Human chromosome-dependent and -independent pathways for HIV-2 trans-activation.
Human immunodeficiency virus (HIV types 1 and 2) replication is controlled by the interaction of viral-encoded regulatory proteins and host cellular proteins with the viral long terminal repeat (LTR). The presence of HIV-1 and HIV-2 trans-activator proteins, tat1 and tat2, respectively, greatly increases viral gene expression from their homologous LTRs. It is unclear if the cellular factors that support tat1-directed trans-activation of the HIV-1 LTR are the same for tat2 trans-activation of the HIV-2 LTR. Human-Chinese hamster ovary hybrid cell clones were used to probe for human chromosomes involved in regulating HIV-1 and HIV-2 tat-directed transactivation. DNA transfection experiments showed that the presence of human chromosome 12 in human-hamster hybrid clones was necessary for high-level tat-directed trans-activation of the HIV-1 and -2 LTR. Cross-trans-activation of the HIV-2 LTR by tat1 was found to be chromosome 12 independent. In addition, chromosome 12 did not support trans-activation of another human retrovirus (human T-cell leukemia virus type I). Our results suggest that HIV-1 and -2 have evolved to employ a cellular pathway(s) encoded on human chromosome 12 for supporting homologous tat-directed trans-activation. Trans-activation of the HIV-2 LTR by tat1 in chromosome 12-minus cells suggests that multiple cellular pathways can be recruited to trans-activate the HIV-2 LTR and that these pathways may have been important in an HIV-like progenitor virus.
Hart
C E
CE
Centers for Disease Control, Atlanta, GA 30333.
Westhafer
M A
MA
Galphin
J C
JC
Ou
C Y
CY
Bacheler
L T
LT
Petteway
S R
SR
Wasmuth
J J
JJ
Chen
I S
IS
Schochetman
G
G
D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002881:Chromosomes, Human, Pair 12; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics; D015498:HIV-2 / Q000235:genetics*; D006801:Humans; D006822:Hybrid Cells; D008969:Molecular Sequence Data; D015533:Transcriptional Activation; D014162:Transfection