# Host factor contribution to positive-strand RNA virus induced membrane reorganization

> **NIH NIH R01** · EMORY UNIVERSITY · 2024 · $487,184

## Abstract

Positive-sense single-strand RNA viruses [(+)RNA viruses] are responsible for a significant portion of human
infections and represent a high risk for new and emerging human diseases. This group of viruses includes
flaviviruses such as dengue virus (DENV), Zika virus (ZIKV), and West Nile Virus (WNV), which are collectively
responsible for >400 million human infections each year. Changes in human population distribution and climate
change that drive movement of insect populations that mediate spread of flaviviruses into new environments
increase the risk of widespread infections in naïve populations. This risk is exemplified by the 2016 outbreak of
Zika virus in South America and is enhanced by the current lack of effective vaccines or antivirals. Studies aimed
at determining the mechanisms of virus infection and interactions between viruses and host cells are vital to
understanding and controlling these pathogens.
The objectives of this study are to interrogate the mechanisms by which flaviviruses utilize host protein
networks that facilitate viral replication and to investigate methods to disrupt these processes. All studied
(+)RNA viruses replicate in host membranes with the majority requiring the ER for the formation of their viral
replication organelles (vROs) that have a high level of morphological conservation between distantly related
(+)RNA virus species. Despite widespread infection, relatively little is known about the specific contribution of
host proteins to the formation or structure of (+)RNA virus vROs. Our preliminary experiments have identified
a network of host membrane factors that are critical to DENV and ZIKV replication, likely having a role in the
formation of vROs. In our first aim, we will define the role of these host membrane proteins in the formation
of vROs for two closely related flaviviruses, DENV and ZIKV. To determine if these host proteins are directly
involved in vRO biogenesis, we will employ unique virus expression and infection systems, which allow
precise evaluation of each step in the virus replication cycle, in combination with integrated microscopy and
biochemical approaches. We will also expand our analysis to determine if the identified host factors have
common functions for other (+)RNA viruses. In our second aim, we will use gene manipulation and
mutagenesis to mechanistically interrogate the function of specific host membrane factors in virus replication
and vRO formation.
 This work will significantly advance understanding of the mechanisms underpinning flavivirus
manipulation of ER membranes, furnishing novel insights into fundamental viral processes likely to be
shared by a broad range of (+)RNA viruses.

## Key facts

- **NIH application ID:** 10973105
- **Project number:** 1R01AI185849-01
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Christopher Neufeldt
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $487,184
- **Award type:** 1
- **Project period:** 2024-06-11 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10973105

## Citation

> US National Institutes of Health, RePORTER application 10973105, Host factor contribution to positive-strand RNA virus induced membrane reorganization (1R01AI185849-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10973105. Licensed CC0.

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