Integrase Mutants of Human Immunodeficiency Virus Type 1 with a Specific Defect in Integration

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 1994 Dec 1

PMID 7966634

Citations 35

Authors

B Taddeo

W A Haseltine

C M Farnet

Affiliations

Soon will be listed here.

Abstract

A previous genetic analysis of the human immunodeficiency virus type 1 integrase protein failed to identify single amino acid substitutions that only block the integration of viral DNA (C.-G. Shin, B. Taddeo, W.A. Haseltine, and C.M. Farnet, J. Virol. 68:1633-1642, 1994). Additional substitutions of amino acids that are highly conserved among retroviral integrases were constructed in human immunodeficiency virus type 1 and analyzed for their effects on viral protein synthesis and processing, virion morphology, and viral DNA synthesis and integration in an attempt to identify mutants with a specific defect in integration. Four single amino acid substitutions resulted in replication defective viruses. Conservative, single amino acid substitutions of the two invariant aspartic acid residues found in all retroviral integrases prevented the integration of viral DNA and had no detectable effect on the other stages in the viral replication cycle, indicating that these mutants exhibited a specific defect in integration. Mutations at two positions, S-81 and P-109, blocked the integration of viral DNA but also resulted in the production of viral particles that exhibited reduced reverse transcriptase activity, suggesting additional defects in viral replication. Substitution of the highly conserved amino acid T66 had no effect on viral replication in a CD4+ human T-cell line. This analysis extends the range of possible phenotypes that may be produced by single amino acid substitutions in conserved residues of the integrase protein.

Citing Articles

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.

Engelman A, Kvaratskhelia M Viruses. 2022; 14(5).

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Multivalent interactions essential for lentiviral integrase function.

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Prestimulation of CD2 confers resistance to HIV-1 latent infection in blood resting CD4 T cells.

He S, Guo J, Fu Y, Spear M, Qin C, Fu S iScience. 2021; 24(11):103305.

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Integrase-RNA interactions underscore the critical role of integrase in HIV-1 virion morphogenesis.

Elliott J, Eschbach J, Koneru P, Li W, Puray-Chavez M, Townsend D Elife. 2020; 9.

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