title: Dissociation of unintegrated viral DNA accumulation from single-cell lysis induced by human immunodeficiency virus type 1.
abstract: Acute cytopathic retroviral infections are accompanied by the accumulation, due to superinfection, of large amounts of unintegrated viral DNA in the cells. The cytopathic effects of human immunodeficiency virus type 1 (HIV-1) infection are specific for cells that express the CD4 viral receptor and consist of syncytium formation and single-cell lysis. Here we investigated the relationship between superinfection and single-cell lysis by HIV-1. Antiviral agents were added to C8166 or Jurkat lymphocytes after HIV-1 infection had occurred. Treatment with azidothymidine or a neutralizing anti-gp120 monoclonal antibody reduced or eliminated, respectively, the formation of unintegrated viral DNA but did not inhibit single-cell killing. Furthermore, in the infected Jurkat cells, the levels of unintegrated viral DNA peaked several days before significant single-cell lysis was observed. Essentially complete superinfection resistance was established before the occurrence of single-cell killing. These results demonstrate that single-cell lysis by HIV-1 can be dissociated from superinfection and unintegrated viral DNA accumulation. These results also indicate that single-cell killing may involve envelope glycoprotein-receptor interactions not accessible to the exterior of the cell.
authors.affiliation: Department of Cancer Biology, Harvard School of Public Health, Boston, Massachusetts 02115.
authors.forename: L
authors.initials: L
authors.lastname: Bergeron
authors.forename: J
authors.initials: J
authors.lastname: Sodroski
mesh_terms: D000911:Antibodies, Monoclonal; D015139:Blotting, Southern; D015704:CD4 Antigens / Q000276:immunology; D002478:Cells, Cultured; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004279:DNA, Viral / Q000378:metabolism*; D005434:Flow Cytometry; D015726:Giant Cells / Q000473:pathology; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015658:HIV Infections / Q000382:microbiology; D015497:HIV-1 / Q000187:drug effects / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology / Q000382:microbiology*; D015163:Superinfection / Q000382:microbiology; D015215:Zidovudine / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D004279:DNA, Viral; D015699:HIV Envelope Protein gp120; D015215:Zidovudine