Dendritic cells (DCs) are potent antigen-presenting cells, and their physiological localization in tissues that interactwith the external environment is important as a first barrier against pathogens such as human immunodeficiencyvirus type I (HIV-1). Several models have been proposed to explain the possible role of DCs asa 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 whetherperipheral blood DCs from HIV-1-infected individuals on virally suppressive HAART, with plasma HIV-1RNA levels of less than 50 copies/ml, carry either HIV-1 provirus and/or HIV-1 virions. Peripheral blood DCswere isolated from a cohort of 10 HIV-1-seropositive men taking suppressive HAART. In five patients, plasmacytoidand myeloid dendritic cells were isolated to attempt to identify their respective roles in HIV-1 residualdisease. Viral out-growth assays were performed in vitro, as well as gag and R/U5 polymerase chainreaction (PCR) amplification of viral RNA and DNA, respectively, from DC and peripheral blood mononuclearcell (PBMC) extracts. Fluorescence activated cell-sorting (FACS) data revealed cellular yields from 85.90to 95.18%, of relatively pure DCs isolated from patients’ PBMCs. Although HIV-1 RNA gag and DNA RU/5were detected in all PBMC samples isolated from the patients, proviral DNA and viral RNA forms were notdetected in any of the DC isolates. In addition, no replication-competent virus was demonstrated in DC cocultureassays, while virus was isolated from each patients’ CD81 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, peripheralblood DCs do not carry HIV-1 proviral DNA or viral particles attached to their surface. These populationsof peripheral blood DCs are likely not a major HIV-1 reservoir in patients on HAART with clinically undetectableplasma viral RNA.

Peripheral blood Dendritic cells are not a major reservoir for HIV type 1 in infected individuals on virally suppressive HAART

NUNNARI G;
2003-01-01

Abstract

Dendritic cells (DCs) are potent antigen-presenting cells, and their physiological localization in tissues that interactwith the external environment is important as a first barrier against pathogens such as human immunodeficiencyvirus type I (HIV-1). Several models have been proposed to explain the possible role of DCs asa 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 whetherperipheral blood DCs from HIV-1-infected individuals on virally suppressive HAART, with plasma HIV-1RNA levels of less than 50 copies/ml, carry either HIV-1 provirus and/or HIV-1 virions. Peripheral blood DCswere isolated from a cohort of 10 HIV-1-seropositive men taking suppressive HAART. In five patients, plasmacytoidand myeloid dendritic cells were isolated to attempt to identify their respective roles in HIV-1 residualdisease. Viral out-growth assays were performed in vitro, as well as gag and R/U5 polymerase chainreaction (PCR) amplification of viral RNA and DNA, respectively, from DC and peripheral blood mononuclearcell (PBMC) extracts. Fluorescence activated cell-sorting (FACS) data revealed cellular yields from 85.90to 95.18%, of relatively pure DCs isolated from patients’ PBMCs. Although HIV-1 RNA gag and DNA RU/5were detected in all PBMC samples isolated from the patients, proviral DNA and viral RNA forms were notdetected in any of the DC isolates. In addition, no replication-competent virus was demonstrated in DC cocultureassays, while virus was isolated from each patients’ CD81 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, peripheralblood DCs do not carry HIV-1 proviral DNA or viral particles attached to their surface. These populationsof peripheral blood DCs are likely not a major HIV-1 reservoir in patients on HAART with clinically undetectableplasma viral RNA.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11769/552218
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