PMID- 14709246 OWN - NLM STAT- MEDLINE DCOM- 20040412 LR - 20071114 IS - 0889-2229 (Print) IS - 0889-2229 (Linking) VI - 19 IP - 12 DP - 2003 Dec TI - Peripheral blood Dendritic cells are not a major reservoir for HIV type 1 in infected individuals on virally suppressive HAART. PG - 1097-103 AB - Dendritic cells (DCs) are potent antigen-presenting cells, and their physiological localization in tissues that interact with the external environment is important as a first barrier against pathogens such as human immunodeficiency virus type I (HIV-1). Several models have been proposed to explain the possible role of DCs as a reservoir for HIV-1 in patients on virally suppressive highly active antiretroviral therapy (HAART). However, the low yield of cell isolates has made this evaluation a difficult task. The present study analyzes whether peripheral blood DCs from HIV-1-infected individuals on virally suppressive HAART, with plasma HIV-1 RNA levels of less than 50 copies/ml, carry either HIV-1 provirus and/or HIV-1 virions. Peripheral blood DCs were isolated from a cohort of 10 HIV-1-seropositive men taking suppressive HAART. In five patients, plasmacytoid and myeloid dendritic cells were isolated to attempt to identify their respective roles in HIV-1 residual disease. Viral out-growth assays were performed in vitro, as well as gag and R/U5 polymerase chain reaction (PCR) amplification of viral RNA and DNA, respectively, from DC and peripheral blood mononuclear cell (PBMC) extracts. Fluorescence activated cell-sorting (FACS) data revealed cellular yields from 85.90 to 95.18%, of relatively pure DCs isolated from patients' PBMCs. Although HIV-1 RNA gag and DNA RU/5 were detected in all PBMC samples isolated from the patients, proviral DNA and viral RNA forms were not detected in any of the DC isolates. In addition, no replication-competent virus was demonstrated in DC coculture assays, while virus was isolated from each patients' CD8+ T-lymphocyte-depleted PBMC cocultures. Furthermore, HIV-1 gag proviral DNA was not detected in either plasmacytoid or myeloid DC subfractions. The current study suggests that in HIV-1-infected individuals treated with suppressive HAART, peripheral blood DCs do not carry HIV-1 proviral DNA or viral particles attached to their surface. These populations of peripheral blood DCs are likely not a major HIV-1 reservoir in patients on HAART with clinically undetectable plasma viral RNA. FAU - Otero, Miguel AU - Otero M AD - The Dorrance H. Hamilton Laboratories, Center for Human Virology and Biodefense, Division of Infectious Diseases and Environmental Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. FAU - Nunnari, Giuseppe AU - Nunnari G FAU - Leto, Daniela AU - Leto D FAU - Sullivan, Julie AU - Sullivan J FAU - Wang, Feng-Xiang AU - Wang FX FAU - Frank, Ian AU - Frank I FAU - Xu, Yan AU - Xu Y FAU - Patel, Charvi AU - Patel C FAU - Dornadula, Geethanjali AU - Dornadula G FAU - Kulkosky, Joseph AU - Kulkosky J FAU - Pomerantz, Roger J AU - Pomerantz RJ LA - eng GR - AI 45008/AI/NIAID NIH HHS/United States GR - AI146289/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - AIDS Res Hum Retroviruses JT - AIDS research and human retroviruses JID - 8709376 RN - 0 (Anti-HIV Agents) RN - 0 (DNA, Viral) SB - IM MH - Anti-HIV Agents/therapeutic use MH - *Antiretroviral Therapy, Highly Active MH - CD8-Positive T-Lymphocytes/immunology/virology MH - Cohort Studies MH - DNA, Viral/blood MH - Dendritic Cells/*virology MH - HIV Infections/blood/drug therapy/immunology/*virology MH - HIV-1/drug effects/isolation & purification/*physiology MH - Humans MH - Leukocytes, Mononuclear/virology EDAT- 2004/01/08 05:00 MHDA- 2004/04/13 05:00 CRDT- 2004/01/08 05:00 PHST- 2004/01/08 05:00 [pubmed] PHST- 2004/04/13 05:00 [medline] PHST- 2004/01/08 05:00 [entrez] AID - 10.1089/088922203771881194 [doi] PST - ppublish SO - AIDS Res Hum Retroviruses. 2003 Dec;19(12):1097-103. doi: 10.1089/088922203771881194.