# Viral and host determinants of susceptibility of diverse hantaviruses

> **NIH NIH R21** · LOUISIANA STATE UNIV HSC SHREVEPORT · 2021 · $165,955

## Abstract

Hantaviruses cause hantavirus cardiopulmonary syndrome (HCPS) and hemorrhagic fever with
renal syndrome (HFRS) with case fatality rates of up to 40% and 14.5%, respectively. FDA-
approved hantavirus drugs and vaccine do not exist. Recent advances in RNA sequencing
technology has led to the discovery of more than 40 genetically distinct hantaviruses carried by
rodents, insectivores (moles and shrews) and bats. Consequently, chances of zoonotic spillover
are likely to be higher in future as deforestation, habitat destruction and climate change will
bring more of the hantavirus reservoir hosts in closer proximity to the human populations.
Despite their huge genetic diversity and public health importance, our understanding of the
molecular determinants of hantavirus susceptibility (capacity for virus entry) and permissivity
(capacity for virus replication) at the cellular level is derived from studies of only a few
hantaviruses and remains rudimentary. This is largely due to the lack of molecular tools and
hantavirus isolates and the general need to study hantaviruses in biosafety level-3 (BSL3)
containment.
Surrogate viruses such as recombinant vesicular stomatitis viruses (rVSVs) pseudotyped with
the hantavirus entry Gn/Gc glycoproteins provide excellent tools for investigating virus entry and
virus-host interactions under BSL-2 containment. Given that the N-terminal domain of Gn (Gn-
NTD) forms most of the surface-exposed part of the Gn/Gc spikes on the virion surface and is
the most divergent region of Gn/Gc, we hypothesize that (i) Gn-NTD diversity is a key viral
determinant of hantavirus susceptibility, and (ii) our recently identified novel hantavirus receptor
PCDH1, a cadherin superfamily member, is required for the entry of at least a subset of novel
hantaviruses. Our primary objective is to generate well-characterized molecular tools to define
viral and host determinants of hantavirus susceptibility and permissivity. In collaboration with
Richard Yanagihara at the University of Hawaii, we will (i) generate rVSVs bearing hantavirus
Gn/Gc glycoproteins representing mammalian hantavirus diversity, (ii) define the candidate
hantavirus receptor requirements for cellular entry of novel hantaviruses, and (iii) finally, we will
apply this knowledge to generate engineered cell lines over-expressing the relevant host factors
for the isolation of authentic non-rodent-borne hantaviruses. These tools will help us achieve our
long-term goals of generating a more comprehensive picture of the viral and host determinants
of hantavirus susceptibility and permissivity at the molecular level.

## Key facts

- **NIH application ID:** 10538154
- **Project number:** 7R21AI156482-02
- **Recipient organization:** LOUISIANA STATE UNIV HSC SHREVEPORT
- **Principal Investigator:** Rohit K Jangra
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $165,955
- **Award type:** 7
- **Project period:** 2021-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10538154

## Citation

> US National Institutes of Health, RePORTER application 10538154, Viral and host determinants of susceptibility of diverse hantaviruses (7R21AI156482-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10538154. Licensed CC0.

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