# Investigation of host glycan requirements for the transmission of influenza viruses at the human-animal interface

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2024 · $792,687

## Abstract

Abstract
Influenza A viruses (IAV) pose a constant threat to human health through both seasonal epidemics and
occasional pandemics, which are often caused by transmission of IAV strains from zoonotic reservoirs. With
the exception of bat IAV, all other IAV strains infect host cells by binding to sialic acid on glycoconjugates
(sialoglycans). Various types of cell surface sialoglycans (N-glycans, O-glycans, glycolipids) display significant
diversity in both structure and carbohydrate composition. In addition, the sialoglycan repertoire can vary
between cell types and across different IAV host species. Thus, defining the structural features in sialoglycans
necessary for IAV infection across different host species is critical for our understanding of zoonotic
transmission into humans. Importantly, there are no reliable strategies that can comprehensively assess and
identify zoonotic IAV strains capable of causing human infections. To define the types of sialoglycans that
facilitate IAV infection, we utilized the CRISPR/Cas9 technique and truncated different types of sialoglycans in
a human lung epithelial cell line either individually or in combination, by targeting glycosyltransferases essential
to biosynthesis. Our studies show that sialic acid on N-glycans, O-glycans and glycolipids can independently
serve as a receptor for several IAV strains from both human and zoonotic hosts. Interestingly, truncation of all
three types of glycans significantly decreased the replication of human by not avian IAV strains, demonstrating
that IAV strains from avian hosts are more flexible in their requirement of sialoglycan structures. Here we
propose to utilize the CRISPR/Cas9 technique to define the structural features of sailoglycans necessary for
IAV infection and adaptation across various host species using primary differentiated cells. Importantly, we will
develop a single cell multi-omics platform to reliably identify zoonotic IAV strains with the potential to cause
human infections. These studies will provide significant insights into our understanding of how the sialoglycan
repertoire shapes host adaptation and fitness of IAV strains.

## Key facts

- **NIH application ID:** 10826886
- **Project number:** 1R01AI174584-01A1
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Balaji Manicassamy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $792,687
- **Award type:** 1
- **Project period:** 2024-07-26 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10826886

## Citation

> US National Institutes of Health, RePORTER application 10826886, Investigation of host glycan requirements for the transmission of influenza viruses at the human-animal interface (1R01AI174584-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10826886. Licensed CC0.

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