# Structural Studies of Rotaviruses

> **NIH NIH R37** · BAYLOR COLLEGE OF MEDICINE · 2020 · $665,150

## Abstract

The long-term goal of our research is to understand the structural basis of the complex processes that regulate
the replication cycle of rotaviruses (RVs), which are the global pathogens causing life-threatening infantile
gastroenteritis. During 2013-2016, our studies have answered several questions we previously asked, raised
a new set of questions, and revealed novel concepts. As a result, we plan to pursue exciting new directions
during the MERIT extension period (2018-2023) through four new AIMS. In pursuing these AIMs, we will use
a multipronged approach involving glycan array screening, X-ray crystallography, single-particle cryo-EM,
cryo-electron tomography of RV-infected cells, and functional assays. In AIM1, considering that specific
recognition of host cell glycans is a critical factor in host cell attachment and cross-species transmission, we
will address new questions such as: (i) what is the glycan specificity in sialidase-insensitive animal RVs with
zoonotic potential?; (ii) do these viruses show similar correlated glycan specificity with the human RVs we
discovered in bovine and human P[11] RVs to cross the species barrier?; (iii) does glycan binding affect spike
structure in the intact virion to influence downstream cell entry processes?; and (iv) do VP8*-specific human
mAbs block glycan binding in human RVs?. In AIM 2, our goal is to understand the structural aspects of the
viral capping enzyme VP3, how it associates with the viral polymerase VP1 to gain insight into the mechanistic
basis of endogenous transcription, and the possible role of VP3 in capsid assembly and genome encapsidation
that occurs in the specialized replication factories called viroplasms. Experiments in AIM 3 are designed to
probe further into understanding protein-protein interaction networks that regulate viroplasm-associated
activities using structural techniques and cryo-ET of RV-infected cells at different time points post infection. In
AIM 4, our goal is to provide structure-based mechanistic insights into how RVs antagonize cellular antiviral
responses by understanding structural aspects of RV proteins such as NSP1 that inhibit IFN pathways and the
phosphodiesterase domain embedded in VP3 of group-A RVs that inactivates OAS/RNase-L pathway, and
the dsRNA-binding domain in NSP3 of group-C RVs that inhibits dsRNA-dependent protein kinase.

## Key facts

- **NIH application ID:** 9858206
- **Project number:** 5R37AI036040-32
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Bidadi Venkataram Prasad
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $665,150
- **Award type:** 5
- **Project period:** 1988-12-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9858206

## Citation

> US National Institutes of Health, RePORTER application 9858206, Structural Studies of Rotaviruses (5R37AI036040-32). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9858206. Licensed CC0.

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