Viral and cellular mechanisms of the innate immune sensing of HIV

•Innate sensors can recognize HIV nucleic acids and membrane-tethered particles.•HIV proteins interact with host factors to regulate innate immune sensing of the virus.•The regulation of sensors and their responses to HIV are diverse and cell-type specific.•HIV-1 remarkably escapes several innate immune sensors.•Unrestrained triggering of sensors by HIV-1 may also contribute to pathogenesis.

HIV-1 replicates in immune cells that normally respond to incoming viruses and induce antiviral immune responses. Under this constant surveillance, how HIV-1 interacts with the host to escape immune control and causes immunopathology is still being untangled. Recently, a series of HIV-1 interactions with innate sensors of viruses expressed by immune target cells have been identified. Here, we review the HIV-1 factors that escape, engage and regulate these innate immune sensors. We discuss the general principles of these interactions as well as the remarkable cell-type specificity of the regulatory mechanisms and their resulting immune responses. Innate sensors directly intersect viral replication with immunity, and understanding their triggering, or lack thereof, improves our ability to design immune interventions.