# TONSILS: AN UNRECOGNIZED ROLE IN INFLUENZA VIRUS EVOLUTION

> **NIH NIH K99** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2022 · $100,000

## Abstract

Identifying the host factors that contribute to influenza virus (IV) pathogenesis are critical for disease control and preventing
pandemics. The tonsils comprise 2 lymphoid organs located in the nasopharynx of mammals and in the cecum of birds, in
which IVs are enteric. The tonsils are an initial site of various viral infections and transmission, but their role in IV
pathogenesis is unclear. My proposed studies will provide new insights on how the tonsils contribute to IV pathogenesis,
immune responses, and adaptation by identifying the role of the tonsils in IV pathogenesis, performing tonsillectomy in
ferrets to recapitulate the heterogeneous responses to IV infection severity and vaccination in subpopulations of humans
with/without tonsils, and exploring the role of the tonsils in IV adaptation. My recent study demonstrated that human
tonsillar epithelial cells (HTECs) are susceptible to IV infections, with effective replication of different IV subtypes in vitro.
I will expand upon these findings by performing time-intensive monitoring of IV infection dynamics and distribution in the
tonsils of ferrets. I collected and analyzed human tonsillectomy data over the last 60 years in the US and found that the
percentage of human subpopulations with tonsillectomies is high in different age groups. The prevalence, disease severity,
and level of immunity of IV infections in these subpopulations are unknown, and the role of the tonsils in epidemic or
pandemic spread of IVs is undetermined. I previously found that HTECs induce chemokine and cytokine release during IV
infection. Previous clinical studies reported no differences in salivary IgA immune responses to IV live attenuated vaccine
in individuals before and after tonsillectomy, but these studies were limited by low patient numbers and confounded by
original antigenic sin. I will use ferrets to ascertain how tonsillectomy affects immunity resulting from the IV infection and
vaccine. I will measure the quantity and quality of antibody responses after infection and/or immunization and compare T-
cell and B-cell activity in ferrets with and without tonsils. The soft palate is an important site of IV adaptation, extending
downward in the oral cavity and passing anterior and posterior to the tonsils. The replicative fitness of IVs in tonsillar tissues
may induce rapid selection, ostensibly preventing infection and reducing their pandemic potential. Therefore, I propose to
verify the role of the tonsils in IV adaptation a tissue not typically sampled in animal models of IV and investigate the extent
of different human IV replication in the tonsils. Acquiring mutations and switching receptor-binding specificity between
avian and human sialic acid (SA) preferences are key for IV transmission and adaptation. I previously found that both human
and avian tonsil epithelial cells are rich in both human α2,6 and avian α2,3–linked SA receptors and support IV replication.
I will use genetically engineered IVs with...

## Key facts

- **NIH application ID:** 10525875
- **Project number:** 1K99AI166019-01A1
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **Principal Investigator:** Faten Abdelaal Okda
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $100,000
- **Award type:** 1
- **Project period:** 2022-08-04 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10525875

## Citation

> US National Institutes of Health, RePORTER application 10525875, TONSILS: AN UNRECOGNIZED ROLE IN INFLUENZA VIRUS EVOLUTION (1K99AI166019-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10525875. Licensed CC0.

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