SUMOylation and Viral Infections of the Brain

Overview

Journal Pathogens

Date 2022 Jul 27

PMID 35890062

Authors

Fergan Imbert

Gabrielle Leavitt

Dianne Langford

Affiliations

Soon will be listed here.

Abstract

The small ubiquitin-like modifier (SUMO) system regulates numerous biological processes, including protein localization, stability and/or activity, transcription, and DNA repair. SUMO also plays critical roles in innate immunity and antiviral defense by mediating interferon (IFN) synthesis and signaling, as well as the expression and function of IFN-stimulated gene products. Viruses including human immunodeficiency virus-1, Zika virus, herpesviruses, and coronaviruses have evolved to exploit the host SUMOylation system to counteract the antiviral activities of SUMO proteins and to modify their own proteins for viral persistence and pathogenesis. Understanding the exploitation of SUMO is necessary for the development of effective antiviral therapies. This review summarizes the interplay between viruses and the host SUMOylation system, with a special emphasis on viruses with neuro-invasive properties that have pathogenic consequences on the central nervous system.

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References

Marban C, Redel L, Suzanne S, Van Lint C, Lecestre D, Chasserot-Golaz S . COUP-TF interacting protein 2 represses the initial phase of HIV-1 gene transcription in human microglial cells. Nucleic Acids Res. 2005; 33(7):2318-31. PMC: 1084325. DOI: 10.1093/nar/gki529. View

Moore J, June C . Cytokine release syndrome in severe COVID-19. Science. 2020; 368(6490):473-474. DOI: 10.1126/science.abb8925. View

Clement C, Tiwari V, Scanlan P, Valyi-Nagy T, Yue B, Shukla D . A novel role for phagocytosis-like uptake in herpes simplex virus entry. J Cell Biol. 2006; 174(7):1009-21. PMC: 2064392. DOI: 10.1083/jcb.200509155. View

Lokensgard J, Cheeran M, Gekker G, Hu S, Chao C, Peterson P . Human cytomegalovirus replication and modulation of apoptosis in astrocytes. J Hum Virol. 1999; 2(2):91-101. View

Colombo R, Boggio R, Seiser C, Draetta G, Chiocca S . The adenovirus protein Gam1 interferes with sumoylation of histone deacetylase 1. EMBO Rep. 2002; 3(11):1062-8. PMC: 1307602. DOI: 10.1093/embo-reports/kvf213. View

Zhou P, Yang X, Wang X, Hu B, Zhang L, Zhang W . A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020; 579(7798):270-273. PMC: 7095418. DOI: 10.1038/s41586-020-2012-7. View

Boggio R, Passafaro A, Chiocca S . Targeting SUMO E1 to ubiquitin ligases: a viral strategy to counteract sumoylation. J Biol Chem. 2007; 282(21):15376-82. DOI: 10.1074/jbc.M700889200. View

Li Y, Bai W, Hashikawa T . The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. J Med Virol. 2020; 92(6):552-555. PMC: 7228394. DOI: 10.1002/jmv.25728. View

Princz A, Tavernarakis N . SUMOylation in Neurodegenerative Diseases. Gerontology. 2019; 66(2):122-130. DOI: 10.1159/000502142. View

10.

Gullo G, Scaglione M, Cucinella G, Riva A, Coldebella D, Cavaliere A . Congenital Zika Syndrome: Genetic Avenues for Diagnosis and Therapy, Possible Management and Long-Term Outcomes. J Clin Med. 2022; 11(5). PMC: 8911172. DOI: 10.3390/jcm11051351. View

11.

Eggers C, Arendt G, Hahn K, Husstedt I, Maschke M, Neuen-Jacob E . HIV-1-associated neurocognitive disorder: epidemiology, pathogenesis, diagnosis, and treatment. J Neurol. 2017; 264(8):1715-1727. PMC: 5533849. DOI: 10.1007/s00415-017-8503-2. View

12.

Ksiazek T, Erdman D, Goldsmith C, Zaki S, Peret T, Emery S . A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med. 2003; 348(20):1953-66. DOI: 10.1056/NEJMoa030781. View

13.

Marban C, Suzanne S, Dequiedt F, de Walque S, Redel L, Van Lint C . Recruitment of chromatin-modifying enzymes by CTIP2 promotes HIV-1 transcriptional silencing. EMBO J. 2007; 26(2):412-23. PMC: 1783449. DOI: 10.1038/sj.emboj.7601516. View

14.

Seeler J, Dejean A . SUMO and the robustness of cancer. Nat Rev Cancer. 2017; 17(3):184-197. DOI: 10.1038/nrc.2016.143. View

15.

Li G, Maric D, Major E, Nath A . Productive HIV infection in astrocytes can be established via a nonclassical mechanism. AIDS. 2020; 34(7):963-978. PMC: 7429268. DOI: 10.1097/QAD.0000000000002512. View

16.

Johnson E . Protein modification by SUMO. Annu Rev Biochem. 2004; 73:355-82. DOI: 10.1146/annurev.biochem.73.011303.074118. View

17.

Marques C, Hu S, Sheng W, Lokensgard J . Microglial cells initiate vigorous yet non-protective immune responses during HSV-1 brain infection. Virus Res. 2006; 121(1):1-10. DOI: 10.1016/j.virusres.2006.03.009. View

18.

Solomos A, Rall G . Get It through Your Thick Head: Emerging Principles in Neuroimmunology and Neurovirology Redefine Central Nervous System "Immune Privilege". ACS Chem Neurosci. 2016; 7(4):435-41. DOI: 10.1021/acschemneuro.5b00336. View

19.

Elshahawi H, Hassan S, Balasubramaniam V . Importance of Zika Virus NS5 Protein for Viral Replication. Pathogens. 2019; 8(4). PMC: 6963216. DOI: 10.3390/pathogens8040169. View

20.

Li M, Xu X, Chang C, Liu Y . TRIM28 functions as the SUMO E3 ligase for PCNA in prevention of transcription induced DNA breaks. Proc Natl Acad Sci U S A. 2020; 117(38):23588-23596. PMC: 7519263. DOI: 10.1073/pnas.2004122117. View