HIV Infection of Macrophages: Implications for Pathogenesis and Cure

Abstract

Although CD4⁺ T cells represent the major reservoir of persistent HIV and SIV infection, accumulating evidence suggests that macrophages also contribute. However, investigations of the role of macrophages are often underrepresented at HIV pathogenesis and cure meetings. This was the impetus for a scientific workshop dedicated to this area of study, held in Cambridge, MA in January 2017. The workshop brought together experts in the fields of HIV/SIV immunology and virology, macrophage biology and immunology, and animal models of HIV/SIV infection to discuss the role of macrophages as a physiologically relevant viral reservoir, and the implications of macrophage infection for HIV pathogenesis and strategies for cure. While still controversial, there is an emerging theory that infected macrophages likely persist in the setting of combination antiretroviral therapy. These macrophages could then drive persistent inflammation and contribute to the viral reservoir, which indicates the importance of addressing macrophages as well as CD4⁺ T cells with future therapeutic strategies.

Keywords: HIV/SIV pathogenesis; animal models of HIV infection; macrophages; replication competent virus; viral reservoir.

Figure 1.

HIV-infected macrophage. Transmission electron microscopy picture of an HIV-infected macrophage taken by Dr. Mike Mashiba and Dr. Kathy Collins (University of Michigan).