White Blood Cell Subpopulation Distinguishes Natural HIV Controllers from Noncontrollers

The presence of a white blood cell subpopulation was recently demonstrated to effectively distinguish individuals capable of naturally controlling HIV infection, known as HIV controllers, from people requiring antiviral medication.

Diagram of the HIV virus. Source: NIH

The Human Immunodeficiency Virus (HIV) represents a major burden on global health, infecting approximately 37 million people worldwide and contributing to over 900,000 deaths annually. The virus causes illness by targeting and killing white blood cells known as CD4+ T cells which are essential for directing and regulating the immune response against pathogens, cancer, and other threats to survival.

If uncontrolled, HIV infection eventually leads to the Acquired Immunodeficiency Syndrome (AIDS), a state of severely deficient immunologic protection resulting from the loss of too many CD4+ T cells.

While HIV infection can be treated effectively with antiretroviral therapy (ART), the use of ART worldwide is limited by its high cost, and this treatment is not curative since some virally-infected T cells remain alive and serve as reservoirs for the virus, enabling viral propagation and disease progression after the cessation of ART. ART may also generate drug-resistant mutants which would pose a grave danger to human health.

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Therefore more effective, curative, and cheaper methods for controlling HIV infection are urgently needed. Recent research has focused on the development of HIV vaccines that foster a protective immune response using characteristics of individuals capable of immunologic HIV control without medication (“elite controllers”) as guidelines.

These HIV controllers produce highly effective neutralizing antibody, which inhibits regions of the virus important for propagation, and carry potent CD8+ T cells capable of recognizing and destroying virally-infected cells.

Recent research from Stanford University, UCSD, and Gilead Sciences has shown that individuals capable of controlling HIV naturally may also be distinguished from non-controllers by certain subpopulations of white blood cells known as Natural Killer cells (NK cells).

Using two distinct machine learning techniques, the researchers identified NK cell subpopulations that could differentiate individuals capable and incapable of controlling HIV without medication.

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Future studies could isolate and characterize the anti-HIV role of these NK cell subpopulations in greater detail and potentially lead to the incorporation of methods for activating these cells against HIV in upcoming vaccine designs.

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Pohlmeyer CW, Gonzalez VD, Irrinki A, et al. (2019) Identification of NK Cell Subpopulations That Differentiate HIV-Infected Subject Cohorts with Diverse Levels of Virus Control. Journal of Virology. DOI: 10.1128/JVI.01790-18