Microbiology Select

This issue's Microbiology Select describes recent insights into the mechanisms and consequences of viral infections, including a functional genomics screen that reports an array of previously unknown host factors required for HIV-1 infection of cultured human cells. New work also defines host factors that restrain the release of HIV-1 from cells and reveals how a class of antimicrobial peptides inhibits adenoviral infections. Other discoveries include a protein in mitochondria that modulates antiviral signaling, and evidence that a rare but dangerous form of skin cancer may have a viral origin. The human immunodeficiency virus (HIV) genome encodes a relatively meager 15 proteins and hence must rely on guile or the unknowing complicity of the host to make its way in the complex world of the host cell. Although multiple host factors have been previously implicated in individual steps of the HIV life cycle (for example cell entry, transit to the nucleus, DNA integration, replication, and budding), the recent efforts by Brass et al. (2008) provide a holistic view of HIV infection that is unprecedented in its scope. They harnessed the power of RNA interference to systematically screen for factors in the host cell that facilitate HIV infection. By conducting a large-scale screen of small interfering RNAs (siRNAs) in HeLa cells in vitro, they identify more than 250 human proteins that are needed for HIV-1 infection. This effort reveals in an unbiased fashion the cellular processes that the virus commandeers in its quest to replicate and spread, including the identification of many pathways and macromo-lecular complexes not previously implicated in HIV-1 infection. For example, the authors show that retrograde Golgi transport is involved in viral entry and that the huge Mediator complex facilitates viral transcription. Other surprises include the discovery that proteins involved in autophagy are also involved in the HIV life cycle, a connection that future work may delve into further. This work also opens the door to identifying host factors, rather than factors encoded by the virus, that might be targeted to quell HIV infection. Future efforts might determine combinations of siRNAs—simulta-neously targeting multiple steps of the viral life cycle—that provide the greatest inhibition of viral spread while minimizing deleterious effects on the host cell. Previous work has shown that HIV-1 requires an accessory protein Vpu to promote the release of virus from the surface of infected cells. HIV-1 virions from strains lacking Vpu are not shed readily and instead …