Interferon-α Subtypes As an Adjunct Therapeutic Approach for Human Immunodeficiency Virus Functional Cure

• Published in: Frontiers in immunology Vol. 9; p. 299
• Main Authors: George, Jeffy, Mattapallil, Joseph J
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 22.02.2018
• Subjects: AIDS Vaccines - pharmacology; Anti-HIV Agents - pharmacology; functional cure; HIV Infections - drug therapy; human immunodeficiency virus; human immunodeficiency virus latency; Humans; Immunology; Interferon-alpha - therapeutic use; interferon-α; interferon-α subtypes; Virus Latency - drug effects; human immunodeficiency virus; functional cure; interferon-α; human immunodeficiency virus latency; interferon-α subtypes
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2018.00299

Human immunodeficiency virus (HIV) establishes life-long latency in infected individuals. Although highly active antiretroviral therapy (HAART) has had a significant impact on the course of HIV infection leading to a better long-term outcome, the pool of latent reservoir remains substantial even under HAART. Numerous approaches have been under development with the goal of eradicating the latent HIV reservoir though with limited success. Approaches that combine immune-mediated control of HIV to activate both the innate and the adaptive immune system under suppressive therapy along with "shock and kill" drugs may lead to a better control of the reactivated virus. Interferon-α (IFN-α) is an innate cytokine that has been shown to activate intracellular defenses capable of restricting and controlling HIV. IFN-α, however, harbors numerous functional subtypes that have been reported to display different binding affinities and potency. Recent studies have suggested that certain subtypes such as IFN-α8 and IFN-α14 have potent anti-HIV activity with little or no immune activation, whereas other subtypes such as IFN-α4, IFN-α5, and IFN-α14 activate NK cells. Could these subtypes be used in combination with other strategies to reduce the latent viral reservoir? Here, we review the role of IFN-α subtypes in HIV infection and discuss the possibility that certain subtypes could be potential adjuncts to a "shock and kill" or therapeutic vaccination strategy leading to better control of the latent reservoir and subsequent functional cure.