Abstract
Human immunodeficiency virus (HIV) regulates the expression of its genes temporally at the mRNA processing step. A subset of the mRNA species which encode the structural and some accessory genes contains inhibitory sequences (INS or CRS elements) which prevent nuclear export of the RNA or its utilization in the cytoplasm. Such inhibition is overridden by the interaction of a viral protein, Rev, with its RNA target sequence, RRE. The vif gene product, which is essential for virus replication in vivo, is encoded by a singly spliced mRNA, and its expression is dependent on rev in infected cells. However, INS elements have not been found in the HIV-1 vif gene itself, although such elements have been observed in Gag, Pol, and Env coding sequences. We have now identified an INS within the 5' half of HIV-2 vif which does not show any homology with cellular mRNAs or other previously identified INS and CRS elements of HIV. These results suggest that retroviral mRNAs have novel labile sequences different from those of cellular mRNAs.
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- Arya S. K., Gallo R. C. Three novel genes of human T-lymphotropic virus type III: immune reactivity of their products with sera from acquired immune deficiency syndrome patients. Proc Natl Acad Sci U S A. 1986 Apr;83(7):2209–2213. doi: 10.1073/pnas.83.7.2209. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Blanc D., Patience C., Schulz T. F., Weiss R., Spire B. Transcomplementation of VIF- HIV-1 mutants in CEM cells suggests that VIF affects late steps of the viral life cycle. Virology. 1993 Mar;193(1):186–192. doi: 10.1006/viro.1993.1114. [DOI] [PubMed] [Google Scholar]
- Bray M., Prasad S., Dubay J. W., Hunter E., Jeang K. T., Rekosh D., Hammarskjöld M. L. A small element from the Mason-Pfizer monkey virus genome makes human immunodeficiency virus type 1 expression and replication Rev-independent. Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1256–1260. doi: 10.1073/pnas.91.4.1256. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brighty D. W., Rosenberg M. A cis-acting repressive sequence that overlaps the Rev-responsive element of human immunodeficiency virus type 1 regulates nuclear retention of env mRNAs independently of known splice signals. Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8314–8318. doi: 10.1073/pnas.91.18.8314. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dayton A. I., Terwilliger E. F., Potz J., Kowalski M., Sodroski J. G., Haseltine W. A. Cis-acting sequences responsive to the rev gene product of the human immunodeficiency virus. J Acquir Immune Defic Syndr. 1988;1(5):441–452. [PubMed] [Google Scholar]
- Emerman M., Vazeux R., Peden K. The rev gene product of the human immunodeficiency virus affects envelope-specific RNA localization. Cell. 1989 Jun 30;57(7):1155–1165. doi: 10.1016/0092-8674(89)90053-6. [DOI] [PubMed] [Google Scholar]
- Fan L., Peden K. Cell-free transmission of Vif mutants of HIV-1. Virology. 1992 Sep;190(1):19–29. doi: 10.1016/0042-6822(92)91188-z. [DOI] [PubMed] [Google Scholar]
- Feinberg M. B., Jarrett R. F., Aldovini A., Gallo R. C., Wong-Staal F. HTLV-III expression and production involve complex regulation at the levels of splicing and translation of viral RNA. Cell. 1986 Sep 12;46(6):807–817. doi: 10.1016/0092-8674(86)90062-0. [DOI] [PubMed] [Google Scholar]
- Felber B. K., Drysdale C. M., Pavlakis G. N. Feedback regulation of human immunodeficiency virus type 1 expression by the Rev protein. J Virol. 1990 Aug;64(8):3734–3741. doi: 10.1128/jvi.64.8.3734-3741.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Felber B. K., Hadzopoulou-Cladaras M., Cladaras C., Copeland T., Pavlakis G. N. 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):1495–1499. doi: 10.1073/pnas.86.5.1495. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fisher A. G., Ensoli B., Ivanoff L., Chamberlain M., Petteway S., Ratner L., Gallo R. C., Wong-Staal F. The sor gene of HIV-1 is required for efficient virus transmission in vitro. Science. 1987 Aug 21;237(4817):888–893. doi: 10.1126/science.3497453. [DOI] [PubMed] [Google Scholar]
- Gabuzda D. H., Lawrence K., Langhoff E., Terwilliger E., Dorfman T., Haseltine W. A., Sodroski J. Role of vif in replication of human immunodeficiency virus type 1 in CD4+ T lymphocytes. J Virol. 1992 Nov;66(11):6489–6495. doi: 10.1128/jvi.66.11.6489-6495.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Garrett E. D., Tiley L. S., Cullen B. R. Rev activates expression of the human immunodeficiency virus type 1 vif and vpr gene products. J Virol. 1991 Mar;65(3):1653–1657. doi: 10.1128/jvi.65.3.1653-1657.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Guy B., Geist M., Dott K., Spehner D., Kieny M. P., Lecocq J. P. A specific inhibitor of cysteine proteases impairs a Vif-dependent modification of human immunodeficiency virus type 1 Env protein. J Virol. 1991 Mar;65(3):1325–1331. doi: 10.1128/jvi.65.3.1325-1331.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hadzopoulou-Cladaras M., Felber B. K., Cladaras C., Athanassopoulos A., Tse A., Pavlakis G. N. The rev (trs/art) protein of human immunodeficiency virus type 1 affects viral mRNA and protein expression via a cis-acting sequence in the env region. J Virol. 1989 Mar;63(3):1265–1274. doi: 10.1128/jvi.63.3.1265-1274.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hammarskjöld M. L., Heimer J., Hammarskjöld B., Sangwan I., Albert L., Rekosh D. Regulation of human immunodeficiency virus env expression by the rev gene product. J Virol. 1989 May;63(5):1959–1966. doi: 10.1128/jvi.63.5.1959-1966.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jones T. R., Cole M. D. Rapid cytoplasmic turnover of c-myc mRNA: requirement of the 3' untranslated sequences. Mol Cell Biol. 1987 Dec;7(12):4513–4521. doi: 10.1128/mcb.7.12.4513. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kan N. C., Franchini G., Wong-Staal F., DuBois G. C., Robey W. G., Lautenberger J. A., Papas T. S. Identification of HTLV-III/LAV sor gene product and detection of antibodies in human sera. Science. 1986 Mar 28;231(4745):1553–1555. doi: 10.1126/science.3006245. [DOI] [PubMed] [Google Scholar]
- Kim S. Y., Byrn R., Groopman J., Baltimore D. Temporal aspects of DNA and RNA synthesis during human immunodeficiency virus infection: evidence for differential gene expression. J Virol. 1989 Sep;63(9):3708–3713. doi: 10.1128/jvi.63.9.3708-3713.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Maldarelli F., Martin M. A., Strebel K. Identification of posttranscriptionally active inhibitory sequences in human immunodeficiency virus type 1 RNA: novel level of gene regulation. J Virol. 1991 Nov;65(11):5732–5743. doi: 10.1128/jvi.65.11.5732-5743.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Malim M. H., Hauber J., Le S. Y., Maizel J. V., Cullen B. R. The HIV-1 rev trans-activator acts through a structured target sequence to activate nuclear export of unspliced viral mRNA. Nature. 1989 Mar 16;338(6212):254–257. doi: 10.1038/338254a0. [DOI] [PubMed] [Google Scholar]
- Michaels F. H., Hattori N., Gallo R. C., Franchini G. The human immunodeficiency virus type 1 (HIV-1) vif protein is located in the cytoplasm of infected cells and its effect on viral replication is equivalent in HIV-2. AIDS Res Hum Retroviruses. 1993 Oct;9(10):1025–1030. doi: 10.1089/aid.1993.9.1025. [DOI] [PubMed] [Google Scholar]
- Muesing M. A., Smith D. H., Cabradilla C. D., Benton C. V., Lasky L. A., Capon D. J. Nucleic acid structure and expression of the human AIDS/lymphadenopathy retrovirus. Nature. 1985 Feb 7;313(6002):450–458. doi: 10.1038/313450a0. [DOI] [PubMed] [Google Scholar]
- Nasioulas G., Zolotukhin A. S., Tabernero C., Solomin L., Cunningham C. P., Pavlakis G. N., Felber B. K. Elements distinct from human immunodeficiency virus type 1 splice sites are responsible for the Rev dependence of env mRNA. J Virol. 1994 May;68(5):2986–2993. doi: 10.1128/jvi.68.5.2986-2993.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pothier F., Ouellet M., Julien J. P., Guérin S. L. An improved CAT assay for promoter analysis in either transgenic mice or tissue culture cells. DNA Cell Biol. 1992 Jan-Feb;11(1):83–90. doi: 10.1089/dna.1992.11.83. [DOI] [PubMed] [Google Scholar]
- Rabbitts P. H., Forster A., Stinson M. A., Rabbitts T. H. Truncation of exon 1 from the c-myc gene results in prolonged c-myc mRNa stability. EMBO J. 1985 Dec 30;4(13B):3727–3733. doi: 10.1002/j.1460-2075.1985.tb04141.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reddy T. R., Kraus G., Yamada O., Looney D. J., Suhasini M., Wong-Staal F. Comparative analyses of human immunodeficiency virus type 1 (HIV-1) and HIV-2 Vif mutants. J Virol. 1995 Jun;69(6):3549–3553. doi: 10.1128/jvi.69.6.3549-3553.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Robert-Guroff M., Popovic M., Gartner S., Markham P., Gallo R. C., Reitz M. S. Structure and expression of tat-, rev-, and nef-specific transcripts of human immunodeficiency virus type 1 in infected lymphocytes and macrophages. J Virol. 1990 Jul;64(7):3391–3398. doi: 10.1128/jvi.64.7.3391-3398.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sakai H., Shibata R., Sakuragi J., Sakuragi S., Kawamura M., Adachi A. Cell-dependent requirement of human immunodeficiency virus type 1 Vif protein for maturation of virus particles. J Virol. 1993 Mar;67(3):1663–1666. doi: 10.1128/jvi.67.3.1663-1666.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schwartz S., Felber B. K., Benko D. M., Fenyö E. M., Pavlakis G. N. Cloning and functional analysis of multiply spliced mRNA species of human immunodeficiency virus type 1. J Virol. 1990 Jun;64(6):2519–2529. doi: 10.1128/jvi.64.6.2519-2529.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schwartz S., Felber B. K., Fenyö E. M., Pavlakis G. N. Env and Vpu proteins of human immunodeficiency virus type 1 are produced from multiple bicistronic mRNAs. J Virol. 1990 Nov;64(11):5448–5456. doi: 10.1128/jvi.64.11.5448-5456.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schwartz S., Felber B. K., Pavlakis G. N. Distinct RNA sequences in the gag region of human immunodeficiency virus type 1 decrease RNA stability and inhibit expression in the absence of Rev protein. J Virol. 1992 Jan;66(1):150–159. doi: 10.1128/jvi.66.1.150-159.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schwartz S., Felber B. K., Pavlakis G. N. Expression of human immunodeficiency virus type 1 vif and vpr mRNAs is Rev-dependent and regulated by splicing. Virology. 1991 Aug;183(2):677–686. doi: 10.1016/0042-6822(91)90996-o. [DOI] [PubMed] [Google Scholar]
- Shaw G., Kamen R. A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell. 1986 Aug 29;46(5):659–667. doi: 10.1016/0092-8674(86)90341-7. [DOI] [PubMed] [Google Scholar]
- Shyu A. B., Belasco J. G., Greenberg M. E. Two distinct destabilizing elements in the c-fos message trigger deadenylation as a first step in rapid mRNA decay. Genes Dev. 1991 Feb;5(2):221–231. doi: 10.1101/gad.5.2.221. [DOI] [PubMed] [Google Scholar]
- Shyu A. B., Greenberg M. E., Belasco J. G. The c-fos transcript is targeted for rapid decay by two distinct mRNA degradation pathways. Genes Dev. 1989 Jan;3(1):60–72. doi: 10.1101/gad.3.1.60. [DOI] [PubMed] [Google Scholar]
- Sodroski J., Goh W. C., Rosen C., Dayton A., Terwilliger E., Haseltine W. A second post-transcriptional trans-activator gene required for HTLV-III replication. Nature. 1986 May 22;321(6068):412–417. doi: 10.1038/321412a0. [DOI] [PubMed] [Google Scholar]
- Strebel K., Daugherty D., Clouse K., Cohen D., Folks T., Martin M. A. The HIV 'A' (sor) gene product is essential for virus infectivity. Nature. 1987 Aug 20;328(6132):728–730. doi: 10.1038/328728a0. [DOI] [PubMed] [Google Scholar]
- Treisman R. Transient accumulation of c-fos RNA following serum stimulation requires a conserved 5' element and c-fos 3' sequences. Cell. 1985 Oct;42(3):889–902. doi: 10.1016/0092-8674(85)90285-5. [DOI] [PubMed] [Google Scholar]
- Vaishnav Y. N., Wong-Staal F. The biochemistry of AIDS. Annu Rev Biochem. 1991;60:577–630. doi: 10.1146/annurev.bi.60.070191.003045. [DOI] [PubMed] [Google Scholar]
- Wilson T., Treisman R. Removal of poly(A) and consequent degradation of c-fos mRNA facilitated by 3' AU-rich sequences. Nature. 1988 Nov 24;336(6197):396–399. doi: 10.1038/336396a0. [DOI] [PubMed] [Google Scholar]
- Wisdom R., Lee W. The protein-coding region of c-myc mRNA contains a sequence that specifies rapid mRNA turnover and induction by protein synthesis inhibitors. Genes Dev. 1991 Feb;5(2):232–243. doi: 10.1101/gad.5.2.232. [DOI] [PubMed] [Google Scholar]
- von Schwedler U., Song J., Aiken C., Trono D. Vif is crucial for human immunodeficiency virus type 1 proviral DNA synthesis in infected cells. J Virol. 1993 Aug;67(8):4945–4955. doi: 10.1128/jvi.67.8.4945-4955.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
