# The role of Bik in the replication and severity of influenza A virus

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $462,696

## Abstract

Influenza A virus (IAV) is responsible for seasonal epidemics that results in severe respiratory illness and deaths
worldwide, costing billions of dollars annually in the U.S. alone. Cancer patients are at increased risk of
developing a secondary pneumonia after influenza, which can lead to significant complications. Influenza
infections pose serious challenges due to the lack of effective therapeutic interventions, frequent appearances
of new strains of the virus, and rapid development of drug resistance. New approaches to control infection may
stem from cellular factors or pathways that directly or indirectly interact with viral proteins to enhance or inhibit
virus replication. One of the emerging concepts in the field of IAV is that host cellular factors and pathways are
required for maintaining IAV genome integrity, which is essential for viral replication. Our preliminary data show
that a deficiency of a host cellular protein, Bik, is associated with significant reduction in IAV replication. Our
major findings found that Bik deficiency reduces viral protein levels and viral replication in infected airway
epithelial cells. Furthermore, bik-/- compared to bik+/+ mice exhibit less severe lung inflammation, reduced lung
viral load, and a significant increase in survival rate after infection with IAV. Similarly, a single nucleotide
polymorphism (SNP) in the BIK gene (G→A) that increases Bik expression levels significantly increases viral NP
level and replication in primary normal human bronchial epithelial cells (NHBEs). Furthermore, data from an IAV-
infected human cohort showed that the AA variant of BIK SNP is a risk allele associated with influenza disease
severity. Bik disrupts the interaction of Bcl-2 with IAV-encoded nucleoprotein (NP) and form a Bik/NP complex
that may help assemble viral proteins. The goals of this proposal are to define the role of a host cell protein Bik
in promoting viral replication. Our central hypothesis is that IAV increases host cell Bik protein expression, which
interacts with and disrupts Bcl-2/NP interaction to allow NP to assemble components of viral ribonucleoprotein
(vRNP) and facilitate efficient viral replication. To test this hypothesis, we propose two Specific Aims. Aim 1
identifies the Bik-binding domain of viral NP required for IAV replication. Aim 2 determines whether a
BIK SNP associated with increased Bik expression is a risk factor for influenza disease severity in
humans. Studies are designed to identify the sites of Bik/NP interaction that may serve as potential drug targets
in the future. This study may identify underlying host genetic risk factors contributing to influenza susceptibility
and severity and may have potential implications in regard to targeted prevention and treatment based on
susceptibility factors.
The proposed studies will have significant impacts on the field by dissecting key mechanisms that promote IAV
replication. In the long term, developing peptides or small molecules th...

## Key facts

- **NIH application ID:** 10121522
- **Project number:** 1R01AI148180-01A1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Yohannes Afework Mebratu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $462,696
- **Award type:** 1
- **Project period:** 2021-01-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10121522

## Citation

> US National Institutes of Health, RePORTER application 10121522, The role of Bik in the replication and severity of influenza A virus (1R01AI148180-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10121522. Licensed CC0.

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