed macaques as compared to human and rhesus macaques infected with viruses bearing the same envelope gene. Preliminary results indicated that similar changes occurred in the envelope gene during the course of viral infection in all three species, lending further support to the use of macaque species as model to study HIV infection in humans.