This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Earlier, we identified 8 monkeys that are long-term nonprogressors (LTNP); they harbor a multiply deleted simian immunodeficiency virus (SIV), in which Rev and the Rev-Responsive Element (RRE) had been replaced with the constitutive transport element (CTE) of simian retrovirus type D (SRV/D). CTE was inserted in lieu of nef into the SIVmac239 backbone. The resulting Rev-independent nef-deleted SIV, termed Rev-ind nef SIV, critically depends on an intact CTE for viral RNA export into the cytoplasm. Even monkeys infected as neonates have tightly controlled this virus, although this age group is uniquely sensitive to pathogenic effects of viruses that are nonvirulent in adults. As such, Rev-ind nef SIV has passed a stringent safety test. We seek to dissect the host-virus dynamics of this non-pathogenic interaction and to evaluate the efficacy of Rev-ind nef SIV to protect the LTNP and monkeys infected for shorter time periods with this virus against low-dose mucosal challenges with pathogenic SIV. During the past year, we have performed a multiple low-dose intrarectal challenge study with the heterologous virus, SIVsmE660, in preparation for the challenge of the experimental animals enrolled into this study.
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