A SOCS1/3 Antagonist Peptide Protects Mice Against Lethal Infection with Influenza A Virus

TL;DR

A new peptide that blocks SOCS1 and SOCS3 proteins protects mice from deadly influenza infections and boosts immune responses.

Contribution

A novel SOCS1/3 antagonist peptide was developed that protects against lethal influenza and enhances immune responses to a universal vaccine antigen.

Findings

The SOCS antagonist protected mice from lethal influenza A virus infection.

The peptide prevented weight loss and temperature drop in infected mice.

It enhanced both cellular and humoral immune responses to the M2e antigen.

Abstract

We have developed an antagonist to suppressor of cytokine signaling 1 (SOCS1), pJAK2(1001–1013), which corresponds to the activation loop of the Janus kinase JAK2, which is the binding site for the kinase inhibitory region (KIR) of SOCS1. Internalized pJAK2(1001–1013) inhibits SOCS1 and SOCS3. SOCS1 has been shown to be an influenza virus-induced virulence factor that enhances infection of cells. The antagonist was protective in cell culture and in influenza virus PR8 lethally infected C57BL/6 mice. The SOCS antagonist also prevented adverse morbidity as assessed by parameters, such as weight loss and drop in body temperature, and showed potent induction of both the cellular and humoral immune responses to the influenza virus candidate universal antigen matrix protein 2 (M2e). The SOCS antagonist, thus, protected mice against lethal influenza virus infection and possessed potent adjuvancy against the M2e candidate influenza virus universal vaccine antigen.

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