Rev Protein of Human Immunodeficiency Virus Type 1 Affects the Stability and Transport of the Viral MRNA

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1989 Mar 1

PMID 2784208

Citations 313

Authors

B K Felber

C Cladaras

T Copeland

G N Pavlakis

Affiliations

Soon will be listed here.

Abstract

rev (trs/art) is an essential human immunodeficiency virus type 1 (HIV-1) regulatory protein. rev increases the levels of the gag- and env-producing mRNAs via a cis-acting element in the env region of HIV-1, named rev-responsive element. Our results show that rev increases the stability of the unspliced viral mRNA, while it does not affect the stability of the multiply spliced viral mRNAs that do not contain the rev-responsive element. The study of mutated proviral constructs producing mRNA that cannot be spliced revealed that the effect of rev on stability is independent of splicing. Our experiments also indicate that rev promotes the transport of the viral mRNA containing the rev-responsive element from the nucleus to the cytoplasm. The proposed functions of rev are consistent with its nuclear localization as shown by immunofluorescence. The selective effects of rev on the levels of the viral mRNA suggest a model for feedback regulation by rev leading to a steady state of viral expression.

Citing Articles

Non-AUG HIV-1 uORF translation elicits specific T cell immune response and regulates viral transcript expression.

Labaronne E, Decimo D, Bertrand L, Guiguettaz L, Sohier T, Cluet D Nat Commun. 2025; 16(1):1706.

PMID: 39966383 PMC: 11836288. DOI: 10.1038/s41467-025-56772-3.

30 years of HIV therapy: Current and future antiviral drug targets.

Nuwagaba J, Li J, Ngo B, Sutton R Virology. 2024; 603:110362.

PMID: 39705895 PMC: 11788039. DOI: 10.1016/j.virol.2024.110362.

Interferon-Regulated Expression of Cellular Splicing Factors Modulates Multiple Levels of HIV-1 Gene Expression and Replication.

Roesmann F, Muller L, Klaassen K, Hess S, Widera M Viruses. 2024; 16(6).

PMID: 38932230 PMC: 11209495. DOI: 10.3390/v16060938.

HIV-1 RNA genome packaging: it's G-rated.

Duchon A, Hu W mBio. 2024; 15(4):e0086123.

PMID: 38411060 PMC: 11005445. DOI: 10.1128/mbio.00861-23.

Binding stoichiometry and structural model of the HIV-1 Rev/importin β complex.

Spittler D, Indorato R, Boeri Erba E, Delaforge E, Signor L, Harris S Life Sci Alliance. 2022; 5(10).

PMID: 35995566 PMC: 9396022. DOI: 10.26508/lsa.202201431.

References

Laemmli U . Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970; 227(5259):680-5. DOI: 10.1038/227680a0. View

Rosen C, Terwilliger E, Dayton A, Sodroski J, Haseltine W . Intragenic cis-acting art gene-responsive sequences of the human immunodeficiency virus. Proc Natl Acad Sci U S A. 1988; 85(7):2071-5. PMC: 279930. DOI: 10.1073/pnas.85.7.2071. View

Greenberg M, Ziff E . Stimulation of 3T3 cells induces transcription of the c-fos proto-oncogene. Nature. 1984; 311(5985):433-8. DOI: 10.1038/311433a0. View

Arya S, Guo C, Josephs S, Wong-Staal F . Trans-activator gene of human T-lymphotropic virus type III (HTLV-III). Science. 1985; 229(4708):69-73. DOI: 10.1126/science.2990040. View

Sodroski J, Patarca R, Rosen C, Wong-Staal F, Haseltine W . Location of the trans-activating region on the genome of human T-cell lymphotropic virus type III. Science. 1985; 229(4708):74-7. DOI: 10.1126/science.2990041. View

Felber B, Paskalis H, Wong-Staal F, Pavlakis G . The pX protein of HTLV-I is a transcriptional activator of its long terminal repeats. Science. 1985; 229(4714):675-9. DOI: 10.1126/science.2992082. View

Seigel L, Ratner L, Josephs S, Derse D, Feinberg M, Reyes G . 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; 148(1):226-31. DOI: 10.1016/0042-6822(86)90419-8. View

Dayton A, Sodroski J, Rosen C, Goh W, Haseltine W . The trans-activator gene of the human T cell lymphotropic virus type III is required for replication. Cell. 1986; 44(6):941-7. DOI: 10.1016/0092-8674(86)90017-6. View

Fisher A, Feinberg M, Josephs S, Harper M, Marselle L, Reyes G . The trans-activator gene of HTLV-III is essential for virus replication. Nature. 1986; 320(6060):367-71. DOI: 10.1038/320367a0. View

10.

Sodroski J, Goh W, Rosen C, Dayton A, Terwilliger E, Haseltine W . A second post-transcriptional trans-activator gene required for HTLV-III replication. Nature. 1986; 321(6068):412-7. DOI: 10.1038/321412a0. View

11.

Feinberg M, Jarrett R, Aldovini A, Gallo R, Wong-Staal F . HTLV-III expression and production involve complex regulation at the levels of splicing and translation of viral RNA. Cell. 1986; 46(6):807-17. DOI: 10.1016/0092-8674(86)90062-0. View

12.

Cullen B . Trans-activation of human immunodeficiency virus occurs via a bimodal mechanism. Cell. 1986; 46(7):973-82. DOI: 10.1016/0092-8674(86)90696-3. View

13.

Wright C, Felber B, Paskalis H, Pavlakis G . Expression and characterization of the trans-activator of HTLV-III/LAV virus. Science. 1986; 234(4779):988-92. DOI: 10.1126/science.3490693. View

14.

Peterlin B, Luciw P, Barr P, Walker M . Elevated levels of mRNA can account for the trans-activation of human immunodeficiency virus. Proc Natl Acad Sci U S A. 1986; 83(24):9734-8. PMC: 387215. DOI: 10.1073/pnas.83.24.9734. View

15.

Gendelman H, Phelps W, Feigenbaum L, Ostrove J, Adachi A, Howley P . Trans-activation of the human immunodeficiency virus long terminal repeat sequence by DNA viruses. Proc Natl Acad Sci U S A. 1986; 83(24):9759-63. PMC: 387220. DOI: 10.1073/pnas.83.24.9759. View

16.

Muesing M, Smith D, Capon D . Regulation of mRNA accumulation by a human immunodeficiency virus trans-activator protein. Cell. 1987; 48(4):691-701. DOI: 10.1016/0092-8674(87)90247-9. View

17.

Knight D, Flomerfelt F, Ghrayeb J . Expression of the art/trs protein of HIV and study of its role in viral envelope synthesis. Science. 1987; 236(4803):837-40. DOI: 10.1126/science.3033827. View

18.

HAUBER J, Perkins A, Heimer E, Cullen B . Trans-activation of human immunodeficiency virus gene expression is mediated by nuclear events. Proc Natl Acad Sci U S A. 1987; 84(18):6364-8. PMC: 299076. DOI: 10.1073/pnas.84.18.6364. View

19.

Krawczyk Z, Wu C . Isolation of RNA for dot hybridization by heparin-DNase I treatment of whole cell lysate. Anal Biochem. 1987; 165(1):20-7. DOI: 10.1016/0003-2697(87)90195-3. View

20.

Felber B, Pavlakis G . A quantitative bioassay for HIV-1 based on trans-activation. Science. 1988; 239(4836):184-7. DOI: 10.1126/science.3422113. View