# Project-003

> **NIH NIH P01** · UNIVERSITY OF IOWA · 2020 · $340,075

## Abstract

Project Summary/Abstract
Middle East Respiratory Syndrome (MERS) was recognized as a significant illness on
the Saudi Arabian peninsula in mid-2012, and the causative agent was rapidly identified
as a novel coronavirus (CoV), termed MERS-CoV. MERS has a high mortality (~35%),
associated with severe lung disease. Similar to the SARS virus that caused an epidemic
in 2003-4, there is ongoing global concern due to MERS high fatality rate. To date,
cases of MERS have been reported in 26 countries. Dipeptidyl peptidase 4 (DPP4,
CD26) is the receptor for MERS-CoV. Epidemiologic studies have established that
MERS is zoonotic in origin, with evidence for a closely related virus in dromedary camels
on the Arabian peninsula and throughout Africa. Spread from camels to people is
documented, as well as person-to-person spread among health care workers in hospital
settings. A lack of autopsy studies from MERS fatalities has hindered understanding of
MERS-CoV pathogenesis. Thus, MERS is the most recent confirmation that
coronaviruses can jump from their animal hosts, infect humans, and cause severe
disease of global significance. There is a pressing need to better understand MERS
disease pathogenesis and to develop vaccines and therapies. There are 3 specific aims.
Aim 1. To understand how an in vivo evolved MERS-CoV causes lethal lung
disease. We developed mice that have the human receptor for MERS-CoV. Using these
animals we developed a mouse-adapted virus that causes significant lung disease.
These studies will advance our knowledge of the causes of MERS-related lung disease.
Aim 2. To investigate how adaptive mutations in MERS-CoV contribute to
increased virulence. We sequenced the mouse-adapted virus strains and assembled
their genomes. We will use this genetic information to investigate relationships between
the virus gene products and the host responses that lead to severe lung disease.
Aim 3. To investigate how DPP4 abundance and function influence MERS disease
pathogenesis. DPP4 has enzymatic activity that cleaves two amino acids off of target
protein substrates, thereby changing protein functions. DPP4 abundance and enzymatic
activity may contribute to disease. These experiments will advance our knowledge of
how DPP4 activities may underlie to disease outcomes.

## Key facts

- **NIH application ID:** 10229090
- **Project number:** 5P01AI060699-14
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** PAUL B MCCRAY
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $340,075
- **Award type:** 5
- **Project period:** 2004-07-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10229090

## Citation

> US National Institutes of Health, RePORTER application 10229090, Project-003 (5P01AI060699-14). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10229090. Licensed CC0.

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