Vpu deficient HIV strains stimulate innate immune signaling responses in target cells.

Publication Type:

Journal Article


Journal of virology, Volume 86, Issue 16, p.8499-506 (2012)


2012, Antibody Development Core Facility, Center-Authored Paper, June 2012, Scientific Imaging Core Facility, Shared Resources, Vaccine and Infectious Disease Division


Acute virus infection induces a cell-intrinsic innate immune response comprising our first line of immunity to limit virus replication and spread but viruses have developed strategies to overcome these defenses. HIV-1 is a major public health problem, however the virus/host interactions that regulate innate immune defenses against HIV-1 are not fully defined. We have recently identified the viral protein Vpu as a key determinant responsible for HIV-1 targeting and degradation of Interferon regulatory factor (IRF)3, a central transcription factor driving host cell innate immunity. IRF3 plays a major role in pathogen recognition receptor (PRR) signaling of innate immunity to drive the expression of type I interferon (IFN) and interferon-stimulated genes (ISGs), including a variety of HIV restriction factors, that serve to limit viral replication directly and/or program adaptive immunity. Here we interrogate the cellular responses to target cell infection with Vpu deficient HIV-1 strains. Remarkably, in the absence of Vpu HIV-1 triggers a potent intracellular innate immune response that suppresses infection. Thus, HIV-1 can be recognized by PRRs within the host cell to trigger an innate immune response, and this response is only unmasked in the absence of Vpu. Vpu modulation of IRF3 therefore prevents virus induction of specific innate defense programs that could otherwise limit infection. These observations show that HIV-1 can indeed be recognized as a pathogen in infected cells, and provide a novel and effective platform for defining the native innate immune programs of target cells of HIV-1 infection.