Suppressor of Cytokine Signalling 5 (SOCS5) Modulates Inflammatory Responses during Alphavirus Infection

Lukasz Kedzierski; Abigail Er Qi Tan; Isabelle Jia Hui Foo; Sandra E Nicholson; John K Fazakerley

doi:10.3390/v14112476

Suppressor of Cytokine Signalling 5 (SOCS5) Modulates Inflammatory Responses during Alphavirus Infection

Viruses. 2022 Nov 9;14(11):2476. doi: 10.3390/v14112476.

Authors

Lukasz Kedzierski^{1

2}, Abigail Er Qi Tan¹, Isabelle Jia Hui Foo^{1

2}, Sandra E Nicholson^{3

4}, John K Fazakerley^{1

2}

Affiliations

¹ Department of Microbiology and Immunology, at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC 3000, Australia.
² Faculty of Veterinary and Agricultural Sciences, at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC 3000, Australia.
³ Inflammation Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
⁴ Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia.

Abstract

CNS viral infections are one of the major causes of morbidity and mortality worldwide and a significant global public health concern. Uncontrolled inflammation and immune responses in the brain, despite their protective roles, can also be harmful. The suppressor of cytokine signalling (SOCS) proteins is one of the key mechanisms controlling inflammatory and immune responses across all tissues including the brain. SOCS5 is highly expressed in the brain but there is little understanding of its role in the CNS. Using a mouse model of encephalitis, we demonstrate that lack of SOCS5 results in changes in the pathogenesis and clinical outcome of a neurotropic virus infection. Relative to wild-type mice, SOCS5-deficient mice had greater weight loss, dysregulated cytokine production and increased neuroinflammatory infiltrates composed predominantly of CD11b⁺ cells. We conclude that in the brain, SOCS5 is a vital regulator of anti-viral immunity that mediates the critical balance between immunopathology and virus persistence.

Keywords: SOCS; alphavirus; encephalitis.

Publication types

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

MeSH terms

Alphavirus Infections*
Animals
Cytokines* / metabolism
Mice
Signal Transduction
Suppressor of Cytokine Signaling Proteins / genetics

Substances

Cytokines
Suppressor of Cytokine Signaling Proteins
Socs5 protein, mouse

Grants and funding

The work was funded by a University of Melbourne grant to J.K.F.; I.J.H.F. is a recipient of Melbourne Research Scholarship.