Productive nonlytic human immunodeficiency virus type 1 replication in a newly established human leukemia cell line.
We have isolated a lymphoid cell line, MDS, from the pleural exudate of a patient with chronic myelomonocytic leukemia. The cells are biphenotypic, containing various T-cell and myeloid markers, and are surface negative for CD4 and CD8 but have low CD4 mRNA. The cells grow in suspension with a doubling time of 15 hr, have been karyotyped as trisomy 21, are negative for human immunodeficiency virus type 1 (HIV-1), and are tumorigenic in the nude mouse. We have isolated two stable HIV-1-producing cell lines, MDS-T, by transfecting MDS cells with pHXBc2, and MDS-I, by infecting MDS cells with HIV-1IIIB. In 24 hr, 1 x 10(5) MDS-T or MDS-I cells produce 46 ng of p24 per ml and reverse transcriptase that is capable of incorporating 0.2 pmol of [32P]TTP into oligo(dT).poly(A). Ultrastructural studies showed numerous mature viral particles in MDS-T and MDS-I cells that are capable of infecting T cells. HIV-1 infection could be inhibited by 25% in the MDS cells with the anti-CD4 antibody Leu 3a. For over a year MDS-T and MDS-I cells have been producing high concentrations of HIV-1 in culture. A subclone derived from the MDS cells behaves like the parent cells when transfected or infected with HIV-1. In contrast to other T-cell lines, neither phorbol 12-myristate 13-acetate nor tumor necrosis factor alpha stimulated the replication of HIV-1, whereas bromoadenosine 3',5'-cyclic monophosphate or interferon alpha caused 50% and 80% inhibition of reverse transcriptase production, respectively. These chronically infected T-cell lines are a useful model system to study the effect of anti-HIV agents and cellular factors required for HIV-1 replication.
Banerjee
R
R
Department of Neoplastic Diseases, Mount Sinai School of Medicine, New York, NY 10029.
Bekesi
J G
JG
Tarcsafalvi
A
A
Sperber
K
K
Deak
G
G
Choi
H S
HS
Paronetto
F
F
Holland
J F
JF
Acs
G
G
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000368:Aged; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D015152:Blotting, Northern; D015497:HIV-1 / Q000235:genetics / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D016130:Immunophenotyping; D015477:Leukemia, Myelomonocytic, Chronic / Q000276:immunology / Q000473:pathology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008854:Microscopy, Electron; D009190:Myelodysplastic Syndromes / Q000276:immunology / Q000473:pathology; D009368:Neoplasm Transplantation; D010957:Plasmids; D011493:Protein Kinase C / Q000378:metabolism; D011533:Proviruses / Q000235:genetics / Q000502:physiology / Q000648:ultrastructure; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic; D014162:Transfection; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D014779:Virus Replication
D015703:Antigens, CD; D012333:RNA, Messenger; D015124:8-Bromo Cyclic Adenosine Monophosphate; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate