# Origin of the innate immunity suppression caused by nairovirus' protease activity

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA RIVERSIDE · 2024 · $75,608

## Abstract

Summary/Abstract
Crimean-Congo hemorrhagic fever virus (CCHFV) is a ssRNA (-) nairovirus that produces fever,
prostration, and severe hemorrhages in humans. Fatality rates associated with CCHFV range from 5-
80% based on phylogenetic variation of the virus, transmission route, and different treatment facilities.
Originally identified in Russia and the Congo, CCHFV has rapidly spread across large sections of
Europe, Asia, and Africa. Recently, CCHFV has illustrated its continued ability to spread into
previously naive regions. At the same time, U.S. citizen traffic has increased substantially to the
regions endemic with CCHFV, specifically South-Central Asia. As a result, there is a substantial risk
for transmission of CCHFV and/or its tick vector to the United States. Intriguingly, CCHFV is not the
only nairovirus that threatens the public. Nairobi Sheep Disease virus (NSDV) as well as nairoviruses
Issyk-kul, Dugbe and Erve can cause human disease of varying severity and economic distress. There
is no vaccine or prophylactic currently available for treatment of CCHF or any other nairovirus related
disease. Reports have identified a viral homologue of the ovarian tumor protease (vOTU) located
within the nairovirus genome. Recently, vOTUs’ ability to reverse post-translational modification by
proteins ubiquitin (Ub) and Ub-like interferon-simulated gene 15 (ISG15) on a narrow subset of host
pathways has been illustrated to be critical to pathogenesis. Also, vOTUs from CCHFV and other
nairoviruses have been found to be sensitive to species-species variations in ISG15 and their
specificity includes at least the species that disease is most prominently identified. This proposal will
determine the identity of specific host proteins within those pathways targeted by vOTUs. This will
enable therapeutic approaches that protect, or elevate, specific host inhibitory factors for these
viruses. The proposal will also seek to evaluate the correlation between the in vitro activity/substrate
species-specificity of these nairovirus vOTUs and overall virulence and zoonotic range of the
nairoviruses in question. Additionally, the efficacy of using CCHFV vaccine candidates with altered
CCHF vOTU functions will be assessed. Together, the resulting information will provide critical insight
into the role of vOTUs play in pathogenesis and host restriction as well as advance the development
of prophylactics targeting vOTUs.

## Key facts

- **NIH application ID:** 10898165
- **Project number:** 3R01AI151006-05S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA RIVERSIDE
- **Principal Investigator:** Scott Dusan Pegan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $75,608
- **Award type:** 3
- **Project period:** 2020-09-16 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10898165

## Citation

> US National Institutes of Health, RePORTER application 10898165, Origin of the innate immunity suppression caused by nairovirus' protease activity (3R01AI151006-05S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10898165. Licensed CC0.

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