CD4 mRNA expression in CD19-positive B cells and its suppression by the Epstein-Barr virus.
We have examined for synergy between the IIIB strain of HIV-1 and Epstein-Barr virus (EBV) during infection of a homogeneous cell type. In order to obtain a cell population consisting of a homogeneous cell type, CD19-positive B lymphocytes were purified from human tonsils by flow cytometry. CD19-positive lymphocytes did not express detectable surface CD4 antigen. However, CD4 mRNA could be detected in CD19-positive lymphocytes by reverse transcription coupled to polymerase chain reaction and by dot blot hybridization using an antisense riboprobe. Transcription of CD4 mRNA in CD19-positive lymphocytes was suppressed by infection with the B95-8 strain of EBV and lost in B95-8-transformed lymphoblastoid cell lines. In contrast, the P3HR-1K strain of EBV had no effect on the level of CD4 mRNA. HIV-1 could infect CD19-sorted B cells as measured by accumulation of reverse transcriptase and syncytia induction after coculture with SupT1 cells. HIV-1 infection of CD19-bearing lymphocytes was blocked by OKT4a antibodies. The ability of HIV-1 to replicate in CD19-positive B lymphocytes declined following preinfection with B95-8 but not with P3HR-1K. These results as well as results with an EBNA-2 expression vector suggest that down-regulation of both CD4 mRNA and HIV-1 infection in human B cells is a function of EBV nuclear antigen EBNA-2. The fact that native CD19-positive B lymphocytes express sufficient CD4 receptor mRNA to allow HIV-1 infection strengthens the possibility that HIV-1 replication in B cells directly participates in AIDS pathogenesis. In addition, infection with EBV may modulate the ability of HIV-1 to infect and establish a latent infection in B lymphocytes in co-infected individuals.
Zhang
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Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
Henderson
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D015703:Antigens, CD; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D001483:Base Sequence; D015704:CD4 Antigens / Q000096:biosynthesis* / Q000235:genetics; D015497:HIV-1 / Q000254:growth & development; D004854:Herpesvirus 4, Human; D006801:Humans; D008969:Molecular Sequence Data; D014066:Palatine Tonsil / Q000166:cytology; D012333:RNA, Messenger / Q000096:biosynthesis*; D013045:Species Specificity; D013489:Suppression, Genetic; D014158:Transcription, Genetic
D015703:Antigens, CD; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; D015704:CD4 Antigens; D012333:RNA, Messenger