# Mechanisms of actin cytoskeleton modulation by Pneumoviruses

> **NIH NIH R01** · UNIVERSITY OF KENTUCKY · 2020 · $609,638

## Abstract

The actin cytoskeleton controls key cellular processes, including cell morphology, motility, and intercellular
communication. Many viral pathogens exploit the actin cytoskeletal machinery by a variety of unique
mechanisms to facilitate viral infection, replication, and egress. Currently, the molecular underpinnings of these
viral mechanisms remain poorly defined for a majority of viruses, including members of the Pneumoviridae
family. Human respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are non-segmented
negative strand RNA viruses that are members of the recently created Pneumoviridae family. RSV and HMPV
cause significant disease, including bronchiolitis and lower respiratory tract infection in the pediatric population,
elderly, and immunocompromised individuals. Recent studies from our groups and others have implicated
interactions between actin or actin-interacting proteins and specific pneumovirus proteins in replication and
viral spread; however, the mechanisms and cellular targets required for facilitating actin rearrangements
remain unknown. Our overall hypothesis is that a cascade of specific interactions between pneumovirus
proteins and the actin cytoskeleton regulates key steps in viral infection, including formation of novel
structures critical for virus cell-to-cell spread. Our collaborative team, with expertise in virology, cell
biology, biochemistry, and structural biology, will test our hypothesis through three specific aims. First, we will
dissect the interactions between RSV and HMPV matrix (M) proteins and phosphoproteins (P) that regulate the
actin cytoskeleton within an infected cell. Second, we will determine the biochemical and structural basis for
HMPV phosphoprotein/matrix/actin complex and RSV P/M/actin complex. Finally, we will determine the
mechanisms of intercellular extension formation, stabilization, and utilization in viral spread. At the completion
of these studies, we expect to define molecular mechanisms by which RSV and HMPV interact with and
modulate the host actin cytoskeleton during virus replication, define key elements needed for this modulation,
and understand the molecular details of cell-to-cell spread through intercellular extensions, thus providing
critical new insights that may be applicable in multiple viral systems.

## Key facts

- **NIH application ID:** 9934110
- **Project number:** 5R01AI140758-03
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Rebecca Dutch
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $609,638
- **Award type:** 5
- **Project period:** 2018-06-11 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9934110

## Citation

> US National Institutes of Health, RePORTER application 9934110, Mechanisms of actin cytoskeleton modulation by Pneumoviruses (5R01AI140758-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9934110. Licensed CC0.

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