Viruses and Metabolism: The Effects of Viral Infections and Viral Insulins on Host Metabolism

Overview

Journal Annu Rev Virol

Publisher Annual Reviews

Specialty Microbiology

Date 2021 Sep 29

PMID 34586876

Citations 43

Authors

Khyati Girdhar

Amaya Powis

Amol Raisingani

Martina Chrudinova

Ruixu Huang

Tu Tran

Kaan Sevgi

Yusuf Dogus Dogru

Emrah Altindis

Affiliations

Soon will be listed here.

Abstract

Over the past decades, there have been tremendous efforts to understand the cross-talk between viruses and host metabolism. Several studies have elucidated the mechanisms through which viral infections manipulate metabolic pathways including glucose, fatty acid, protein, and nucleotide metabolism. These pathways are evolutionarily conserved across the tree of life and extremely important for the host's nutrient utilization and energy production. In this review, we focus on host glucose, glutamine, and fatty acid metabolism and highlight the pathways manipulated by the different classes of viruses to increase their replication. We also explore a new system of viral hormones in which viruses mimic host hormones to manipulate the host endocrine system. We discuss viral insulin/IGF-1-like peptides and their potential effects on host metabolism. Together, these pathogenesis mechanisms targeting cellular signaling pathways create a multidimensional network of interactions between host and viral proteins. Defining and better understanding these mechanisms will help us to develop new therapeutic tools to prevent and treat viral infections.

Citing Articles

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References

Ahlers L, Bastos R, Hiroyasu A, Goodman A . Invertebrate Iridescent Virus 6, a DNA Virus, Stimulates a Mammalian Innate Immune Response through RIG-I-Like Receptors. PLoS One. 2016; 11(11):e0166088. PMC: 5100955. DOI: 10.1371/journal.pone.0166088. View

Hou W, Cruz-Cosme R, Armstrong N, Obwolo L, Wen F, Hu W . Molecular cloning and characterization of the genes encoding the proteins of Zika virus. Gene. 2017; 628:117-128. PMC: 5729740. DOI: 10.1016/j.gene.2017.07.049. View

Navale A, Paranjape A . Glucose transporters: physiological and pathological roles. Biophys Rev. 2017; 8(1):5-9. PMC: 5425736. DOI: 10.1007/s12551-015-0186-2. View

Passalacqua K, Lu J, Goodfellow I, Kolawole A, Arche J, Maddox R . Glycolysis Is an Intrinsic Factor for Optimal Replication of a Norovirus. mBio. 2019; 10(2). PMC: 6414699. DOI: 10.1128/mBio.02175-18. View

Yu Y, Maguire T, Alwine J . Human cytomegalovirus infection induces adipocyte-like lipogenesis through activation of sterol regulatory element binding protein 1. J Virol. 2012; 86(6):2942-9. PMC: 3302344. DOI: 10.1128/JVI.06467-11. View

Jassey A, Liu C, Changou C, Richardson C, Hsu H, Lin L . Hepatitis C Virus Non-Structural Protein 5A (NS5A) Disrupts Mitochondrial Dynamics and Induces Mitophagy. Cells. 2019; 8(4). PMC: 6523690. DOI: 10.3390/cells8040290. View

Fernie A, Carrari F, Sweetlove L . Respiratory metabolism: glycolysis, the TCA cycle and mitochondrial electron transport. Curr Opin Plant Biol. 2004; 7(3):254-61. DOI: 10.1016/j.pbi.2004.03.007. View

Lopez-Bueno A, Mavian C, Labella A, Castro D, Borrego J, Alcami A . Concurrence of Iridovirus, Polyomavirus, and a Unique Member of a New Group of Fish Papillomaviruses in Lymphocystis Disease-Affected Gilthead Sea Bream. J Virol. 2016; 90(19):8768-79. PMC: 5021401. DOI: 10.1128/JVI.01369-16. View

Sackton T, Clark N . Convergent evolution in the genomics era: new insights and directions. Philos Trans R Soc Lond B Biol Sci. 2019; 374(1777):20190102. PMC: 6560275. DOI: 10.1098/rstb.2019.0102. View

10.

Shafee T, Lay F, Phan T, Anderson M, Hulett M . Convergent evolution of defensin sequence, structure and function. Cell Mol Life Sci. 2016; 74(4):663-682. PMC: 11107677. DOI: 10.1007/s00018-016-2344-5. View

11.

Minot S, Bryson A, Chehoud C, Wu G, Lewis J, Bushman F . Rapid evolution of the human gut virome. Proc Natl Acad Sci U S A. 2013; 110(30):12450-5. PMC: 3725073. DOI: 10.1073/pnas.1300833110. View

12.

Sanchez E, Carroll P, Thalhofer A, Lagunoff M . Latent KSHV Infected Endothelial Cells Are Glutamine Addicted and Require Glutaminolysis for Survival. PLoS Pathog. 2015; 11(7):e1005052. PMC: 4510438. DOI: 10.1371/journal.ppat.1005052. View

13.

Ajaz S, McPhail M, Singh K, Mujib S, Trovato F, Napoli S . Mitochondrial metabolic manipulation by SARS-CoV-2 in peripheral blood mononuclear cells of patients with COVID-19. Am J Physiol Cell Physiol. 2020; 320(1):C57-C65. PMC: 7816428. DOI: 10.1152/ajpcell.00426.2020. View

14.

Gendrault J, Steffan A, Bingen A, KIRN A . Penetration and uncoating of frog virus 3 (FV3) in cultured rat Kupffer cells. Virology. 1981; 112(2):375-84. DOI: 10.1016/0042-6822(81)90284-1. View

15.

Zwerschke W, Mazurek S, Massimi P, Banks L, Eigenbrodt E, Jansen-Durr P . Modulation of type M2 pyruvate kinase activity by the human papillomavirus type 16 E7 oncoprotein. Proc Natl Acad Sci U S A. 1999; 96(4):1291-6. PMC: 15456. DOI: 10.1073/pnas.96.4.1291. View

16.

Spencer C, Schafer X, Moorman N, Munger J . Human cytomegalovirus induces the activity and expression of acetyl-coenzyme A carboxylase, a fatty acid biosynthetic enzyme whose inhibition attenuates viral replication. J Virol. 2011; 85(12):5814-24. PMC: 3126312. DOI: 10.1128/JVI.02630-10. View

17.

Zhang M, Liu J, Li M, Zhang S, Lu Y, Liang Y . Insulin-like growth factor 1/insulin-like growth factor 1 receptor signaling protects against cell apoptosis through the PI3K/AKT pathway in glioblastoma cells. Exp Ther Med. 2018; 16(2):1477-1482. PMC: 6090237. DOI: 10.3892/etm.2018.6336. View

18.

Hung Y, Teragawa C, Kosaisawe N, Gillies T, Pargett M, Minguet M . Akt regulation of glycolysis mediates bioenergetic stability in epithelial cells. Elife. 2017; 6. PMC: 5730373. DOI: 10.7554/eLife.27293. View

19.

Kapadia S, Chisari F . Hepatitis C virus RNA replication is regulated by host geranylgeranylation and fatty acids. Proc Natl Acad Sci U S A. 2005; 102(7):2561-6. PMC: 549027. DOI: 10.1073/pnas.0409834102. View

20.

Alcami A, Smith G . A soluble receptor for interleukin-1 beta encoded by vaccinia virus: a novel mechanism of virus modulation of the host response to infection. Cell. 1992; 71(1):153-67. DOI: 10.1016/0092-8674(92)90274-g. View