# Tropism, pathogenicity, and potential for zoonotic spillover of emergent henipa- and henipa-like viruses

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $535,651

## Abstract

ABSTRACT
Nipah (NiV) and Hendra (HeV) viruses are highly pathogenic type species of the Henipavirus (HNV) genus
within the Paramyxovirinae. Zoonotic transmission of NiV and HeV from their natural fruit bat reservoirs to
humans can result in mortality rates in excess of 90%. Originally thought to be limited to Southeast Asia
and Australia, the recent discovery of numerous divergent clades of HNVs across Africa, and of Henipa-like
viruses (HNLV) in China such as the Mojiang paramyxovirus (MojPV), qualitatively changes the risk-
calculus associated with the possible global emergence of these zoonotic viruses. Indeed, we recently
found evidence for HNV spillover into human populations at high-risk for zoonotic transmission in
Cameroon, which raise urgent questions about potential spillover events that may have remained
undetected or misdiagnosed. The recent Ebola epidemic in West Africa underscores the importance of
understanding the mechanisms of zoonotic spillover and transmission of highly pathogenic emerging
viruses. HNVs use EphrinB2 and EphrinB3, highly conserved cellular proteins, as viral entry receptors. The
recent discovery of novel HNVs with differential usage of EphrinB2 and B3 provides new opportunities to
study how receptor usage contributes to the pathogenicity and potential for zoonotic spillover of these
emergent HNVs. Our overall goal is to elucidate the envelope-receptor interactions of HNVs and
HNLVs that contribute to viral tropism, pathogenicity, transmissibility, and the potential for
zoonotic spillover. Our primary objective is to understand the structure-function correlates of envelope-
receptor interactions in the pathobiology of HNV/HNLV zoonotic infections. A secondary objective is to
leverage that understanding to interrogate the rational basis for a vaccine design that might elicit antibodies
that are more broadly neutralizing and effective against an ever-expanding spectrum of diverse HNVs. Our
driving hypothesis is: the structural plasticity of HNV-Gs accounts for the differential efficiency and choice
of receptor usage exhibited by divergent HNVs, and that this contributes to a virulence spectrum among
these zoonotic viruses that is equally diverse. To achieve our objectives and interrogate our driving
hypothesis, we propose the following Specific Aims:
 (1) Investigate the role of receptor usage and choice in virus pathogenicity.
 (2) Evaluate how attachment protein-receptor interactions contribute to transmissibility and the
 potential for zoonotic spillover.
 (3) Examine the implications of the structural and phylogenetic diversity of HNVs on vaccine
design.

## Key facts

- **NIH application ID:** 9989759
- **Project number:** 5R01AI123449-05
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Benhur Lee
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $535,651
- **Award type:** 5
- **Project period:** 2016-09-26 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989759

## Citation

> US National Institutes of Health, RePORTER application 9989759, Tropism, pathogenicity, and potential for zoonotic spillover of emergent henipa- and henipa-like viruses (5R01AI123449-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9989759. Licensed CC0.

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