Infection with human immunodeficiency virus (HIV) results in the depletion of CD4+ T cells in patients with AIDS. In Science, Monroe et al. describe how quiescent T cells are killed by abortive infection with HIV. Quiescent CD4+ T cells can be infected with HIV but fail to support viral production or the establishment of latent provirus. Instead, these cells accumulate incomplete viral cDNAs, which are then recognized by IFI16, a cytosolic DNA sensor that is induced by interferon-γ. IFI16 forms active inflammasomes that cleave caspase-1 and initiates pyroptosis, contributing to HIV pathogenesis. Knockdown of IFI16 or inhibition of HIV reverse transcriptase rescues quiescent T cells from this form of cell death induced by abortive HIV infection. Thus, HIV coopts the host-cell innate response. Such killing of bystander T cells might account for much of the loss of CD4+ T cells observed in patients with AIDS.
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Dempsey, L. Killing bystander T cells. Nat Immunol 15, 222 (2014). https://doi.org/10.1038/ni.2840
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DOI: https://doi.org/10.1038/ni.2840
