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

Eline Pellaers; Anayat Bhat; Frauke Christ; Zeger Debyser

doi:10.3390/v15010032

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

Viruses. 2022 Dec 21;15(1):32. doi: 10.3390/v15010032.

Authors

Eline Pellaers¹, Anayat Bhat¹, Frauke Christ¹, Zeger Debyser¹

Affiliation

¹ Molecular Virology and Gene Therapy, KU Leuven, Herestraat 49, 3000 Leuven, Belgium.

Abstract

To complete their replication cycle, retroviruses need to integrate a DNA copy of their RNA genome into a host chromosome. Integration site selection is not random and is driven by multiple viral and cellular host factors specific to different classes of retroviruses. Today, overwhelming evidence from cell culture, animal experiments and clinical data suggests that integration sites are important for retroviral replication, oncogenesis and/or latency. In this review, we will summarize the increasing knowledge of the mechanisms underlying the integration site selection of the gammaretrovirus MLV and the lentivirus HIV-1. We will discuss how host factors of the integration site selection of retroviruses may steer the development of safer viral vectors for gene therapy. Next, we will discuss how altering the integration site preference of HIV-1 using small molecules could lead to a cure for HIV-1 infection.

Keywords: HIV-1; MLV; host factors; integration site selection; latency; retroviral integration; viral vector.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Genetic Vectors / genetics
HIV Infections* / therapy
HIV-1* / genetics
Lentivirus / genetics
Retroviridae / genetics
Virus Integration

Grants and funding

This research was funded by the Research Foundation Flanders (FWO) (G0A5316N and SBO–Saphir) and the KU Leuven Research Council (C14/17/095–3M170311).