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Dendritic cell-mediated HIV-1 infection of T cells demonstrates a direct relationship to plasma viral RNA levels



Dendritic cell-mediated HIV-1 infection of T cells demonstrates a direct relationship to plasma viral RNA levels



Journal of Acquired Immune Deficiency Syndromes 54(2): 115-121



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.

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Accession: 052484314

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PMID: 20386455


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