An intracellular block to primate lentivirus replication

Vertebrates and retroviruses have coexisted for tens of millions of years as evidenced by the fossil record provided by endogenous retroviruses (1, 2). One might therefore predict that a degree of coevolution would have occurred resulting in the generation of host mechanisms for restricting virus spread as well as the appearance of relatively apathogenic viruses. Indeed, a number of cell-autonomous host defenses against retroviruses have been described. They include mutations of cellular receptors (3) and coreceptors (4), the expression of factors down-regulating or blocking receptors (5) as well as genes interfering with intracellular steps in viral replication (6, 7). Analysis of these genes and their modes of action, as well as the identification and subsequent characterization of novel genes with anti-retroviral activity, would be expected both to shed further light on retrovirus replication and suggest novel targets for therapeutic intervention. The latest World Health Organization (WHO) projected mortality figures for the AIDS epidemic emphasise the need for novel insights into HIV type 1 (HIV-1) replication and factors controlling its pathogenicity. Two papers in this issue of PNAS, by Cowan et al. (8) and Besnier et al. (9), represent an important step in this direction.