Type I IFN – A blunt spear in fighting HIV-1 infection

• HIV-1 components can effectively trigger an innate immune response through various Pattern Recognition Receptors.
• IFN is produced early during HIV-1 infection, but this initial response is dampened by viral escape mechanisms.
• Immune clearance is prevented and the virus replicates and spreads, while establishing a persistent infection.
• Prolonged and sustained stimulation of IFN during the chronic phase of infection drives chronic immune activation and inflammation.
• Chronic immune activation and inflammation contribute to the immunopathogenesis of progressive HIV-1 disease.

For more than 50 years, Type I Interferon (IFN) has been recognized as critical in controlling viral infections. IFN is produced downstream germ-line encoded pattern recognition receptors (PRRs) upon engagement by pathogen-associated molecular patterns (PAMPs). As a result, hundreds of different interferon-stimulated genes (ISGs) are rapidly induced, acting in both autocrine and paracrine manner to build a barrier against viral replication and spread. ISGs encode proteins with direct antiviral and immunomodulatory activities affecting both innate and adaptive immune responses. During infection with viruses, as HIV-1, that can establish a persistent infection, IFN although produced, is not able to block the initial infection and a chronic IFN-mediated immune activation/inflammation becomes a pathogenic mechanism of disease progression. This review will briefly summarize when and how IFN is produced during HIV-1 infection and the way this innate immune response is manipulated by the virus to its own advantage to drive chronic immune activation and progression to AIDS.