BELOV LABORATORY
Replication of positive-strand RNA viruses and virus-host interaction
ABOUT THE LAB​
Positive strand RNA viruses infect all eukaryotic organisms. These viruses include such important pathogens of humans and animals as hepatitis C virus, Foot and Mouth Disease virus, poliovirus, Dengue viruses, Zika virus, rhinoviruses, and many others. The majority of pathogenic positive-strand RNA viruses still cannot
be controlled with vaccines or antiviral drugs. These viruses usually have small genomes coding for a limited number of proteins, thus they have to rely on simple but efficient strategies of hijacking cellular metabolism and fighting host antiviral defenses. Importantly, even distantly related positive-strand RNA viruses often rely on the same cellular factors and processes for their propagation, thus providing a possibility of developing broad-spectrum anti-viral therapeutics targeting the critical virus-host interactions.
We are particularly interested in Enteroviruses, a group of small positive-strand RNA viruses of the family Picornaviridae. Enteroviruses replicate in the respiratory or alimentary tracts and are arguably the largest group of viruses infecting humans. Enteroviruses also infect multiple animal species including farm animals and thus have the potential for zoonotic transmission.
We employ modern molecular biology and virology techniques to study the mechanisms of these viruses use to hijack and subvert normal cellular pathways for the development of viral replication complexes. The area of our special interest is how these viruses disassemble elements of normal cellular membrane metabolism and then combine them into new configurations to remodel cellular membranes into viral replication organelles.
Understanding these processes will provide us with new and effective measures against those pathogens which are markedly resistant to conventional therapies. Investigation of viral strategies of manipulating host metabolism also elucidates the intricate machinery of cellular regulatory networks which have important implications for broad areas of human and animal health from inflammation to cancer. Another important direction of our research is the development of novel anti-enterovirus vaccines. Enterovirus infections can be associated with multiple pathologies from the trivial common cold to such serious conditions as full or partial paralysis, viral encephalitis, fulminant myocarditis, and others. The long-term complications of enteroviral infections include the development of asthma, type one diabetes, and dilated cardiomyopathy. While the majority of enteroviral infections are mild or symptomatic, they can be particularly dangerous for infants and young children because they lack protective antibodies. The vast antigenic diversity of enteroviruses makes the development of traditional vaccines economically feasible only against a few of them. Among all pathogenic enteroviruses, licensed vaccines are currently available only against poliovirus and enterovirus A71. We develop novel vaccine approaches based on viral vector expression of protective enterovirus antigens, which can be rapidly deployed against any emerging enteroviral threat, as well as vaccine products aimed at inducing the immune responses against conserved replication proteins to provide a broad spectrum of protection against diverse enteroviruses.
DR. GEORGE BELOV
Associate Professor,
Principal Investigator,
Doctor of Philosophy
DR. EKATERINA VIKTOROVA
Assistant Research Professor,
Doctor of Philosophy
ANNA ZIMINA
Bachelor of Science
SAMUEL GABAGLIO
Bachelor of Science
ISHITA ROY CHOWDHURY
Master of Science
MARCOS FLORENTIN
Master of Science
FINN MCGHEE
Undergraduate Intern
Former Members:
MOHAMMAD ELBEHAIRY
Doctor of Philosophy,
Doctor of Veterinary Medicine
SEYEDEHMAHSA MOGHIMI
Doctor of Philosophy,
Doctor of Veterinary Medicine
JULES NCHOUTMBOUBE
Doctor of Philosophy
LAUREN A. FORD-SILTZ
Doctor of Philosophy
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PUBLICATIONS
Zimina A, Viktorova EG, Moghimi S, Nchoutmboube J, Belov GA. Interaction of Poliovirus Capsid Proteins with the Cellular Autophagy Pathway. Viruses. 2021 Aug 11;13(8):1587. doi: 10.3390/v13081587.
Moghimi S, Viktorova E, Zimina A, Szul T, Sztul E, Belov GA. Enterovirus Infection Induces Massive Recruitment of All Isoforms of Small Cellular Arf GTPases to the Replication Organelles.J Virol. 2020 Dec 22;95(2):e01629-20. doi: 10.1128/JVI.01629-20. Print 2020 Dec 22.
Viktorova EG, Gabaglio S, Meissner JM, Lee E, Moghimi S, Sztul E, Belov GA. A redundant mechanism of recruitment underlies the remarkable plasticity of the requirement of poliovirus replication for the cellular ArfGEF GBF1. J Virol. 2019 Aug 2;. doi: 10.1128/JVI.00856-19. [Epub ahead of print] PubMed PMID: 31375590.
Viktorova EG, Nchoutmboube JA, Ford-Siltz LA, Iverson E, Belov GA. Phospholipid synthesis fueled by lipid droplets drives the structural development of poliovirus replication organelles. PLoS Pathog. 2018 Aug 27;14(8):e1007280. doi:10.1371/journal.ppat.1007280. eCollection 2018 Aug. PubMed [citation] PMID:30148882, PMCID: PMC6128640
Viktorova EG, Khattar SK, Kouiavskaia D, Laassri M, Zagorodnyaya T, Dragunsky E, Samal S, Chumakov K, Belov GA. Newcastle Disease Virus-Based Vectored Vaccine against Poliomyelitis. J Virol. 2018 Aug 16;92(17). pii: e00976-18. doi:10.1128/JVI.00976-18. Print 2018 Sep 1. PubMed [citation] PMID: 29925653, PMCID: PMC6096817
Belov GA. Dynamic lipid landscape of picornavirus replication organelles. Curr Opin Virol. 2016 May 27;19:1-6. doi: 10.1016/j.coviro.2016.05.003.
Zhang J, Zhang Z, Chukkapalli V, Nchoutmboube JA, Li J, Randall G, Belov GA, Wang X. Positive-strand RNA viruses stimulate host phosphatidylcholine synthesis at viral replication sites. Proc Natl Acad Sci U S A. 2016 Feb 23;113(8):E1064-73. doi: 10.1073/pnas.1519730113. Epub 2016 Feb 8.
Viktorova EG, Nchoutmboube J, Ford-Siltz LA and Belov GA. Cell-Specific Establishment of Poliovirus Resistance to an Inhibitor Targeting a Cellular Protein. J Virol. 2015 Apr 15;89(8):437286. doi: 10.1128/JVI.00055-15. Epub 2015 Feb 4.
Ilnytska O, Santiana M, Hsu NY, Du WL, Chen YH, Viktorova EG, Belov G, Brinker A, Storch J, Moore C, Dixon JL, Altan-Bonnet N. Enteroviruses harness the cellular endocytic machinery to remodel the host cell cholesterol landscape for effective viral replication. Cell Host Microbe. 2013 Sep 11;14(3):281-93. doi:10.1016/j.chom.2013.08.002. PubMed PMID: 24034614.
Nchoutmboube JA, Viktorova EG, Scott A, Ford LA, Pei Z, Watkins PA, Ernst R, and Belov GA. Increased long chain acyl-Coa synthetase activity and fatty acid import is linked to membrane synthesis for development of picornavirus replication organelles. PLoS Pathog. 2013; Jun;9(6):e1003401. doi: 10.1371/journal.ppat.1003401. PubMed PMID: 23762027
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Belov GA, Nair V, Hanssen B, Hoyt F, Fischer E and Ehrenfeld E. Complex Dynamic Development of Poliovirus Membranous Replication Complexes. J. Virol. 2012. 86(1):302-12
Nai-Yun H, Ilnytska O, Belov G, Santiana M, Ying-Han C, Kaushik-Basu N, Balla T, Ehrenfeld E, van Kuppeveld F, and Altan-Bonnet N. Viral Reorganization of the Secretory Pathway Generates Distinct Organelles for RNA Replication Cell. 2010;141(5):799-811
Please address all the questions about applying
to the graduate program to George Belov