Interactions between Tat and TAR and human immunodeficiency virus replication are facilitated by human cyclin T1 but not cyclins T2a or T2b.
The transcriptional transactivator (Tat) from the human immunodeficiency virus (HIV) does not function efficiently in Chinese hamster ovary (CHO) cells. Only somatic cell hybrids between CHO and human cells and CHO cells containing human chromosome 12 (CHO12) support high levels of Tat transactivation. This restriction was mapped to interactions between Tat and TAR. Recently, human cyclin T1 was found to increase the binding of Tat to TAR and levels of Tat transactivation in rodent cells. By combining individually with CDK9, cyclin T1 or related cyclins T2a and T2b form distinct positive transcription elongation factor b (P-TEFb) complexes. In this report, we found that of these three cyclins, only cyclin T1 is encoded on human chromosome 12 and is responsible for its effects in CHO cells. Moreover, only human cyclin T1, not mouse cyclin T1 or human cyclins T2a or T2b, supported interactions between Tat and TAR in vitro. Finally, after introducing appropriate receptors and human cyclin T1 into CHO cells, they became permissive for infection by and replication of HIV.
Department of Medicine, University of California at San Francisco, San Francisco, California 94143-0703, USA.
J
J
Wimmer
K
K
Fujinaga
R
R
Taube
T P
TP
Cujec
Y
Y
Zhu
J
J
Peng
D H
DH
Price
B M
BM
Peterlin
D000818:Animals; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism; D016466:CHO Cells; D002461:Cell Line, Transformed; D002881:Chromosomes, Human, Pair 12; D006224:Cricetinae; D056906:Cyclin T; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D015696:Gene Products, tat / Q000235:genetics / Q000378:metabolism*; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D011533:Proviruses / Q000235:genetics; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D019707:Receptors, Chemokine; D015533:Transcriptional Activation; D014779:Virus Replication; D054322:tat Gene Products, Human Immunodeficiency Virus
C503684:CCNT1 protein, human; D015704:CD4 Antigens; C503685:Ccnt1 protein, mouse; D056906:Cyclin T; D016213:Cyclins; D015696:Gene Products, tat; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D054322:tat Gene Products, Human Immunodeficiency Virus