Viral Genome Sequence Evolution in Tissue Reservoirs as an Approach to Identifying Source of Sequestered Provirus that Rebounds after HAART Suspension

Stephen J. O'Brien, et al. Laboratory of Genomic Diversity, National Cancer Institute-Frederick, Frederick (USA)

Cessation of the triple drug HAART invariably rebounds to pre-treatment levels in patients who elect to suspend HAART.  Apparently HIV remains sequestered in protected tissue reservoirs that are resilient to drug treatment.  We know that certain reservoirs for HIV persist, particularly in macrophages, memory T-lymphocytes, and in NK-cells, however no one can say which of the thirty-odd tissues in which HIV enters is the primary reservoir. We attempt to characterize the principal reservoirs by developing tissue-specific phylogenetic signature lineages of HIV genome diversity that evolve in local regions of HIV-infected tissue collected from MACS autopsy tissues.  We replicate the study with specific sequence and phylogenetic methods in animal models; namely, SIV-infected monkeys; FIV-infected domestic cats; and FIV-infected lions.