# The role of homologous recombination in human retrovirus-associated diseases

## TL;DR

This review discusses how the RAD51 protein, involved in DNA repair, plays different roles in HIV-1 and HTLV-1 infections, affecting viral persistence and cancer development.

## Contribution

The paper highlights RAD51's dual and contrasting roles in retroviral infections and its potential as a therapeutic target.

## Key findings

- RAD51 is upregulated in HIV-1 to support viral transcription and persistence.
- HTLV-1 suppresses RAD51 to promote error-prone DNA repair and oncogenesis.
- Modulating RAD51 activity could offer new treatments for retrovirus-related cancers.

## Abstract

Human retroviruses such as HIV-1 and HTLV-1 hijack host cellular mechanisms for their replication, survival, and pathogenesis, often causing profound genomic instability. This review explores the dual role of homologous recombination (HR), explicitly mediated by the recombinase RAD51, in the context of retroviral infections. RAD51 is central to high-fidelity repair of DNA double-strand breaks, yet its activity is manipulated differently by HIV-1 and HTLV-1. In HIV-1 infection, RAD51 expression is elevated by viral proteins like Tat and Vpr, promoting DNA repair and enhancing viral transcription through interactions with NF-κB, thereby supporting viral persistence. Conversely, HTLV-1 suppresses RAD51-mediated HR via viral proteins such as p30 and Tax, promoting error-prone DNA repair pathways that contribute to oncogenesis. These contrasting effects may underscore RAD51's functional plasticity as both a facilitator of viral replication and a potential antiviral restriction factor. Furthermore, the therapeutic modulation of RAD51 activity-especially in combination with PARP inhibitors offers promising avenues for treating retrovirus-associated malignancies such as adult T-cell leukemia/lymphoma. This review highlights RAD51 as a pivotal connection in the interplay between genome stability and retroviral pathobiology.