Keeping your armour intact: how HIV-1 evades detection by the innate immune system: HIV-1 capsid controls detection of reverse transcription products by the cytosolic DNA sensor cGAS.
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.
Medical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Jonathan
J
Maelfait
Elena
E
Seiradake
Jan
J
Rehwinkel
D002213:Capsid / Q000276:immunology*; D018076:DNA, Complementary / Q000378:metabolism*; D003713:Dendritic Cells; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D015498:HIV-2 / Q000276:immunology*; D006801:Humans; D009713:Nucleotidyltransferases / Q000378:metabolism*
D018076:DNA, Complementary; D009713:Nucleotidyltransferases
CypA; HIV-1; HIV-1 capsid; cGAS; cytosolic DNA sensor; dendritic cells; innate antiviral immunity