The capsids of HIV-1 and HIV-2 determine immune detection of the viral cDNA by the innate sensor cGAS in dendritic cells - PubMed (original) (raw)
. 2013 Dec 12;39(6):1132-42.
doi: 10.1016/j.immuni.2013.11.002. Epub 2013 Nov 21.
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- PMID: 24269171
- DOI: 10.1016/j.immuni.2013.11.002
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The capsids of HIV-1 and HIV-2 determine immune detection of the viral cDNA by the innate sensor cGAS in dendritic cells
Xavier Lahaye et al. Immunity. 2013.
Free article
Abstract
HIV-2 is less pathogenic for humans than HIV-1 and might provide partial cross-protection from HIV-1-induced pathology. Although both viruses replicate in the T cells of infected patients, only HIV-2 replicates efficiently in dendritic cells (DCs) and activates innate immune pathways. How HIV is sensed in DC is unknown. Capsid-mutated HIV-2 revealed that sensing by the host requires viral cDNA synthesis, but not nuclear entry or genome integration. The HIV-1 capsid prevented viral cDNA sensing up to integration, allowing the virus to escape innate recognition. In contrast, DCs sensed capsid-mutated HIV-1 and enhanced stimulation of T cells in the absence of productive infection. Finally, we found that DC sensing of HIV-1 and HIV-2 required the DNA sensor cGAS. Thus, the HIV capsid is a determinant of innate sensing of the viral cDNA by cGAS in dendritic cells. This pathway might potentially be harnessed to develop effective vaccines against HIV-1.
Copyright © 2013 Elsevier Inc. All rights reserved.
Comment in
- Making sense of HIV innate sensing.
Cox AL, Siliciano RF. Cox AL, et al. Immunity. 2013 Dec 12;39(6):998-1000. doi: 10.1016/j.immuni.2013.11.014. Immunity. 2013. PMID: 24332027 Free PMC article. - 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.
Maelfait J, Seiradake E, Rehwinkel J. Maelfait J, et al. Bioessays. 2014 Jul;36(7):649-57. doi: 10.1002/bies.201400019. Epub 2014 Apr 29. Bioessays. 2014. PMID: 24782340 Free PMC article.
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