Keeping your armour intact: How HIV‐1 evades detection by the innate immune system

Abstract

HIV-1 infects dendritic cells (DCs) without triggering an effective innate antiviral immune response. As a consequence, the induction of adaptive immune responses controlling virus spread is limited. In a recent issue of Immunity, Lahaye and colleagues show that intricate interactions of HIV capsid with the cellular cofactor cyclophilin A (CypA) control infection and innate immune activation in DCs. Manipulation of HIV-1 capsid to increase its affinity for CypA results in reduced virus infectivity and facilitates access of the cytosolic DNA sensor cGAS to reverse transcribed DNA. This in turn induces a strong host response. Here, we discuss these findings in the context of recent developments in innate immunity and consider the implications for disease control and vaccine design.

The ISG15-Protease USP18 Is a Pleiotropic Enhancer of HIV-1 Replication

“…In contrast, some reports describe conflicting results regarding whether the reverse-transcribed viral DNA is sensed by cGAS in macrophages and in T-cells [ 9 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ]. HIV utilizes its viral core to protect its reverse transcripts from detection by cGAS; however, the level of protection, the stability of the core, and the timing of early or accidental uncoating are under debate [ 23 , 24 , 25 ]. cGAS is recruited to the viral core in a polyglutamine-binding protein-1 (PQBP1) or non-POU (Pit-Oct-Unc) domain-containing octamer-binding protein (NONO)-dependent manner in the cytosol and nucleus, respectively, enabling cGAS to recognize the HIV-1 reverse-transcribed DNA and enhance the innate signaling in response to infection by HIV [ 26 , 27 , 28 ].…”