Structure and origin of HIV type 1 DNA in persistently infected B lymphoblastoid cell lines.
The Epstein-Barr virus (EBV) and human immunodeficiency virus type 1 (HIV-1) can coinfect resting B cells, leading to EBV-carrying lymphoblastoid cell lines (LCLs) persistently infected with HIV-1. LCLs established from coinfected peripheral blood lymphocytes (PBLs) differed from LCLs derived from HIV-1-infected cell lines, in that the majority if not all of the cells expressed gp120 and a high percentage produced infectious HIV-1 after continuous passage for 6-9 months. Restriction analysis of the putative HIV-1 provirus revealed that persistently infected LCLs carried variable copies of primarily unintegrated circular and/or linear forms of HIV-1 DNA. This extrachromosomal location is strikingly different from that of the one to three copies of integrated proviral DNA deleted in persistently infected T cell and monocytic cell lines. Anti-gp120 monoclonal antibody and 3'-azido-3'-deoxythymidine (AZT) inhibited HIV-1 expression and reduced HIV-1 DNA copy number in persistently infected LCLs, supporting the hypothesis that unintegrated HIV-1 DNA accumulates primarily as a result of superinfection. We propose that the extrachromosomal location of the HIV-1 DNA contributes to the semipermissive nature of B cell infection by HIV-1.
Guan
M
M
Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Tudor
G
G
Yang
J Y
JY
Henderson
E E
EE
D000212:Acyclovir / Q000494:pharmacology; D019380:Anti-HIV Agents / Q000494:pharmacology; D001402:B-Lymphocytes / Q000821:virology*; D002460:Cell Line; D002478:Cells, Cultured; D004279:DNA, Viral / Q000737:chemistry* / Q000302:isolation & purification; D016679:Genome, Viral; D015726:Giant Cells / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D004854:Herpesvirus 4, Human / Q000502:physiology; D006801:Humans; D011533:Proviruses / Q000235:genetics / Q000502:physiology; D015183:Restriction Mapping; D015215:Zidovudine / Q000494:pharmacology
D019380:Anti-HIV Agents; D004279:DNA, Viral; D015215:Zidovudine; D000212:Acyclovir