# Mechanisms of Intrinsic Host Responses to Hantavirus Infection

> **NIH NIH K22** · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · 2021 · $106,320

## Abstract

The Old World hantaviruses, Hantaan virus (HTNV) and Seoul virus (SEOV), are the etiologic agents of
hemorrhagic fever with renal syndrome (HFRS), the most common hemorrhagic fever disease in Asia, with case
fatality rates up to 15%. Hantaviruses are zoonotic RNA viruses found in insectivore and rodent hosts worldwide.
In their respective reservoir hosts, hantaviruses establish asymptomatic, persistent infections. The mechanisms
underlying these divergent infection outcomes remain unknown and no therapeutic exists to treat HFRS. We
have determined that early antiviral signaling in HTNV infection of murine and human cells requires MAVS, the
signaling adapter protein for cytoplasmic pathogen recognition receptors RIG-I and MDA5. Further, we have
demonstrated that type I interferon signaling is essential for early control of HTNV replication and tissue
dissemination in vivo. Through global transcriptional profiling, we have revealed gene networks responsible for
endothelial homeostasis and inflammation that are differentially regulated during SEOV infection between
reservoir and human endothelial cells. Predicted network analysis identified differential regulation of the vascular
endothelial growth factor (VEGF) receptor signaling pathway, with increased receptor gene expression in human
cells coordinate with increased gene expression related to angiogenesis and migration compared to reservoir
endothelial cells. We hypothesize that virus-host molecular interactions in Old World hantavirus infections
determine innate antiviral responses and drive differential gene expression associated with infection outcome.
We will address this hypothesis by: 1) further defining the virus-host interactions that direct antiviral signaling to
HTNV infection in human endothelial cells, 2) uncovering the mechanism(s) by which SEOV directs endothelial
activation and barrier permeability through differential modulation of VEGF signaling in human and rat endothelial
cells. Our investigations will lead to identification of novel targets for therapeutic intervention and innovative
strategies for vaccine design for HFRS.

## Key facts

- **NIH application ID:** 10107751
- **Project number:** 5K22AI141680-02
- **Recipient organization:** UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
- **Principal Investigator:** Alison Kell
- **Activity code:** K22 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $106,320
- **Award type:** 5
- **Project period:** 2020-02-14 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10107751

## Citation

> US National Institutes of Health, RePORTER application 10107751, Mechanisms of Intrinsic Host Responses to Hantavirus Infection (5K22AI141680-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10107751. Licensed CC0.

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