New cellular partners of HIV-1 integrase and their role in viral replication

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Cellular proteins, partners of viral enzymes, are involved in the replication of the human immunodeficiency virus type I (HIV-1) at various stages. Thus, the viral enzyme integrase, participating in several stages of the viral cycle, interacts with various cellular proteins. A number of them are already known, and for some the mechanism of action has been established, but the search for integrase cellular partners continues. In this work, the identification of cellular partners of HIV-1 integrase has been carried out by the cross-linking method followed by mass spectrometry (XL-MS). Twelve new potential integrase partners have been identified, and some of them have been examined for their effect on the early stages of HIV-1 replication.

Full Text

Restricted Access

About the authors

Y. Y. Agapkina

Lomonosov Moscow State University; Lomonosov Moscow State University

Author for correspondence.
Email: agapkina@belozersky.msu.ru

Department of Chemistry, A.N. Belozersky Research Institute of Physico-Chemical Biology

Russian Federation, Moscow; Moscow

T. Y. Ponomareva

Lomonosov Moscow State University

Email: agapkina@belozersky.msu.ru

A.N. Belozersky Research Institute of Physico-Chemical Biology

Russian Federation, Moscow

M. V. Vdovina

Lomonosov Moscow State University

Email: agapkina@belozersky.msu.ru

Department of Chemistry

Russian Federation, Moscow

R. H. Ziganshin

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry

Email: agapkina@belozersky.msu.ru
Russian Federation, Moscow

A. A. Rozina

Lomonosov Moscow State University

Email: agapkina@belozersky.msu.ru

A.N. Belozersky Research Institute of Physico-Chemical Biology

Russian Federation, Moscow

A. N. Anisenko

Lomonosov Moscow State University; Lomonosov Moscow State University

Email: agapkina@belozersky.msu.ru

Department of Chemistry, A.N. Belozersky Research Institute of Physico-Chemical Biology

Russian Federation, Moscow; Moscow

M. B. Gottikh

Lomonosov Moscow State University; Lomonosov Moscow State University

Email: agapkina@belozersky.msu.ru

Department of Chemistry, A.N. Belozersky Research Institute of Physico-Chemical Biology

Russian Federation, Moscow; Moscow

References

  1. Fauci A.S. HIV and AIDS: 20 years of science // Nat Med. 2003. V. 9. № 7. P. 839–843.
  2. Lingappa J.R., Lingappa V.R., Reed J.C. Addressing Antiretroviral Drug Resistance with Host-Targeting Drugs-First Steps towards Developing a Host-Targeting HIV-1 Assembly Inhibitor // Viruses. 2021. V. 13. № 3. P. 451.
  3. Jäger S., Cimermancic P., Gulbahce N., et al. Global landscape of HIV-human protein complexes // Nature. 2011. V. 481. № 7381. P. 365–370.
  4. Schynkel T., Snippenberg W.V., Verniers K., et al. Interactome of the HIV-1 proteome and human host RNA // EMBO ReP. 2024. V. 25. P. 4078–4090.
  5. Delelis O., Carayon K., Saïb A., et al. Integrase and integration: biochemical activities of HIV-1 integrase // Retrovirology. 2008. V. 5. P. 114.
  6. Engelman A.N. and Maertens G.N. Retrovirus-Cell Interactions. Academic Press, San Diego, CA, P. 163–198. 2018.
  7. Rozina A., Anisenko A., Kikhai T., et al. Сomplex Relationships between HIV-1 Integrase and Its Cellular Partners // Int. J. Mol. Sci. 2022. V. 23. P. 12341.
  8. Engelman A.N. and Kvaratskhelia M. Multimodal Functionalities of HIV-1 Integrase // Viruses. 2022. V. 14. P. 926.
  9. Ciuffi A., Llano M., Poeschla E., et al. A role for LEDGF/p75 in targeting HIV DNA integration // Nat Med. 2005. V. 11. P. 1287–1289.
  10. Yamamoto S.P., Okawa K., Nakano T., et al. Huwe1, a novel cellular interactor of Gag-Pol through integrase binding, negatively influences HIV-1 infectivity // Microbes Infect. 2011. V. 13. № 4. P. 339–349.
  11. Allouch A., Di Primio C., Alpi E., et al. The TRIM family protein KAP1 inhibits HIV-1 integration // Cell Host Microbe. 2011. V. 9. P. 484–495.
  12. Ait-Ammar A., Bellefroid M., Daouad F., et al. Inhibition of HIV-1 gene transcription by KAP1 in myeloid lineage // Sci ReP. 2021. V. 11. P. 2692.
  13. Hearps A.C., Jans D.A. HIV-1 integrase is capable of targeting DNA to the nucleus via an Importin α/β-dependent mechanism // Biochemical Journal. 2006. V. 398. № 3. P. 475–484. doi: 10.1042/bj20060466
  14. Dziuba N., Ferguson M.R., O’Brien W.A., et al. Identification of cellular proteins required for replication of human immunodeficiency virus type 1 // AIDS Res Hum Retroviruses. 2012. V. 28. P. 1329–1339.
  15. Yoder A., Yu D., Dong L., et al. HIV envelope-CXCR4 signaling activates cofilin to overcome cortical actin restriction in resting CD4 T cells // Cell. 2008. V. 134. P. 782–792.
  16. Speth C., Prohászka Z., Mair M., et al. A 60 kD heat-shock protein-like molecule interacts with the HIV transmembrane glycoprotein gp41 // Mol Immunol. 1999. V. 36. № 9. P. 619–628.
  17. Ha H.C., Juluri K., Zhou Y., et al. Poly(ADP-ribose) polymerase-1 is required for efficient HIV-1 integration // Proc Natl Acad Sci USA. 2001. V. 98. P. 3364–3368.
  18. Bueno M.T., Reyes D., Valdes L., et al. Poly(ADP-ribose) polymerase 1 promotes transcriptional repression of integrated retroviruses // J Virol. 2013. V. 87. № 5. P. 2496–2507.
  19. Ramakrishnan R., Liu H., Donahue H., et al. Identification of novel CDK9 and Cyclin T1-associated protein complexes (CCAPs) whose siRNA depletion enhances HIV-1 Tat function // Retrovirology. 2012. V. 9. P. 90.
  20. Knyazhanskaya E., Anisenko A., Shadrina O., et al. NHEJ pathway is involved in post-integrational DNA repair due to Ku70 binding to HIV-1 integrase // Retrovirology. 2019. V. 16. № 1. P. 30.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. Effect of changing the intracellular concentration of DnaJA1, Cofilin 1, 14-3-3ξ/δ, and CacyBP proteins on the efficiency of cell transduction with HIV-1-based lentiviral vector. A. Western blot analysis results for protein overexpression. Visualization with antibodies to 3xFLAG and actin. B. Relative mRNA level of proteins after knockdown with siRNA. C. Relative luminescence level for protein overexpression. D. Relative luminescence level for protein knockdown. p-values ​​were calculated using the Mann–Whitney U test. * p-value <0.05, ** p-value <0.01, *** p-value <0.001, **** p-value <0.0001.

Download (556KB)
Indexing metadata

Note

Presented by Academician of the RAS O.A. Dontsova


Copyright (c) 2025 Russian Academy of Sciences