# Host-virus interactions in hantavirus glycoprotein assembly

> **NIH NIH R56** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2024 · $681,755

## Abstract

PROJECT SUMMARY/ABSTRACT
Rodent-borne orthohantaviruses (hereafter, hantaviruses) are an important group of zoonotic bunyaviruses
associated with over 50,000 annual diagnosed cases of disease worldwide, primarily caused by rodent-to-human
transmission, but also by direct human-to-human contact. Infections by some hantaviruses are associated with
severe disease with up to 40% case-fatality rates. No FDA-approved countermeasures are currently available to
prevent or treat hantavirus infections and disease. Hantaviruses and other members of the order Bunyavirales
(bunyaviruses) encode complex membrane polyproteins that undergo processing and maturation to liberate
virion-incorporated glycoprotein complexes (Gn/Gc). The Gn/Gc complexes mediate viral entry and are the major
targets of the antiviral host antibody response and therapeutic antibodies. Despite their critical roles and the
likelihood that their interactions with host factors provide conserved Achilles’ heels for the development of broadly
acting antivirals, the biogenesis and vesicular trafficking of Gn/Gc complexes remain poorly understood. Here,
we propose to delineate the mechanisms of intracellular assembly, maturation, trafficking, and activity
of glycoprotein complexes from four rodent-infecting hantaviruses representing the Old and New World
clades and causing two distinct human diseases. These complexes are assembled in the ER and then transit
to the Golgi complex, where they are retained to assemble into virions. Our previous studies have identified a)
key mutations in the Old-World Hantaan virus (HTNV) Gn/Gc that relocalize a substantial amount of Gn/Gc to
the plasma membrane, and b) multiple members of the ER membrane complex (EMC) as hits in a haploid genetic
screen for host factors for the New-World Andes virus (ANDV). Using a combination of genetic, virologic, and
mass-spectrometric approaches, our interdisciplinary team plans to identify and define virus-host interactions
required for ER/Golgi retention of Gn/Gc proteins and elucidate the role(s) of the EMC in viral entry and
replication. Our long-term goals are to generate fundamental knowledge about the mechanisms of glycoprotein
biogenesis and function that drive hantavirus infection and create novel avenues for therapeutic intervention
against these agents.

## Key facts

- **NIH application ID:** 11125015
- **Project number:** 1R56AI175292-01A1
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Kartik Chandran
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $681,755
- **Award type:** 1
- **Project period:** 2024-08-07 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11125015

## Citation

> US National Institutes of Health, RePORTER application 11125015, Host-virus interactions in hantavirus glycoprotein assembly (1R56AI175292-01A1). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/11125015. Licensed CC0.

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