Biomedical subjects

D Dobrescu

Publications and source records attributed to D Dobrescu.

At least 19 recordsLinked to original sources

PubMed1995

Enhanced HIV-1 replication in V beta 12 T cells due to human cytomegalovirus in monocytes: evidence for a putative herpesvirus superantigen.

HIV-1 replicates more efficiently in cultured IL-2-dependent CD4 T cells expressing V beta 12 T cell receptors (TCRs) rather than other TCRs (Laurence et al., 1992). A viral reservoir is frequently established in V beta 12 T cells in HIV-1-infected patients. Here we show that cytomegalovirus (CMV) is responsible for V beta 12-selective HIV-1 replication that is indistinguishable from the effect of known superantigens (SAGs). This effect is dependent on direct contact of T cells with CMV-infected monocytes. CMV infection, but not ie1 or ie2 transfection, reproduces this effect in a monocytoid cell line (U937). In HIV-infected patients, the presence of CMV antibodies correlates with an HIV-1 viral load preferentially skewed to the V beta 12 subset. Together, these data suggest that a CMV gene product is responsible for a SAG-driven V beta 12-selective HIV-1 reservoir in vivo.

Acquired Immunodeficiency Syndrome↗

PubMed1995

Human immunodeficiency virus 1 reservoir in CD4+ T cells is restricted to certain V beta subsets.

The human immunodeficiency virus 1 (HIV-1) replicates more efficiently in T-cell lines expressing T-cell receptors derived from certain V beta genes, V beta 12 in particular, suggesting the effects of a superantigen. The targeted V beta 12 subset was not deleted in HIV-1-infected patients. It was therefore possible that it might represent an in vivo viral reservoir. Viral load was assessed by quantitative PCR with gag primers and with an infectivity assay to measure competent virus. It was shown that the tiny V beta 12 subset (1-2% of T cells) often has a higher viral load than other V beta subsets in infected patients. Selective HIV-1 replication in V beta 12 cells was also observed 6-8 days after in vitro infection of peripheral blood lymphocytes from normal, HIV-1 negative donors. Viral replication in targeted V beta subsets may serve to promote a biologically relevant viral reservoir.

Adult↗

PubMed1995

The HIV-1 reservoir in distinct V beta subsets of CD4 T cells: evidence for a putative superantigen.

Human immunodeficiency virus-1 (HIV-1) replicates more efficiently in T cells expressing T-cell receptors using certain V beta genes, V beta 12 in particular. This V beta specificity was consistent with an HIV-1-associated superantigen. In addition, T cell-depleted peripheral blood mononuclear cells from HIV-positive donors potently stimulated V beta 12 cell lines to proliferate in culture, but not control B beta 6.7a cell lines, thus indicating the presence of a V beta-selective mitogen. The targeted V beta subsets were not deleted. It was therefore possible that these subsets might represent a viral reservoir in vivo. Viral load was assessed by quantitative polymerase chain reaction (with HIV-1 gag primers) and with an infectivity assay to measure competent virus. It was shown that the tiny V beta 12 subset (1-2% of T cells) has a higher viral load than other V beta subsets in about 65% of infected individuals. Selective HIV-1 replication in V beta 12 cells was also observed 6-9 days after in vitro infection of peripheral blood T cells from several normal HIV-1-negative donors. In summary, a superantigen-like activity appears to promote V beta-selective HIV-1 replication in vitro and in vivo in patients infected with HIV-1. New therapeutic approaches are suggested based on these findings.

Acquired Immunodeficiency Syndrome↗

PubMed1970