Abstract

Human immunodeficiency virus (HIV) RNA and DNA have been isolated from patient monocytes, an immune cell population that is quite different in several aspects from the canonical T-cell viral target. Because monocytes are migratory and resilient to both natural and synthetic antiviral defenses, knowledge of the contribution of monocyte infection to ongoing viral evolution and spread in vivo is of significant interest for drug development and treatment strategies. Using single viral genome sequencing from different peripheral blood compartments and phyloanatomic statistical inference, we demonstrate that productively infected monocytes follow an evolutionary trajectory that is distinct from peripheral T cells during multiple stages of disease progression. Gene flow and selection analysis reveal plasticity in the source of monocyte infection and in the region of the HIV envelope glycoprotein that experiences selection pressure across individuals. The findings, thus, point to a potential reservoir showing a range of infection and transmission dynamics, for which the current universal, T cell-targeted treatment strategies would be inadequate.\n\nAuthor summaryHuman immunodeficiency virus is a rapidly evolving virus, allowing its genetic material to act as a fingerprint for epidemiological processes among, as well as within, individual infected hosts. In this study, sampling of viral RNA from plasma and differing infected immune cell populations from the peripheral blood was undertaken for three separate individuals in order to infer such processes. The results revealed a productively infected monocyte cell population, for which distinct selection pressures were linked to differing spatiotemporal origins of infection. In light of previous evidence of the migratory nature of these cells and resilience to both natural and synthetic antiviral defenses, this study underscores the importance of further investigation into the role of monocytes, and monocyte-rich tissues, as viral reservoirs during treatment of HIV with antiretroviral therapy.