Macrophage-Tropic HIV-1 Can Evolve within the Male Genital Tract (2015)

Undergraduates: Blake Hauser, Maria Bednar, Li-Hua Ping, Ronald Swanstrom

Faculty Advisor: Ronald Swanstrom
Department: Health Environmental Sciences & Engineering

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HIV-1 entry into host cells depends on the Env protein, which uses both the CD4 receptor and one of two co-receptors, CCR5 or CXCR4. All HIV-1 viruses have Env proteins that can make use of the high-density CD4 present on the surfaces of T cells to gain entry. A subset of HIV-1 Env proteins are also capable of using low densities of CD4, such as those present on macrophages. Macrophage-tropism appears to evolve within the central nervous system in subjects with severe disease. Macrophage-tropic virus is rarely detected outside of cerebrospinal fluid samples. Previously, a single macrophage-tropic virus was isolated from the semen of Subject C018. This study evaluated the ability of viruses to infect Affinofile cells, which can be induced to express variable levels of CD4. We determined the tropism of 19 additional clones from 12 viral amplicons from the subject¿¿¿s semen and four viral isolates from the patient¿¿¿s blood used as controls. Four of the semen amplicons registered as macrophage-tropic, and two additional semen amplicons expressed intermediate tropism. The remaining six amplicons are T cell-tropic. Maraviroc inhibited the infectivity of 12 amplicons, indicating that those use CCR5 to gain cell entry. TZM cells were infected in the presence and absence of soluble CD4, and amplicons showed differential infectivity confirming their tropism phenotypes. This indicates that macrophage-tropic HIV-1 virus can evolve within the genital tract of subjects with advanced disease.