# Immunomodulatory effects of coronavirus membrane proteins E, M, and S.

> **NIH NIH R21** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2020 · $420,750

## Abstract

ABSTRACT
COronaVIrus Disease 2019 (COVID-19) is caused by a human coronavirus, SARS-CoV-2. This virus
caused a large outbreak in China that was associated with a high human-to-human transmission rate and mortality
and subsequently led to a pandemic in the human population. SARS-CoV-2 is member of the â-coronaviruses and
is highly related to SARS-CoV. In an ongoing evolutionary arms race, viruses have evolved factors that facilitate
their replication while the host cell has evolved signaling networks to detect and eradicate invading viruses. The
innate immune system is a conserved defense strategy critical for the initial detection and restriction of pathogens
and later activation of the adaptive immune response. Activation of innate immunity relies on the recognition of
pathogen-associated molecular patterns (PAMP) by pattern recognition receptors (PRRs) such as Toll-like
receptors, RNA and DNA sensors. Upon activation by PAMPs, PRRs recruit adaptor proteins that initiate signaling
pathways involving modifying enzymes such as kinases, phosphatases, E3 ubiquitin ligases that ultimately lead
to the activation of crucial transcription factors including IRF3 and NF-êB. Synergistically, these factors promote
the production of antiviral type I interferons (IFN-I), inflammatory cytokines, NK cell immunity, apoptosis, and
autophagy. Thus, the pathogenicity and spread of a virus in the host is in part determined by the ability of the virus
to evade host cell innate responses. The SARS-CoV-2 virion has three transmembrane proteins [envelope (E),
membrane (M), and spike (S)] that are necessary for viral assembly and infectivity. They also have important
immunomodulatory functions as they trigger or antagonize innate immune responses within infected cells. The
E proteins from other coronaviruses have been shown to form an oligomeric structure with ion channel activity that
can alter calcium homeostasis with implications on viral pathogenesis. The M protein of other coronaviruses was
shown to have a range of immunomodulatory effects through TLR-dependent and independent mechanisms and
the S protein can exert its effects by modulating surface signaling responses. It also causes the degradation of
BST-2 (tetherin), which functions to prevent release of progeny virus. We hypothesize that the
immunomodulatory properties of SARS-CoV-2 membrane proteins will determine the outcome of the
infection and viral mediated pathogenesis. To test this, in Aim 1, we propose to examine E, M, and S proteins
from SARS-CoV-2 and compare their impact in modulating innate immunity, proinflammatory responses,
autophagy, and apoptosis with the same proteins from SARS-CoV, MERS-CoV, and HCoV-OC43. In Aim 2, we
will determine the immunomodulatory effects of virus-like particles (VLPs) formed by the membrane proteins of
the four viruses. We will also determine the immunoevasion capabilities of of SARS-CoV-2 and compare them
with SARS-CoV, MERS and HCoV-OC43. Overall, the results of thes...

## Key facts

- **NIH application ID:** 10178404
- **Project number:** 1R21AI158229-01
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** Maria Kalamvoki
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $420,750
- **Award type:** 1
- **Project period:** 2020-08-17 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10178404

## Citation

> US National Institutes of Health, RePORTER application 10178404, Immunomodulatory effects of coronavirus membrane proteins E, M, and S. (1R21AI158229-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10178404. Licensed CC0.

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