# Role of host protein GBF1 in organizing enterovirus replication complexes

> **NIH NIH R01** · UNIV OF MARYLAND, COLLEGE PARK · 2020 · $373,750

## Abstract

Description of the project. Viruses are the ultimate intracellular parasites. With minimal genetic
resources they are able to reroute cellular metabolic pathways and hijack cellular proteins to promote
their own replication. Thus, understanding the role of specific host factors in the viral life cycle is essential
for the development of novel anti-viral strategies. Enteroviruses are a group of picornaviruses, small
+RNA viruses of vertebrates including humans. Enteroviruses cause clinically and economically
important human diseases, ranging from the common cold to fatal encephalitis and myocarditis. High
genetic diversity and adaptability of these viruses complicates development of comprehensive vaccines
and traditional therapeutics targeting virus-specific proteins. Of all the pathogenic enteroviruses, only
polioviruses can be controlled with vaccines, and no clinically approved anti-enterovirus drugs are
available. Thus, novel approaches are urgently needed to control enteroviruses associated with human
diseases. Picornaviruses replicate their genomes on specialized membrane domains, replication
organelles that feature unique lipid and protein composition and whose development relies on the re-
organization of cellular lipid synthesis and membrane trafficking pathways. This implies that at least some
cellular membrane metabolism components must be indispensable for viral propagation. Indeed,
enteroviruses universally require the host protein GBF1 for their replication. GBF1 is a large multi-domain
protein that functions as a guanine nucleotide exchange factor (GEF) for select small GTPases of the Arf
family. GBF1 is a master coordinator of the early steps of protein transport in the secretory pathway, and
participates in maintaining Golgi structure and function and in lipid droplet metabolism. However, how
GBF1 supports the viral replication cycle remains unknown. Attempts to relate the known cellular
activities of GBF1 such as Arf activation, membrane remodeling and recruitment of cellular proteins to
membranes to GBF1 function in viral replication produced controversial results. GBF1 is known to interact
with numerous cellular proteins and with the enterovirus replication protein 3A, but how viruses use these
interactions to their advantage remains unknown. Herein, we propose a new model in which GBF1 acts
as a molecular scaffold to coordinate the assembly of viral and cellular proteins into operational replication
complexes. For this project, we built a team of a cell biologist with a superior expertise in GBF1 biology
(Sztul), and a virologist with an outstanding background in picornavirus replication (Belov). Together, we
will delineate the step(s) in viral life cycle that require GBF1 and uncover the mechanisms of GBF1 action
in the formation function of replication complexes. The universal reliance of diverse enteroviruses on
GBF1 provides an unprecedented opportunity for the development of broad-spectrum therapeutics
targeting GBF1-cont...

## Key facts

- **NIH application ID:** 9927989
- **Project number:** 5R01AI125561-05
- **Recipient organization:** UNIV OF MARYLAND, COLLEGE PARK
- **Principal Investigator:** George A. Belov
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $373,750
- **Award type:** 5
- **Project period:** 2016-06-14 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9927989

## Citation

> US National Institutes of Health, RePORTER application 9927989, Role of host protein GBF1 in organizing enterovirus replication complexes (5R01AI125561-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9927989. Licensed CC0.

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