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HIV replication: a game of hide and sense

Sauter, Daniel; Kirchhoff, Frank

Current Opinion in HIV and AIDS: March 2016 - Volume 11 - Issue 2 - p 173–181
doi: 10.1097/COH.0000000000000233
IMMUNE ACTIVATION: Edited by Irini Sereti and Marcus Altfeld

Purpose of review The goal of this review is to summarize recent progress in our understanding of innate sensing of HIV. Furthermore, we present the mechanisms that HIV has evolved to attenuate innate immune responses and discuss open questions.

Recent findings Toll-like receptors (TLRs) and various cytosolic sensors induce an antiviral interferon response upon detection of genomic HIV RNA or intermediates of reverse transcription. HIV limits activation of these sensing pathways by interfering with TLR signaling and by cloaking viral nucleic acids in the cytoplasm, before proviral dsDNA translocates into the nucleus. Furthermore, the viral accessory protein Vpu mitigates antiviral gene expression by inhibiting canonical nuclear factor kappa B (NF-κB) signaling. These evasion mechanisms, however, are imperfect and HIV infection almost inevitably triggers the activation of IRF3, NF-κB and other key transcription factors of antiviral immunity. Notably, the interplay of these processes plays a critical role in the induction of chronic inflammation that drives progression to AIDS.

Summary HIV has evolved sophisticated but imperfect mechanisms to evade and counteract innate sensing. Whether virus-induced immune activation represents merely a suboptimal adaptation of HIV to its human host or even facilitates HIV replication, for example by increasing the number of viral target cells, remains to be clarified.

Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany

Correspondence to Frank Kirchhoff, Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany. Tel: +49 731 50065150; fax: +49 731 50065153; e-mail:

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