AEGiS-07IAC: HHV-6 as a potential cofactor in AIDS: transcriptional activation of CD4 and induction of susceptibility to HIV-1 infection in CD8+ T lymphocytes.

7th International AIDS Conference

Florence, Italy — June 16-21, 1991

HHV-6 as a potential cofactor in AIDS: transcriptional activation of CD4 and induction of susceptibility to HIV-1 infection in CD8+ T lymphocytes.

Int Conf AIDS 1991 Jun 16-21; 7:29 (abstract no. M.A.32)
Lusso P, Malnati M, DeMaria A, Lori F, Garzino-Demo A, Arya S, Gallo RC; LTCB, NCI, Bethesda, MD

OBJECTIVE: To investigate the possible role of HHV-6 as a cofactor in AIDS and the interactions between HHV-6 and HIV-1.

METHODS: Limiting dilution cell cloning, magnetic bead separation, fluorocytometry, Northern blot, PCR, p24 Ag capture, PFA inhibition, DEAE-Dextran transfection.

RESULTS: Productive HHV-6 infection was observed in both CD3+CD4+ and CD3+CD8+ normal human T-cell populations and clones. HHV-6 significantly upregulated CD4 expression in CD4+ T cells and induced de novo expression of CD4 mRNA and proteins in CD8+ T cells. In contrast, the CD3/TCR complex was transcriptionally downregulated. Immediate early HHV-6 genes were responsible for CD4, but not CD3 regulation, as demonstrated using the viral inhibitor PFA. The HHV-6-induced CD4 enabled HIV-1 to penetrate and replicate in previously non-susceptible, normal CD8+ T cells. Analogous results were obtained on cells of different lineage origin. Data will be presented from current studies aimed to identify and clone the HHV-6 gene(s) responsible for the transcriptional activation of CD4. We are also assessing the percentage of circulating T cells that coexpress CD4 and CD8 in HIV-infected patients and whether these cells harbour HHV-6 and/or HIV-1.

CONCLUSIONS: These data indicate that mature CD8+ T cells can be induced by a naturally occurring agent to reexpress CD4 in their post-thymic life. Since CD4 is the receptor for HIV-1, HHV-6 may thus broaden the cellular host-range of HIV-1, favoring its spread in coinfected patients. These findings are consistent with the CD8+ T-cell defects documented in AIDS and further support the concept that some HHV-6 strains may enhance the pathogenic effects of HIV-1, thereby accelerating the disease progression.

Keywords: AEGIS, Antigens, CD4, CD8-Positive T-Lymphocytes, HIV Infections, Herpesvirus 6, Human, Acquired Immunodeficiency Syndrome, Antigens, CD8, HIV-1, Antigens, CD3, T-Lymphocytes, Receptors, Antigen, T-Cell, Disease Susceptibility, Antigens, Differentiation, T-Lymphocyte, HIV, Trans-Activation (Genetics), Antigens, CD, Receptors, HIV, Leu-23 antigen, CD9 antigen, Human, genetics, ICA7
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