Making Sense of HIV Innate Sensing

摘要

Innate immune system sensing of HIV infection plays a role in multiple aspects of HIV pathology, including control of infection and killing of CD4~+ T cells. This sensing occurs in productively infected cells, nonpermissive resting CD4~+ T cells, and other cells like macrophages and dendritic cells (DCs). The HIV-1 restriction factor SAMHD1 is highly expressed in DCs and resting CD4~+ T cells and interferes with reverse transcription by reducing dNTP amounts, rendering these cells resistant to infection (Baldauf et al., 2012, Goldstone et al., 2011, Lagu-ette et al., 2011). HIV-2 encodes Vpx, an accessory protein that promotes the degradation of SAMHD-1, allowing both HIV-2 infection of DCs and innate sensing of virus in the DCs that might limit HIV-2 pathogenesis (Figure 1) (Baldauf et al., 2012). Manel et al. (2010) previously showed that when DC resistance to HIV-1 infection is circumvented by coinfection with HIV-2 or Vpx delivery via other mechanisms, HIV-1 induces an antiviral type I interferon response and DC maturation. This response is dependent on interaction of HIV-1 capsid with the cellular peptidyl-prolyl isomerase cyclophilin A (CypA), an interaction that also promotes infectivity. The interaction with CypA induces a capsid conformation change that alters viral uncoating. This could in turn affect the ability of intracellular sensors to detect the viral nucleic acid that serves as a pathogen-associated molecular pattern (PAMP).