%0 Journal Article
%T Hitting HIV where it hides
%A Andrew I Dayton
%J Retrovirology
%D 2008
%I BioMed Central
%R 10.1186/1742-4690-5-15
%X Although antiretroviral therapy has achieved laudable successes in combating HIV, particularly since the advent of protease inhibitors in the mid 1990s, fully successful treatment remains plagued by multiple, clinically latent viral reservoirs largely impervious to antiretroviral drugs. The microbiology of clinical latency is controversial and may involve elements of viral quiescence (expression of no ¨C or a limited subset of ¨C viral genes) as well as low level viral replication in protected cell types or anatomical compartments [1]. Viral persistence has been reported in brain cells (including perivascular macrophages, parenchymal microglial cells and astrocytes), NK cells, renal tubular cells, mononuclear cells from semen, follicular dendritic cells, cells of the monocyte/macrophage lineage (recently infected monocytes and tissue macrophages) and resting CD4+ T cells, with the latter two being the best known reservoirs [2-5].Attempts at attacking the resting CD4+T cell HIV reservoir have generally involved induction (of presumably quiescent virus) with IL-2, IL-7, phorbol esters, or valproic acid [3,6,7]. Such induction approaches usually assume the activated, HIV producing cells will be killed directly by the induced virus or by the host immune system but some have attempted bolstering these effects by targeting immunotoxins to viral determinants [7]. The risk of a spreading infection by virus newly induced to replicate is generally mitigated in these scenarios by HAART.Attacking the macrophage HIV reservoir has proven a thornier issue. From the virus's standpoint macrophages are an ideal reservoir cell because they are long lived, because HIV does not kill macrophages by direct lysis, as it does CD4+T cells, and because virus production by chronically infected macrophages tends to be relatively insensitive to a variety of antiretroviral agents [8-13]. Besides hosting a significant virus reservoir, chronically infected macrophages and/or their brain counterparts,
%U http://www.retrovirology.com/content/5/1/15