To examine the relationship between infectivity of HIV-1 variants in dendritic cell (DC)-mediated in trans infection of T cells and plasma viral RNA levels in infected subjects.
HIV-1 was isolated from peripheral blood mononuclear cells of chronically infected individuals, typed for coreceptor usage, and viral replication were examined in monocyte-derived DCs-peripheral blood lymphocytes cocultures. The rate of p24 antigen production during the logarithmic phase of viral replication was determined by enzyme-linked immunosorbent assay. Additionally, nef variants were cloned and expressed in trans with a HIV luciferase vector and CCR5-tropic HIV-1 envelope, and infectivity was measured in DC-mediated capture-transfer assays.
Replication capacity of HIV-1 viral CCR5-tropic isolates in monocyte-derived dendritic cells-peripheral blood lymphocytes cocultures was linearly associated with the plasma viral RNA levels in a cohort of HIV-1-infected individuals exhibiting an inverse relationship between plasma viral RNA and CD4 cell count. Furthermore, infectivity activity of nef variants in context of DC-mediated enhanced infection of T cells also showed a linear relationship to plasma viral RNA levels.
These results illustrate that replication capacity of HIV-1 in DC T-cell cultures is a significant determinant of plasma viral RNA level. The data suggest that adaptation of HIV-1 to DC interactions with T cells influences the level of viral replication in the host.
From the *Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX; and †Section of Infectious Diseases, Department of Medicine, University of Texas Health Science Center at Houston School of Medicine, Houston, TX.
Received for publication May 11, 2009; accepted February 18, 2010.
Supported by National Institutes of Health grant AI047725 (to J.T.K.) and in part by the Baylor-University of Texas Houston Center for AIDS Research (AI036211).
Correspondence to: Department of Molecular Virology and Microbiology, BCM385, Room 811D, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030 (e-mail: email@example.com).