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Dendritic Cell–Mediated HIV-1 Infection of T Cells Demonstrates a Direct Relationship to Plasma Viral RNA Levels

Arora, Reetakshi PhD*; Bull, Lara PhD; Siwak, Edward B PhD*; Thippeshappa, Rajesh MS*; Arduino, Roberto C MD; Kimata, Jason T PhD*

JAIDS Journal of Acquired Immune Deficiency Syndromes: June 1st, 2010 - Volume 54 - Issue 2 - p 115-121
doi: 10.1097/QAI.0b013e3181daaf98
Basic and Translational Science

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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: jkimata@bcm.tmc.edu).

© 2010 Lippincott Williams & Wilkins, Inc.