Interactions between HIV-1 and cytomegalovirus in human osteosarcoma cells carrying both viruses.
Cytomegalovirus (CMV) and the human immunodeficiency virus type 1 (HIV-1) may interact in the pathogenesis of AIDS. We compared CMV replication in human osteosarcoma (HOS) cells to that in HOS cells genetically engineered to contain an envelope-deficient HIV-1 proviral construct (designated HOS-HXG). Following acute CMV infection of each cell line, HOS-HXG cells contained higher numbers of intranuclear CMV nucleocapsids than did HOS cells. Infectious CMV could be persistently detected in culture supernatant fluids of the CMV-infected HOS-HXG cells, whereas CMV was lost over several weeks from HOS cells infected with CMV in parallel. HIV-1 CMV pseudotypes were not detected in supernatant fluids from CMV-infected HOS-HXG cells. On day 119 after CMV infection, these cultures were superinfected with HIV-1. These dually infected HOS-HXG cells produced infectious HIV-1 and exhibited markedly enhanced CMV replication compared to parental CMV-infected HOS-HXG cells. Two different HIV-1 tat gene function antagonists, Ro24-7429 and chemically modified antibodies to the Tat protein, did not inhibit the replication of CMV in either acute or persistent infections of HOS-HXG cells at concentrations that inhibited HIV-1 replication.
Margalith
M
M
Massachusetts General Hospital, Harvard Medical School, Boston 02114.
Medina
D J
DJ
Hsiung
G D
GD
Smith
B R
BR
D'Aquila
R T
RT
Kaplan
J C
JC
Bechtel
L
L
Wang
M Z
MZ
Skolnik
P R
PR
Hirsch
M S
MS
D000998:Antiviral Agents / Q000494:pharmacology; D001569:Benzodiazepines; D003587:Cytomegalovirus / Q000254:growth & development* / Q000648:ultrastructure; D004352:Drug Resistance, Microbial / Q000235:genetics; D015686:Gene Products, env / Q000235:genetics; D015696:Gene Products, tat / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development*; D006801:Humans; D009173:Mycophenolic Acid / Q000494:pharmacology; D012516:Osteosarcoma / Q000382:microbiology*; D011533:Proviruses / Q000235:genetics / Q000254:growth & development; D011758:Pyrroles; D017384:Sequence Deletion; D015163:Superinfection; D014407:Tumor Cells, Cultured; D014779:Virus Replication; D054322:tat Gene Products, Human Immunodeficiency Virus
D000998:Antiviral Agents; D015686:Gene Products, env; D015696:Gene Products, tat; D011758:Pyrroles; D054322:tat Gene Products, Human Immunodeficiency Virus; D001569:Benzodiazepines; C070024:Ro 24-7429; D009173:Mycophenolic Acid