Viral Exploitation of Host SOCS Protein Functions

Abstract

Over the past decade, a family of host proteins known as suppressors of cytokine signaling (SOCS) have emerged as frequent targets of viral exploitation. Under physiologic circumstances, SOCS proteins negatively regulate inflammatory signaling pathways by facilitating ubiquitination and proteosomal degradation of pathway machinery. Their expression is tightly regulated to prevent excessive inflammation while maintaining protective antipathogenic responses. Numerous viruses, however, have developed mechanisms to induce robust host SOCS protein expression following infection, essentially "hijacking" SOCS function to promote virus survival. To date, SOCS proteins have been shown to inhibit protective antiviral signaling pathways, allowing viruses to evade the host immune response, and to ubiquitinate viral proteins, facilitating intracellular viral trafficking and progeny virus assembly. Importantly, manipulation of SOCS proteins not only facilitates progression of the viral life cycle but also powerfully shapes the presentation of viral disease. SOCS proteins can define host susceptibility to infection, contribute to peripheral disease manifestations such as immune dysfunction and cancer, and even modify the efficacy of therapeutic interventions. Looking toward the future, it is clear that a better understanding of the role of SOCS proteins in viral diseases will be essential in our struggle to modulate and even eliminate the pathogenic effects of viruses on the host.

Suppressor of Cytokine Signaling 1 DNA Administration Inhibits Inflammatory and Pathogenic Responses in Autoimmune Myocarditis

“…Recent studies have indicated that various microbes use the host's SOCS proteins for manipulating cytokine receptor signaling as one of the strategies to evade immune responses (35,36). Coxsackievirus usually infects cardiomyocytes and induces the expression of SOCS1 and SOCS3 in cardiomyocytes, which can result in evasion of immune responses and facilitation of virus replication by inhibition of JAK-STAT signaling (32,37).…”

Building and remodelling Cullin–RING E3 ubiquitin ligases

“…The development of MLN4924, a first-inclass small-molecule inhibitor of NAE that prevents neddylation and, therefore, activation of CRLs could be a useful treatment of non-Hodgkin lymphoma or elapsed and/or refractory multiple myeloma [14,51,116]. CRLs are also hijacked by viruses, including adenovirus, paramyxovirus and HIV [117,118]. In this regard, the inhibition of the neddylation pathway also holds promise as a novel antiretroviral therapeutic to combat HIV [52].…”

SOCS1/3 Expression Levels in HSV-1-Infected, Cytokine-Polarized and -Unpolarized Macrophages

“…Suppressor of cytokine signaling (SOCS) proteins are frequently manipulated by viruses to maintain an infection within the host (Akhtar and Benveniste 2011). The different SOCS proteins inhibit the cytokine-signaling pathway, thereby influencing the inflammatory response (Akhtar and Benveniste 2011).…”