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

**Authors:** Chulbul M. Ahmed, Rea Dabelic, Simone Kennedy Bedoya, Joseph Larkin, Howard M. Johnson

PMC · DOI: 10.3389/fimmu.2015.00574 · 2015-11-11

## 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.

## Key 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.

## Linked entities

- **Genes:** SOCS1 (suppressor of cytokine signaling 1) [NCBI Gene 8651], SOCS3 (suppressor of cytokine signaling 3) [NCBI Gene 9021], JAK2 (Janus kinase 2) [NCBI Gene 3717], M(2)31A (Minute (2) 31A) [NCBI Gene 44294]
- **Proteins:** SOCS1 (suppressor of cytokine signaling 1), SOCS3 (suppressor of cytokine signaling 3), JAK2 (Janus kinase 2), M(2)31A (Minute (2) 31A)

## Full-text entities

- **Genes:** Jak2 (Janus kinase 2) [NCBI Gene 16452] {aka Fd17}, PTPRC (protein tyrosine phosphatase receptor type C) [NCBI Gene 5788] {aka B220, CD45, CD45R, GP180, IMD105, L-CA}, SOCS1 (suppressor of cytokine signaling 1) [NCBI Gene 8651] {aka AISIMD, CIS1, CISH1, JAB, SOCS-1, SSI-1}, Socs7 (suppressor of cytokine signaling 7) [NCBI Gene 192157] {aka 2310063P06Rik, Nap4}, IFNA1 (interferon alpha 1) [NCBI Gene 3439] {aka IFL, IFN, IFN-ALPHA, IFN-alphaD, IFNA13, IFNA@}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4}, JAK2 (Janus kinase 2) [NCBI Gene 3717] {aka JTK10}, Ifnb1 (interferon beta 1, fibroblast) [NCBI Gene 15977] {aka IFN-beta, IFNB, If1da1, Ifb}, Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, SOCS3 (suppressor of cytokine signaling 3) [NCBI Gene 9021] {aka ATOD4, CIS3, Cish3, SOCS-3, SSI-3, SSI3}, NEU1 (neuraminidase 1) [NCBI Gene 4758] {aka NANH, NEU, SIAL1}, Socs3 (suppressor of cytokine signaling 3) [NCBI Gene 12702] {aka Cis3, Cish3, EF-10, Ef10, SSI-3, Ssi3}, Socs1 (suppressor of cytokine signaling 1) [NCBI Gene 12703] {aka Cish1, Cish7, JAB, SOCS-1, SSI-1}, Cish (cytokine inducible SH2-containing protein) [NCBI Gene 12700] {aka CIS-1, CIS1, Cis, F17, F23, SOCS}, Stat3 (signal transducer and activator of transcription 3) [NCBI Gene 20848] {aka 1110034C02Rik, Aprf}, IFNAR1 (interferon alpha and beta receptor subunit 1) [NCBI Gene 3454] {aka AVP, CRF2-1, IFN-R-1, IFN-alpha-REC, IFNAR, IFNBR}, Ptprc (protein tyrosine phosphatase receptor type C) [NCBI Gene 19264] {aka B220, CD45R, Cd45, L-CA, Ly-5, Lyt-4}, SOCS1/3 [NCBI Gene 12703;12702], Igh-V7183 (immunoglobulin heavy chain (V7183 family)) [NCBI Gene 16059] {aka B9-scFv, IgG, IgH, IgVH1(VSG), VH7183, VI24H}, CISH (cytokine inducible SH2 containing protein) [NCBI Gene 1154] {aka BACTS2, CIS, CIS-1, G18, SOCS}, Gast (gastrin) [NCBI Gene 14459] {aka GAS}, Itgam (integrin alpha M) [NCBI Gene 16409] {aka CD11b/CD18, CR3, CR3A, Cd11b, F730045J24Rik, Ly-40}
- **Diseases:** gastrointestinal (MESH:D005767), Infection (MESH:D007239), lethargic (MESH:D004674), death (MESH:D003643), inflammatory (MESH:D007249), gastric cancer (MESH:D013274), lethargy (MESH:D053609), influenza (MESH:D007251), infectious diseases (MESH:D003141), encephalomyocarditis virus infection (MESH:D014777), cancer (MESH:D009369), neuropsychiatric effects (MESH:D065606), loss of weight (MESH:D015431)
- **Chemicals:** HCl (MESH:D006851), AF-647 (MESH:C569686), DMEM (-), PBS (MESH:D007854), DMSO (MESH:D004121), Tween 20 (MESH:D011136), Tamiflu (MESH:D053139), Alanine (MESH:D000409), crystal violet (MESH:D005840), OPD (MESH:C034193), FC (MESH:C095424), Palmitate (MESH:D010168)
- **Species:** Orthopoxvirus vaccinia (species) [taxon 10245], Mus musculus (house mouse, species) [taxon 10090], Ebola virus [taxon 186536], Influenza A virus (no rank) [taxon 11320], Encephalomyocarditis virus (no rank) [taxon 12104], Homo sapiens (human, species) [taxon 9606], Human alphaherpesvirus 1 (Herpes simplex virus type 1, no rank) [taxon 10298], Dengue virus (no rank) [taxon 12637], H1N1 subtype (serotype) [taxon 114727], West Nile virus (no rank) [taxon 11082]
- **Cell lines:** C57BL/6 — Mus musculus (Mouse), Transformed cell line (CVCL_C0MU), MDCK — Canis lupus familiaris (Dog), Spontaneously immortalized cell line (CVCL_0422), HEK293 — Homo sapiens (Human), Transformed cell line (CVCL_0045)

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC4641302/full.md

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Source: https://tomesphere.com/paper/PMC4641302