title: Peripheral blood Dendritic cells are not a major reservoir for HIV type 1 in infected individuals on virally suppressive HAART.
abstract: 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.
authors.affiliation: 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.
authors.forename: Miguel
authors.initials: M
authors.lastname: Otero
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Nunnari
authors.forename: Daniela
authors.initials: D
authors.lastname: Leto
authors.forename: Julie
authors.initials: J
authors.lastname: Sullivan
authors.forename: Feng-Xiang
authors.initials: FX
authors.lastname: Wang
authors.forename: Ian
authors.initials: I
authors.lastname: Frank
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Charvi
authors.initials: C
authors.lastname: Patel
authors.forename: Geethanjali
authors.initials: G
authors.lastname: Dornadula
authors.forename: Joseph
authors.initials: J
authors.lastname: Kulkosky
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Pomerantz
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D015331:Cohort Studies; D004279:DNA, Viral / Q000097:blood; D003713:Dendritic Cells / Q000821:virology*; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology
chemical_list: D019380:Anti-HIV Agents; D004279:DNA, Viral