# The biology of the nuclear export protein in influenza A virus replication

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $422,395

## Abstract

PROJECT SUMMARY
In our continued efforts to understand the biology of Influenza A virus (IAV), we have characterized RNA from
both the host and virus using next generation sequencing. These efforts led to the discovery of a small virus-
derived RNA (svRNA) that was necessary for mediating the viral switch from transcription to replication. Upon
characterizing the biology of svRNA, we documented the surprising finding that svRNA synthesis was
dependent on the expression of NEP, a minor protein of the virus that slowly accumulates in the cell as a result
of inefficient splicing. Together, these two discoveries suggested NEP may be the master regulator of IAV
infection. In short, we found that the slow accumulation of NEP provided the virus with a “timer” to coordinate
svRNA production and the subsequent switch from transcription to replication. Furthermore, we, and others,
have found that NEP-mediated svRNA synthesis is dependent on its capacity to induce cRNA. Despite
determining this function for NEP, how it coordinates this activity remains entirely unknown. Here we seek to
understand this activity through three complementary aims. Aim 1 details a strategy to ascertain how NEP
interaction with the RNA dependent RNA polymerase influences its activity. Aim 2 seeks to ascertain why NEP
is associating with host factors involved in RNA processing. Aim 3 investigates the impact of NEP and its
associated proteins on virus pathogenicity and tropism. The experimental strategy comprising these aims will
reveal exciting new molecular targets that can be exploited to generate a novel class of antivirals and will
significantly increase our understanding of IAV replication.

## Key facts

- **NIH application ID:** 9975684
- **Project number:** 5R01AI123155-04
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Benjamin R. tenOever
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $422,395
- **Award type:** 5
- **Project period:** 2017-08-08 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9975684

## Citation

> US National Institutes of Health, RePORTER application 9975684, The biology of the nuclear export protein in influenza A virus replication (5R01AI123155-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9975684. Licensed CC0.

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