Abstract
The human immunodeficiency virus type 1 (HIV-1) tat protein functions at a much lower level in rodent cells than in human cells. This species-specific difference in trans activation appears to be due to the lack of a functional homolog of a human cofactor for tat in rodent cells. Using HIV-1 long terminal repeat-driven human growth hormone as a reporter plasmid, we found that the tat-mediated trans activation functions at a level 5- to 20-fold lower in rodent cells than in human cells. Stable rodent-human hybrid cells containing only human chromosome 12 support a dramatically higher degree of trans activation. Thus, human chromosome 12 encodes a species-specific HIV-1 tat cofactor which, at least partially, restores high levels of tat-mediated trans activation. Chromosome 6 also appears to provide an additional factor which enhances HIV-1 tat-mediated trans activation in murine cells.
MeSH Terms
Animals
Cell Line
Chromosomes, Human, Pair 12
Chromosomes, Human, Pair 6
Gene Products, tat/metabolism
Growth Hormone/genetics
HIV-1/genetics
Humans
Hybrid Cells/metabolism
Mice
Plasmids
Species Specificity
Trans-Activators/metabolism
Transcriptional Activation
tat Gene Products, Human Immunodeficiency Virus
Chemicals
Gene Products, tat
Trans-Activators
tat Gene Products, Human Immunodeficiency Virus
Growth Hormone
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Newstein M
Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912.
Stanbridge E J
Casey G
Shank P R
References (23)
23 references, click to expand
-
HIV-1 TAT "activates" presynthesized RNA in the nucleus.
Cell. 1989 Jul 28;58(2):269-79
PMID: 2546679
-
Identification and characterization of a HeLa nuclear protein that specifically binds to the trans-activation-response (TAR) element of human immunodeficiency virus.
Proc Natl Acad Sci U S A. 1990 May;87(9):3624-8
PMID: 2333305
-
The location of cis-acting regulatory sequences in the human T cell lymphotropic virus type III (HTLV-III/LAV) long terminal repeat.
Cell. 1985 Jul;41(3):813-23
PMID: 2988790
-
Transactivation induced by human T-lymphotropic virus type III (HTLV III) maps to a viral sequence encoding 58 amino acids and lacks tissue specificity.
Virology. 1986 Jan 15;148(1):226-31
PMID: 3002031
-
Post-transcriptional regulation accounts for the trans-activation of the human T-lymphotropic virus type III.
Nature. 1986 Feb 13-19;319(6054):555-9
PMID: 3003584
-
The trans-activator gene of the human T cell lymphotropic virus type III is required for replication.
Cell. 1986 Mar 28;44(6):941-7
PMID: 2420471
-
The trans-activator gene of HTLV-III is essential for virus replication.
Nature. 1986 Mar 27-Apr 2;320(6060):367-71
PMID: 3007995
-
Trans-activation of human immunodeficiency virus occurs via a bimodal mechanism.
Cell. 1986 Sep 26;46(7):973-82
PMID: 3530501
-
Human growth hormone as a reporter gene in regulation studies employing transient gene expression.
Mol Cell Biol. 1986 Sep;6(9):3173-9
PMID: 3023965
-
Elevated levels of mRNA can account for the trans-activation of human immunodeficiency virus.
Proc Natl Acad Sci U S A. 1986 Dec;83(24):9734-8
PMID: 3025848
-
Trans-activation of the human immunodeficiency virus long terminal repeat sequence by DNA viruses.
Proc Natl Acad Sci U S A. 1986 Dec;83(24):9759-63
PMID: 2432602
-
Anti-termination of transcription within the long terminal repeat of HIV-1 by tat gene product.
Nature. 1987 Dec 3-9;330(6147):489-93
PMID: 2825027
-
Interactions of cellular proteins involved in the transcriptional regulation of the human immunodeficiency virus.
EMBO J. 1987 Dec 1;6(12):3761-70
PMID: 3428273
-
Transcriptional but not translational regulation of HIV-1 by the tat gene product.
Nature. 1988 Apr 7;332(6164):551-3
PMID: 2833703
-
Purification of the human immunodeficiency virus type 1 enhancer and TAR binding proteins EBP-1 and UBP-1.
EMBO J. 1988 Jul;7(7):2117-30
PMID: 3138113
-
Transcriptional activation of homologous viral long terminal repeats by the human immunodeficiency virus type 1 or the human T-cell leukemia virus type I tat proteins occurs in the absence of de novo protein synthesis.
Proc Natl Acad Sci U S A. 1988 Nov;85(21):8291-5
PMID: 2847157
-
Human immunodeficiency virus 1 tat protein binds trans-activation-responsive region (TAR) RNA in vitro.
Proc Natl Acad Sci U S A. 1989 Sep;86(18):6925-9
PMID: 2476805
-
Tat trans-activates the human immunodeficiency virus through a nascent RNA target.
Cell. 1989 Oct 20;59(2):273-82
PMID: 2478293
-
HIV-1 Tat protein increases transcriptional initiation and stabilizes elongation.
Cell. 1989 Oct 20;59(2):283-92
PMID: 2553266
-
Identification of cellular proteins that bind to the human immunodeficiency virus type 1 trans-activation-responsive TAR element RNA.
Proc Natl Acad Sci U S A. 1989 Oct;86(20):7828-32
PMID: 2510154
-
Human chromosome 12 is required for elevated HIV-1 expression in human-hamster hybrid cells.
Science. 1989 Oct 27;246(4929):488-91
PMID: 2683071
-
Monochromosomal rodent-human hybrids from microcell fusion of human lymphoblastoid cells containing an inserted dominant selectable marker.
Genomics. 1990 Feb;6(2):358-66
PMID: 2307476
-
Selective transfer of individual human chromosomes to recipient cells.
Mol Cell Biol. 1985 Jan;5(1):140-6
PMID: 3982414