Immediate activation fails to rescue efficient human immunodeficiency virus replication in quiescent CD4+ T cells.
Unlike activated T cells, quiescent CD4+ T cells have shown resistance to human immunodeficiency virus (HIV) infection due to a block in the early events of the viral life cycle. To further investigate the nature of this block, we infected quiescent CD4+ T cells with HIV-1(NL4-3) and immediately stimulated them. Compared to activated (prestimulated) cells, these poststimulated cells showed slightly decreased viral entry and delays in the completion of reverse transcription. However, the relative efficiency of integration was similar to that of prestimulated cells. Together, this resulted in decreased expression of tat/rev mRNA and synthesis of viral protein. Furthermore, based on cell cycle staining and BrdU incorporation, poststimulated cells expressing viral protein failed to initiate a second round of their cell cycle, independently of Vpr-mediated arrest. Together, these data demonstrate that the early stages of the HIV life cycle are inefficient in these poststimulated cells and that efficient replication cannot be induced by subsequent activation.
Vatakis
Dimitrios N
DN
David Geffen School of Medicine at UCLA, 650 Charles Young Dr. South, Box 951678, 11-934 Factor, Los Angeles, CA 90095-1678, USA.
Bristol
Gregory
G
Wilkinson
Thomas A
TA
Chow
Samson A
SA
Zack
Jerome A
JA
D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002460:Cell Line; D049109:Cell Proliferation; D015967:Gene Expression Regulation, Viral; D015683:Gene Products, gag / Q000378:metabolism; D016336:Gene Products, vpr / Q000378:metabolism; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008213:Lymphocyte Activation / Q000276:immunology*; D012367:RNA, Viral / Q000235:genetics; D048348:Reverse Transcription / Q000235:genetics; D053586:Virus Internalization; D014779:Virus Replication; D054325:vpr Gene Products, Human Immunodeficiency Virus
D015683:Gene Products, gag; D016336:Gene Products, vpr; D012367:RNA, Viral; D054325:vpr Gene Products, Human Immunodeficiency Virus