Host Proteins Interacting with the Moloney Murine Leukemia Virus Integrase: Multiple Transcriptional Regulators and Chromatin Binding Factors

Overview

Journal Retrovirology

Publisher Biomed Central

Specialty Microbiology

Date 2008 Jun 17

PMID 18554410

Citations 45

Authors

Barbara Studamire

Stephen P Goff

Affiliations

Soon will be listed here.

Abstract

Background: A critical step for retroviral replication is the stable integration of the provirus into the genome of its host. The viral integrase protein is key in this essential step of the retroviral life cycle. Although the basic mechanism of integration by mammalian retroviruses has been well characterized, the factors determining how viral integration events are targeted to particular regions of the genome or to regions of a particular DNA structure remain poorly defined. Significant questions remain regarding the influence of host proteins on the selection of target sites, on the repair of integration intermediates, and on the efficiency of integration.

Results: We describe the results of a yeast two-hybrid screen using Moloney murine leukemia virus integrase as bait to screen murine cDNA libraries for host proteins that interact with the integrase. We identified 27 proteins that interacted with different integrase fusion proteins. The identified proteins include chromatin remodeling, DNA repair and transcription factors (13 proteins); translational regulation factors, helicases, splicing factors and other RNA binding proteins (10 proteins); and transporters or miscellaneous factors (4 proteins). We confirmed the interaction of these proteins with integrase by testing them in the context of other yeast strains with GAL4-DNA binding domain-integrase fusions, and by in vitro binding assays between recombinant proteins. Subsequent analyses revealed that a number of the proteins identified as Mo-MLV integrase interactors also interact with HIV-1 integrase both in yeast and in vitro.

Conclusion: We identify several proteins interacting directly with both MoMLV and HIV-1 integrases that may be common to the integration reaction pathways of both viruses. Many of the proteins identified in the screen are logical interaction partners for integrase, and the validity of a number of the interactions are supported by other studies. In addition, we observe that some of the proteins have documented interactions with other viruses, raising the intriguing possibility that there may be common host proteins used by different viruses. We undertook this screen to identify host factors that might affect integration target site selection, and find that our screens have generated a wealth of putative interacting proteins that merit further investigation.

Citing Articles

The Integrase: An Overview of a Key Player Enzyme in the Antiviral Scenario.

Renzi G, Carta F, Supuran C Int J Mol Sci. 2023; 24(15).

PMID: 37569561 PMC: 10419282. DOI: 10.3390/ijms241512187.

Determinants of Retroviral Integration and Implications for Gene Therapeutic MLV-Based Vectors and for a Cure for HIV-1 Infection.

Pellaers E, Bhat A, Christ F, Debyser Z Viruses. 2023; 15(1).

PMID: 36680071 PMC: 9861059. DOI: 10.3390/v15010032.

Complex Relationships between HIV-1 Integrase and Its Cellular Partners.

Rozina A, Anisenko A, Kikhai T, Silkina M, Gottikh M Int J Mol Sci. 2022; 23(20).

PMID: 36293197 PMC: 9603942. DOI: 10.3390/ijms232012341.

BET-Independent Murine Leukemia Virus Integration Is Retargeted and Selects Distinct Genomic Elements for Lymphomagenesis.

Nombela I, Michiels M, Van Looveren D, Marcelis L, El Ashkar S, Van Belle S Microbiol Spectr. 2022; 10(4):e0147822.

PMID: 35852337 PMC: 9431007. DOI: 10.1128/spectrum.01478-22.

Retroviral integrase: Structure, mechanism, and inhibition.

Oliveira Passos D, Li M, Craigie R, Lyumkis D Enzymes. 2021; 50:249-300.

PMID: 34861940 PMC: 8732146. DOI: 10.1016/bs.enz.2021.06.007.

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