Use of the SHIV/macaque model of HIV infection/disease, has shown that a live SHIV vaccine, deltavpu SHIVppc, elicited long term protection against SHIV-induced AIDS. The virological parameters seen in protected animals closely parallel those in HIV-infected individuals treated with highly active anti-retroviral therapy (HAART). In these patients, viral replication is dramatically curtailed, but replication-competent virus persists at a low level in resting CD4+T cells. I will use a cohort of immunized macaques reactivatable in these cells, and whether the persistence of replication competent vaccine virus is correlated with long term immune responses. Six pig-tailed macaques, will be orally inoculated with vaccine virus. As before, the virus will replicate productively for about 14 weeks, after which virus will become undetectable in blood. I will then determine whether a reservoir of replication-competent virus is established in resting CD4+T cells. Viral-specific cellular and humoral immune responses of the animals will also be monitored throughout this investigation. Vaccinates will be immunosuppressed with prednisone and the frequency of infectious cells in PBMC monitored to determine whether the virus can reactivate.
| Silverstein, Peter S; Audus, Kenneth L; Qureshi, Nilofer et al. (2010) Lipopolysaccharide increases the expression of multidrug resistance-associated protein 1 (MRP1) in RAW 264.7 macrophages. J Neuroimmune Pharmacol 5:516-20 |
