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

• DOI: 10.1038/349533a0
• Publication Date: 2003-06-12T23:02:42Z
• Authors: Paolo Lusso; Andrea De Maria; Mauro Malnati; Franco Lori; Susan E. DeRocco; Michael Baseler; Robert C. Gallo
• Keywords: Antigens, Differentiation, T-Lymphocyte; Base Sequence; CD3 Complex; CD8 Antigens; Herpesvirus 6, Human; Molecular Sequence Data; Oligonucleotides; Receptors, Antigen, T-Cell; Antibodies, Monoclonal; HIV Infections; Herpesviridae Infections; In Vitro Techniques; Polymerase Chain Reaction; Cell Line; 3. Good health; Antigens, CD; T-Lymphocyte Subsets; CD4 Antigens; Humans

During intrathymic T-cell ontogenesis, functionally competent CD3+CD4+CD8- and CD3+CD4-CD8+ T lymphocytes develop from immature CD4-CD8- thymocytes after transiently acquiring a double-positive CD4+CD8+ phenotype. The partition between CD4+CD8- and CD4-CD8+ T cells is generally considered to be irreversible, although a small percentage of circulating CD3+ T lymphocytes coexpressing CD4 and CD8 molecules has been identified. It has been suggested that in CD8+ T cells the CD4 genes may be methylated and thus highly repressed, whereas in CD4+ T cells the CD8 genes are unmethylated and their transcription can be induced by physiological stimuli such as interleukin-4. Here, we demonstrate that infection with human herpesvirus 6 (HHV-6), a virus proposed as a potential cofactor in AIDS, dramatically upregulates the expression of CD4--the receptor for human immunodeficiency virus type-1 (HIV-1)--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+CD4-CD8+ 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.