HIV Restriction Factors and Mechanisms of Evasion

Retroviruses have long been a fertile model for discovering host-pathogen interactions and their associated biological principles and processes.These advances have not only informed fundamental concepts of viral replication and pathogenesis but have also provided novel insights into host cell biology.This is illustrated by the recent descriptions of host-encoded restriction factors that can serve as effective inhibitors of retroviral replication.Here, we review our understanding of the three restriction factors that have been widely shown to be potent inhibitors of HIV-1: namely, APOBEC3G, TRIM5a, and tetherin.In each case, we discuss how these unrelated proteins were identified, the mechanisms by which they inhibit replication, the means used by HIV-1 to evade their action, and their potential contributions to viral pathogenesis as well as inter-and intraspecies transmission.H IV-1, in common with all viruses, requires the concerted contributions of numerous positively acting cellular factors and pathways to achieve efficient replication (Bushman et al. 2009).Conversely, mammalian cells also express a number of diverse, dominantly acting proteins that are widely expressed and function in a cell-autonomous manner to suppress virus replication.These have been termed restriction factors and/or intrinsic resistance factors, and they provide an initial (or early) line of defense against infection as a component of, or even preceding, innate antiviral responses.This work discusses the most extensively described examples of such factors, focusing on their impact on HIV-1.These are the apolipoprotein