Abstract
To examine the restriction of HIV growth in murine cells, we infected NIH 3T3 cells with HIV pseudotyped by Moloney murine leukemia virus. The virus, which carried a dominant selectable marker under the control of the HIV LTR, gave large numbers of resistant clones, showing that murine cells are permissive for HIV uncoating, reverse transcription, nuclear transport and integration. However, we found that several murine cell lines, as well as CHO cells, could not support the function of rev, the viral regulatory gene which, in human cells, induces the cytoplasmic expression of the incompletely spliced class of HIV mRNAs that encode the viral structural proteins. Transfection of the HIV-infected murine cells with a HTLV-1 rex-expressing vector failed to rescue the rev- phenotype, indicating that the block extended to rex function. Most importantly, we could complement the rev defect by fusing the infected murine with uninfected human cells. We conclude that HIV tropism is partly a consequence of a trans-acting cellular factor critical for Rev function.
MeSH Terms
Animals
Blotting, Northern
Cell Fusion
Cell Line
Gene Expression Regulation, Viral
Gene Products, rev/metabolism
Genes, rev
HIV-1/genetics,physiology
HeLa Cells/metabolism
Human T-lymphotropic virus 1/genetics
Humans
Mice
RNA, Viral/genetics
Transfection
rev Gene Products, Human Immunodeficiency Virus
Chemicals
Gene Products, rev
RNA, Viral
rev Gene Products, Human Immunodeficiency Virus
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Trono D
Whitehead Institute for Biomedical Research, Cambridge, MA 02142.
Baltimore D
References (32)
32 references, click to expand
-
Isolation and expression of an altered mouse dihydrofolate reductase cDNA.
Proc Natl Acad Sci U S A. 1983 May;80(9):2495-9
PMID: 6573667
-
Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells.
Mol Cell Biol. 1982 Sep;2(9):1044-51
PMID: 6960240
-
Epithelial mouse mammary cell line exhibiting normal morphogenesis in vivo and functional differentiation in vitro.
Proc Natl Acad Sci U S A. 1984 Jun;81(12):3756-60
PMID: 6587390
-
Construction and applications of a highly transmissible murine retrovirus shuttle vector.
Cell. 1984 Jul;37(3):1053-62
PMID: 6331674
-
AIDS retrovirus (ARV-2) clone replicates in transfected human and animal fibroblasts.
Science. 1986 May 23;232(4753):998-1001
PMID: 3010461
-
A second post-transcriptional trans-activator gene required for HTLV-III replication.
Nature. 1986 May 22-28;321(6068):412-7
PMID: 3012355
-
HTLV-III expression and production involve complex regulation at the levels of splicing and translation of viral RNA.
Cell. 1986 Sep 12;46(6):807-17
PMID: 3638988
-
The T4 gene encodes the AIDS virus receptor and is expressed in the immune system and the brain.
Cell. 1986 Nov 7;47(3):333-48
PMID: 3094962
-
Transcriptional (p40x) and post-transcriptional (p27x-III) regulators are required for the expression and replication of human T-cell leukemia virus type I genes.
Proc Natl Acad Sci U S A. 1987 Jun;84(11):3653-7
PMID: 3035544
-
High-efficiency transformation of mammalian cells by plasmid DNA.
Mol Cell Biol. 1987 Aug;7(8):2745-52
PMID: 3670292
-
Post-transcriptional regulator (rex) of HTLV-1 initiates expression of viral structural proteins but suppresses expression of regulatory proteins.
EMBO J. 1988 Feb;7(2):519-23
PMID: 2835230
-
An RNA sequence of hundreds of nucleotides at the 5' end of poliovirus RNA is involved in allowing viral protein synthesis.
J Virol. 1988 Jul;62(7):2291-9
PMID: 2836612
-
Safe and efficient generation of recombinant retroviruses with amphotropic and ecotropic host ranges.
Proc Natl Acad Sci U S A. 1988 Sep;85(17):6460-4
PMID: 3413107
-
Development of a sensitive quantitative focal assay for human immunodeficiency virus infectivity.
J Virol. 1988 Oct;62(10):3779-88
PMID: 3047430
-
Sequence requirements for nucleolar localization of human T cell leukemia virus type I pX protein, which regulates viral RNA processing.
Cell. 1988 Oct 21;55(2):197-209
PMID: 3048703
-
Functional replacement of the HIV-1 rev protein by the HTLV-1 rex protein.
Nature. 1988 Oct 20;335(6192):738-40
PMID: 3262832
-
Two cis-acting elements responsible for posttranscriptional trans-regulation of gene expression of human T-cell leukemia virus type I.
Proc Natl Acad Sci U S A. 1988 Oct;85(19):7124-8
PMID: 3174625
-
Two dominant-acting selectable markers for gene transfer studies in mammalian cells.
Proc Natl Acad Sci U S A. 1988 Nov;85(21):8047-51
PMID: 3054879
-
rev protein of human immunodeficiency virus type 1 affects the stability and transport of the viral mRNA.
Proc Natl Acad Sci U S A. 1989 Mar;86(5):1495-9
PMID: 2784208
-
Regulation of human immunodeficiency virus env expression by the rev gene product.
J Virol. 1989 May;63(5):1959-66
PMID: 2704072
-
A putative murine ecotropic retrovirus receptor gene encodes a multiple membrane-spanning protein and confers susceptibility to virus infection.
Cell. 1989 May 19;57(4):659-66
PMID: 2541919
-
HIV-1 Gag mutants can dominantly interfere with the replication of the wild-type virus.
Cell. 1989 Oct 6;59(1):113-20
PMID: 2676192
-
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
-
Expanded HIV-1 cellular tropism by phenotypic mixing with murine endogenous retroviruses.
Science. 1990 Feb 16;247(4944):848-52
PMID: 2305256
-
Human immunodeficiency virus pseudotypes with expanded cellular and species tropism.
J Virol. 1990 May;64(5):2298-308
PMID: 1691314
-
Cells nonproductively infected with HIV-1 exhibit an aberrant pattern of viral RNA expression: a molecular model for latency.
Cell. 1990 Jun 29;61(7):1271-6
PMID: 2364429
-
Subcellular localization of the human immunodeficiency virus trans-acting art gene product.
J Virol. 1988 Jul;62(7):2498-501
PMID: 2836628
-
The envelope glycoprotein of the human immunodeficiency virus binds to the immunoglobulin-like domain of CD4.
Nature. 1988 Jul 14;334(6178):159-62
PMID: 3260352
-
Immunodeficiency virus rev trans-activator modulates the expression of the viral regulatory genes.
Nature. 1988 Sep 8;335(6186):181-3
PMID: 3412474
-
Expression of a bacterial gene in mammalian cells.
Science. 1980 Sep 19;209(4463):1422-7
PMID: 6251549
-
The pseudotypic paradox.
J Gen Virol. 1982 Nov;63 (Pt 1):15-24
PMID: 6757385
-
Immunoglobulin gene transcription is activated by downstream sequence elements.
Cell. 1983 Jul;33(3):741-8
PMID: 6409419