The cellular SFPQ protein as a positive factor in the HIV-1 integration

• Published in: Biochimie 2024-07, Vol.222, p.9-17
• Main Authors: Kikhai, Тatiana, Agapkina, Yulia, Silkina, Maria, Prikazchikova, Tatiana, Gottikh, Marina
• Format: Article
• Language: English
• Subjects: HEK293 Cells; HIV Integrase - genetics; HIV Integrase - metabolism; HIV-1 - genetics; HIV-1 - metabolism; HIV-1 - physiology; HIV-1 replication; Host proteins; Humans; Integrase; Mutation; Protein Binding; PTB-Associated Splicing Factor - genetics; PTB-Associated Splicing Factor - metabolism; SFPQ/PSF; Virus Integration; Virus Replication
• ISSN: 0300-9084; 1638-6183; 1638-6183
• DOI: 10.1016/j.biochi.2024.02.002

The cellular SFPQ protein is involved in several stages of the HIV-1 life cycle, but the detailed mechanism of its involvement is not yet fully understood. Here, the role of SFPQ in the early stages of HIV-1 replication has been studied. It is found that changes in the intracellular level of SFPQ affect the integration of viral DNA, but not reverse transcription, and SFPQ is a positive factor of integration. A study of the SFPQ interaction with HIV-1 integrase (IN) has revealed two diRGGX1-4 motifs in the N-terminal region of SFPQ, which are involved in IN binding. Substitution of a single amino acid residue in any of these regions led to a decrease in binding efficiency, while mutations in both motifs almost completely disrupted the SFPQ interaction with IN. The effect of the SFPQ mutants with impaired ability to bind IN on viral replication has been analyzed. Unlike the wild-type protein, the SFPQ mutants did not affect viral integration. This confirms that SFPQ influences the integration stage through direct interaction with IN. Our results indicate that the SFPQ/IN complex can be considered as a potential therapeutic target for the development of new inhibitors of HIV replication. •SFPQ protein positively affect HIV-1 integration due to integrase binding.•SFPQ protein interacts with HIV-1 integrase via its N-terminal domain.•Two diRGGX1-4 motifs of SFPQ are involved in integrase binding.