Letter | Published:

Induction of CD4 and susceptibility to HIV-1 infection in human CD8+ T lymphocytes by human herpesvirus 6

Abstract

DURING intrathymic T-cell ontogenesis, functionally competent CD3+CD4+CD8 and CD3+CD4CD8+ T lymphocytes develop from immature CD4CD8 thymocytes after transiently acquiring a double-positive CD4+CD8+ phenotype1–3. The partition between CD4+CD8+ and CD4CD8+ T cells is generally considered to be irreversible, although a small percentage of circulating CD3+ T lymphocytes coexpressing CD4 and CD8 molecules has been identified4. It has been suggested that in CD8+ T cells the CD4 genes may be methylated and thus highly repressed5, whereas in CD4+ T cells the CDS genes are unmethylated6 and their transcription can be induced by physiological stimuli such as interleukin-4 (ref. 7). Here, we demonstrate that infection with human herpesvirus 6 (HHV-6) (ref. 8), a virus proposed as a potential cofactor in AIDS (ref. 9), dramatically upregulates the expression of CD4— the receptor for human immunodeficiency virus type-1 (HIV-1) (refs 10–12)—in a human neoplastic T-cell line. More importantly, HHV-6 induces de novo expression of CD4 messenger RNA and protein in normal mature CD8+ T lymphocytes, rendering them susceptible to infection with HIV-1. These findings demonstrate that human CD3+CD4CD8+ T lymphocytes can reacquire CD4 in the post-thymic life and elucidate a novel mechanism—receptor regulation—through which HHV-6 may positively interact with HIV-1 in coinfected patients.

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