Genetic Analysis of the Human Immunodeficiency Virus Type 1 Integrase Protein

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 1994 Mar 1

PMID 8107224

Citations 75

Authors

C G Shin

B Taddeo

W A Haseltine

C M Farnet

Affiliations

Soon will be listed here.

Abstract

Single-amino-acid changes in a highly conserved central region of the human immunodeficiency virus type 1 (HIV-1) integrase protein were analyzed for their effects on viral protein synthesis, virion morphogenesis, and viral replication. Alteration of two amino acids that are invariant among retroviral integrases, D116 and E152 of HIV-1, as well as a mutation of the highly conserved amino acid S147 blocked viral replication in two CD4+ human T-cell lines. Mutations of four other highly conserved amino acids in the region had no detectable effect on viral replication, whereas mutations at two positions, N117 and Y143, resulted in viruses with a delayed-replication phenotype. Defects in virion precursor polypeptide processing, virion morphology, or viral DNA synthesis were observed for all of the replication-defective mutants, indicating that changes in integrase can have pleiotropic effects on viral replication.

Citing Articles

The C-Terminal Domain of RNase H and the C-Terminus Amino Acid Residue Regulate Virus Release and Autoprocessing of a Defective HIV-1 Possessing M50I and V151I Changes in Integrase.

Imamichi T, Chen Q, Hao M, Chang W, Yang J Viruses. 2022; 14(12).

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Emergence of Compensatory Mutations Reveals the Importance of Electrostatic Interactions between HIV-1 Integrase and Genomic RNA.

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Multimodal Functionalities of HIV-1 Integrase.

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Multivalent interactions essential for lentiviral integrase function.

Ballandras-Colas A, Chivukula V, Gruszka D, Shan Z, Singh P, Pye V Nat Commun. 2022; 13(1):2416.

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HIV-1 integrase binding to genomic RNA 5'-UTR induces local structural changes in vitro and in virio.

Liu S, Koneru P, Li W, Pathirage C, Engelman A, Kvaratskhelia M Retrovirology. 2021; 18(1):37.

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References

Gelderblom H, Hausmann E, Ozel M, Pauli G, Koch M . Fine structure of human immunodeficiency virus (HIV) and immunolocalization of structural proteins. Virology. 1987; 156(1):171-6. DOI: 10.1016/0042-6822(87)90449-1. View

Cobrinik D, Katz R, Terry R, Skalka A, Leis J . Avian sarcoma and leukosis virus pol-endonuclease recognition of the tandem long terminal repeat junction: minimum site required for cleavage is also required for viral growth. J Virol. 1987; 61(6):1999-2008. PMC: 254209. DOI: 10.1128/JVI.61.6.1999-2008.1987. View

Kunkel T, Roberts J, Zakour R . Rapid and efficient site-specific mutagenesis without phenotypic selection. Methods Enzymol. 1987; 154:367-82. DOI: 10.1016/0076-6879(87)54085-x. View

Colicelli J, Goff S . Sequence and spacing requirements of a retrovirus integration site. J Mol Biol. 1988; 199(1):47-59. DOI: 10.1016/0022-2836(88)90378-6. View

Felsenstein K, Goff S . Expression of the gag-pol fusion protein of Moloney murine leukemia virus without gag protein does not induce virion formation or proteolytic processing. J Virol. 1988; 62(6):2179-82. PMC: 253323. DOI: 10.1128/JVI.62.6.2179-2182.1988. View

Quinn T, Grandgenett D . Genetic evidence that the avian retrovirus DNA endonuclease domain of pol is necessary for viral integration. J Virol. 1988; 62(7):2307-12. PMC: 253383. DOI: 10.1128/JVI.62.7.2307-2312.1988. View

Donehower L . Analysis of mutant Moloney murine leukemia viruses containing linker insertion mutations in the 3' region of pol. J Virol. 1988; 62(11):3958-64. PMC: 253822. DOI: 10.1128/JVI.62.11.3958-3964.1988. View

Dayton A, Terwilliger E, Potz J, Kowalski M, Sodroski J, Haseltine W . Cis-acting sequences responsive to the rev gene product of the human immunodeficiency virus. J Acquir Immune Defic Syndr (1988). 1988; 1(5):441-52. View

Clavel F, HOGGAN M, Willey R, Strebel K, Martin M, Repaske R . Genetic recombination of human immunodeficiency virus. J Virol. 1989; 63(3):1455-9. PMC: 247851. DOI: 10.1128/JVI.63.3.1455-1459.1989. View

10.

Navia M, Fitzgerald P, McKeever B, Leu C, Heimbach J, Herber W . Three-dimensional structure of aspartyl protease from human immunodeficiency virus HIV-1. Nature. 1989; 337(6208):615-20. DOI: 10.1038/337615a0. View

11.

Doolittle R, Feng D, Johnson M, McClure M . Origins and evolutionary relationships of retroviruses. Q Rev Biol. 1989; 64(1):1-30. DOI: 10.1086/416128. View

12.

Peng C, Ho B, Chang T, Chang N . Role of human immunodeficiency virus type 1-specific protease in core protein maturation and viral infectivity. J Virol. 1989; 63(6):2550-6. PMC: 250724. DOI: 10.1128/JVI.63.6.2550-2556.1989. View

13.

Kim S, 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; 63(9):3708-13. PMC: 250962. DOI: 10.1128/JVI.63.9.3708-3713.1989. View

14.

Gottlinger H, Sodroski J, Haseltine W . Role of capsid precursor processing and myristoylation in morphogenesis and infectivity of human immunodeficiency virus type 1. Proc Natl Acad Sci U S A. 1989; 86(15):5781-5. PMC: 297714. DOI: 10.1073/pnas.86.15.5781. View

15.

Lapatto R, Blundell T, Hemmings A, Overington J, Wilderspin A, Wood S . X-ray analysis of HIV-1 proteinase at 2.7 A resolution confirms structural homology among retroviral enzymes. Nature. 1989; 342(6247):299-302. DOI: 10.1038/342299a0. View

16.

Stevenson M, Haggerty S, Lamonica C, Meier C, Welch S, Wasiak A . Integration is not necessary for expression of human immunodeficiency virus type 1 protein products. J Virol. 1990; 64(5):2421-5. PMC: 249408. DOI: 10.1128/JVI.64.5.2421-2425.1990. View

17.

Weaver T, Talbot K, Panganiban A . Spleen necrosis virus gag polyprotein is necessary for particle assembly and release but not for proteolytic processing. J Virol. 1990; 64(6):2642-52. PMC: 249442. DOI: 10.1128/JVI.64.6.2642-2652.1990. View

18.

Farnet C, Haseltine W . Integration of human immunodeficiency virus type 1 DNA in vitro. Proc Natl Acad Sci U S A. 1990; 87(11):4164-8. PMC: 54068. DOI: 10.1073/pnas.87.11.4164. View

19.

Sherman P, Fyfe J . Human immunodeficiency virus integration protein expressed in Escherichia coli possesses selective DNA cleaving activity. Proc Natl Acad Sci U S A. 1990; 87(13):5119-23. PMC: 54273. DOI: 10.1073/pnas.87.13.5119. View

20.

Craigie R, Fujiwara T, Bushman F . The IN protein of Moloney murine leukemia virus processes the viral DNA ends and accomplishes their integration in vitro. Cell. 1990; 62(4):829-37. DOI: 10.1016/0092-8674(90)90126-y. View