Modulation of the Host Immune Response by Respiratory Syncytial Virus Proteins

Overview

Journal J Microbiol

Specialty Microbiology

Date 2017 Mar 1

PMID 28243940

Citations 19

Authors

Megan E Schmidt

Steven M Varga

Affiliations

Soon will be listed here.

Abstract

Respiratory syncytial virus (RSV) causes severe respiratory disease in both the very young and the elderly. Nearly all individuals become infected in early childhood, and reinfections with the virus are common throughout life. Despite its clinical impact, there remains no licensed RSV vaccine. RSV infection in the respiratory tract induces an inflammatory response by the host to facilitate efficient clearance of the virus. However, the host immune response also contributes to the respiratory disease observed following an RSV infection. RSV has evolved several mechanisms to evade the host immune response and promote virus replication through interactions between RSV proteins and immune components. In contrast, some RSV proteins also play critical roles in activating, rather than suppressing, host immunity. In this review, we discuss the interactions between individual RSV proteins and host factors that modulate the immune response and the implications of these interactions for the course of an RSV infection.

Citing Articles

Intranasal Vaccination with a Respiratory-Syncytial-Virus-Based Virus-like Particle Displaying the G Protein Conserved Region Induces Severe Weight Loss and Pathology upon Challenge with Wildtype Respiratory Syncytial Virus.

Terhuja M, Siddappa M, Lamichhane P, Meshram C, Snider T, Ritchey J Viruses. 2024; 16(6).

PMID: 38932136 PMC: 11209524. DOI: 10.3390/v16060843.

Immune Response to Respiratory Viral Infections.

Gambadauro A, Galletta F, Li Pomi A, Manti S, Piedimonte G Int J Mol Sci. 2024; 25(11).

PMID: 38892370 PMC: 11172738. DOI: 10.3390/ijms25116178.

Repurposing Axl Kinase Inhibitors for the Treatment of Respiratory Syncytial Virus Infection.

Zhang D, Zhao Y, You X, He S, Li E Antimicrob Agents Chemother. 2023; 67(3):e0148722.

PMID: 36853000 PMC: 10019287. DOI: 10.1128/aac.01487-22.

Viral Genetic Determinants of Prolonged Respiratory Syncytial Virus Infection Among Infants in a Healthy Term Birth Cohort.

Lawless D, McKennan C, Das S, Junier T, Xu Z, Anderson L J Infect Dis. 2022; 227(10):1194-1202.

PMID: 36375000 PMC: 10175068. DOI: 10.1093/infdis/jiac442.

Enhancing Anti-G Antibody Induction by a Live Single-Cycle Prefusion F-Expressing RSV Vaccine Improves In Vitro and In Vivo Efficacy.

Lamichhane P, Terhuja M, Snider T, Oomens A Viruses. 2022; 14(11).

PMID: 36366572 PMC: 9697216. DOI: 10.3390/v14112474.

References

Swedan S, Musiyenko A, Barik S . Respiratory syncytial virus nonstructural proteins decrease levels of multiple members of the cellular interferon pathways. J Virol. 2009; 83(19):9682-93. PMC: 2748017. DOI: 10.1128/JVI.00715-09. View

Tripp R, Moore D, Jones L, Sullender W, Winter J, Anderson L . Respiratory syncytial virus G and/or SH protein alters Th1 cytokines, natural killer cells, and neutrophils responding to pulmonary infection in BALB/c mice. J Virol. 1999; 73(9):7099-107. PMC: 104227. DOI: 10.1128/JVI.73.9.7099-7107.1999. View

Gan S, Tan E, Lin X, Yu D, Wang J, Tan G . The small hydrophobic protein of the human respiratory syncytial virus forms pentameric ion channels. J Biol Chem. 2012; 287(29):24671-89. PMC: 3397895. DOI: 10.1074/jbc.M111.332791. View

Graham B, Bunton L, Wright P, Karzon D . Role of T lymphocyte subsets in the pathogenesis of primary infection and rechallenge with respiratory syncytial virus in mice. J Clin Invest. 1991; 88(3):1026-33. PMC: 295511. DOI: 10.1172/JCI115362. View

Haynes L, Jones L, Barskey A, Anderson L, Tripp R . Enhanced disease and pulmonary eosinophilia associated with formalin-inactivated respiratory syncytial virus vaccination are linked to G glycoprotein CX3C-CX3CR1 interaction and expression of substance P. J Virol. 2003; 77(18):9831-44. PMC: 224581. DOI: 10.1128/jvi.77.18.9831-9844.2003. View

Puthothu B, Forster J, Heinzmann A, Krueger M . TLR-4 and CD14 polymorphisms in respiratory syncytial virus associated disease. Dis Markers. 2007; 22(5-6):303-8. PMC: 3851085. DOI: 10.1155/2006/865890. View

Spann K, Tran K, Chi B, Rabin R, Collins P . Suppression of the induction of alpha, beta, and lambda interferons by the NS1 and NS2 proteins of human respiratory syncytial virus in human epithelial cells and macrophages [corrected]. J Virol. 2004; 78(8):4363-9. PMC: 374276. DOI: 10.1128/jvi.78.8.4363-4369.2004. View

Hall C, Long C, Schnabel K . Respiratory syncytial virus infections in previously healthy working adults. Clin Infect Dis. 2001; 33(6):792-6. DOI: 10.1086/322657. View

Fujisawa T, Chang M, Velichko S, Thai P, Hung L, Huang F . NF-κB mediates IL-1β- and IL-17A-induced MUC5B expression in airway epithelial cells. Am J Respir Cell Mol Biol. 2010; 45(2):246-52. PMC: 3175554. DOI: 10.1165/rcmb.2009-0313OC. View

10.

Narasaraju T, Yang E, Perumal Samy R, Ng H, Poh W, Liew A . Excessive neutrophils and neutrophil extracellular traps contribute to acute lung injury of influenza pneumonitis. Am J Pathol. 2011; 179(1):199-210. PMC: 3123873. DOI: 10.1016/j.ajpath.2011.03.013. View

11.

Polack F, Irusta P, Hoffman S, Schiatti M, Melendi G, Delgado M . The cysteine-rich region of respiratory syncytial virus attachment protein inhibits innate immunity elicited by the virus and endotoxin. Proc Natl Acad Sci U S A. 2005; 102(25):8996-9001. PMC: 1157014. DOI: 10.1073/pnas.0409478102. View

12.

Mitra R, Baviskar P, Duncan-Decocq R, Patel D, Oomens A . The human respiratory syncytial virus matrix protein is required for maturation of viral filaments. J Virol. 2012; 86(8):4432-43. PMC: 3318654. DOI: 10.1128/JVI.06744-11. View

13.

Cespedes P, Bueno S, Ramirez B, Gomez R, Riquelme S, Palavecino C . Surface expression of the hRSV nucleoprotein impairs immunological synapse formation with T cells. Proc Natl Acad Sci U S A. 2014; 111(31):E3214-23. PMC: 4128097. DOI: 10.1073/pnas.1400760111. View

14.

Munir S, Le Nouen C, Luongo C, Buchholz U, Collins P, Bukreyev A . Nonstructural proteins 1 and 2 of respiratory syncytial virus suppress maturation of human dendritic cells. J Virol. 2008; 82(17):8780-96. PMC: 2519638. DOI: 10.1128/JVI.00630-08. View

15.

Saitoh T, Komano J, Saitoh Y, Misawa T, Takahama M, Kozaki T . Neutrophil extracellular traps mediate a host defense response to human immunodeficiency virus-1. Cell Host Microbe. 2012; 12(1):109-16. DOI: 10.1016/j.chom.2012.05.015. View

16.

Roberts S, Lichtenstein D, Ball L, Wertz G . The membrane-associated and secreted forms of the respiratory syncytial virus attachment glycoprotein G are synthesized from alternative initiation codons. J Virol. 1994; 68(7):4538-46. PMC: 236380. DOI: 10.1128/JVI.68.7.4538-4546.1994. View

17.

Suhara W, Yoneyama M, Kitabayashi I, Fujita T . Direct involvement of CREB-binding protein/p300 in sequence-specific DNA binding of virus-activated interferon regulatory factor-3 holocomplex. J Biol Chem. 2002; 277(25):22304-13. DOI: 10.1074/jbc.M200192200. View

18.

Jansen A, Sanders E, Hoes A, van Loon A, Hak E . Influenza- and respiratory syncytial virus-associated mortality and hospitalisations. Eur Respir J. 2007; 30(6):1158-66. DOI: 10.1183/09031936.00034407. View

19.

Lo M, Brazas R, Holtzman M . Respiratory syncytial virus nonstructural proteins NS1 and NS2 mediate inhibition of Stat2 expression and alpha/beta interferon responsiveness. J Virol. 2005; 79(14):9315-9. PMC: 1168759. DOI: 10.1128/JVI.79.14.9315-9319.2005. View

20.

Whelan J, Tran K, van Rossum D, Teng M . Identification of Respiratory Syncytial Virus Nonstructural Protein 2 Residues Essential for Exploitation of the Host Ubiquitin System and Inhibition of Innate Immune Responses. J Virol. 2016; 90(14):6453-6463. PMC: 4936147. DOI: 10.1128/JVI.00423-16. View