Immune Netw.  2013 Oct;13(5):163-167. 10.4110/in.2013.13.5.163.

Respiratory Syncytial Virus (RSV) Modulation at the Virus-Host Interface Affects Immune Outcome and Disease Pathogenesis

Affiliations
  • 1Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens GA 30602, USA. ratripp@uga.edu

Abstract

The dynamics of the virus-host interface in the response to respiratory virus infection is not well-understood; however, it is at this juncture that host immunity to infection evolves. Respiratory viruses have been shown to modulate the host response to gain a replication advantage through a variety of mechanisms. Viruses are parasites and must co-opt host genes for replication, and must interface with host cellular machinery to achieve an optimal balance between viral and cellular gene expression. Host cells have numerous strategies to resist infection, replication and virus spread, and only recently are we beginning to understand the network and pathways affected. The following is a short review article covering some of the studies associated with the Tripp laboratory that have addressed how respiratory syncytial virus (RSV) operates at the virus-host interface to affects immune outcome and disease pathogenesis.

Keyword

RSV; Virus-host interface; Disease intervention

MeSH Terms

Gene Expression
Imidazoles
Nitro Compounds
Parasites
Respiratory Syncytial Viruses*
Viruses
Imidazoles
Nitro Compounds

Reference

1. Cate TR. Impact of influenza and other community-acquired viruses. Semin Respir Infect. 1998; 13:17–23.
2. Greenberg SB. Rhinovirus and coronavirus infections. Semin Respir Crit Care Med. 2007; 28:182–192.
Article
3. Heikkinen T. Role of viruses in the pathogenesis of acute otitis media. Pediatr Infect Dis J. 2000; 19:S17–S22.
Article
4. Mahony JB, Petrich A, Smieja M. Molecular diagnosis of respiratory virus infections. Crit Rev Clin Lab Sci. 2011; 48:217–249.
Article
5. See H, Wark P. Innate immune response to viral infection of the lungs. Paediatr Respir Rev. 2008; 9:243–250.
Article
6. Bartlett JA, Fischer AJ, McCray PB Jr. Innate immune functions of the airway epithelium. Contrib Microbiol. 2008; 15:147–163.
Article
7. Oshansky CM, Zhang W, Moore E, Tripp RA. The host response and molecular pathogenesis associated with respiratory syncytial virus infection. Future Microbiol. 2009; 4:279–297.
Article
8. Schwarze J, Mackenzie KJ. Novel insights into immune and inflammatory responses to respiratory viruses. Thorax. 2013; 68:108–110.
Article
9. Sajjan US. Susceptibility to viral infections in chronic obstructive pulmonary disease: role of epithelial cells. Curr Opin Pulm Med. 2013; 19:125–132.
Article
10. Averett DR, Fletcher SP, Li W, Webber SE, Appleman JR. The pharmacology of endosomal TLR agonists in viral disease. Biochem Soc Trans. 2007; 35:1468–1472.
Article
11. Sandor F, Buc M. Toll-like receptors. II. Distribution and pathways involved in TLR signalling. Folia Biol (Praha). 2005; 51:188–197.
12. Kurt-Jones EA, Popova L, Kwinn L, Haynes LM, Jones LP, Tripp RA, Walsh EE, Freeman MW, Golenbock DT, Anderson LJ, Finberg RW. Pattern recognition receptors TLR4 and CD14 mediate response to respiratory syncytial virus. Nat Immunol. 2000; 1:398–401.
Article
13. Haynes LM, Moore DD, Kurt-Jones EA, Finberg RW, Anderson LJ, Tripp RA. Involvement of toll-like receptor 4 in innate immunity to respiratory syncytial virus. J Virol. 2001; 75:10730–10737.
Article
14. Awomoyi AA, Rallabhandi P, Pollin TI, Lorenz E, Sztein MB, Boukhvalova MS, Hemming VG, Blanco JC, Vogel SN. Association of TLR4 polymorphisms with symptomatic respiratory syncytial virus infection in high-risk infants and young children. J Immunol. 2007; 179:3171–3177.
Article
15. Goodbourn S, Randall RE. The regulation of type I interferon production by paramyxoviruses. J Interferon Cytokine Res. 2009; 29:539–547.
Article
16. Le Goffic R, Pothlichet J, Vitour D, Fujita T, Meurs E, Chignard M, Si-Tahar M. Cutting Edge: Influenza A virus activates TLR3-dependent inflammatory and RIG-I-dependent antiviral responses in human lung epithelial cells. J Immunol. 2007; 178:3368–3372.
Article
17. Dempoya J, Matsumiya T, Imaizumi T, Hayakari R, Xing F, Yoshida H, Okumura K, Satoh K. Double-stranded RNA induces biphasic STAT1 phosphorylation by both type I interferon (IFN)-dependent and type I IFN-independent pathways. J Virol. 2012; 86:12760–12769.
Article
18. O'Neill LA, Bowie AG. The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling. Nat Rev Immunol. 2007; 7:353–364.
19. Oshansky CM, Krunkosky TM, Barber J, Jones LP, Tripp RA. Respiratory syncytial virus proteins modulate suppressors of cytokine signaling 1 and 3 and the type I interferon response to infection by a toll-like receptor pathway. Viral Immunol. 2009; 22:147–161.
Article
20. Moore EC, Barber J, Tripp RA. Respiratory syncytial virus (RSV) attachment and nonstructural proteins modify the type I interferon response associated with suppressor of cytokine signaling (SOCS) proteins and IFN-stimulated gene-15 (ISG15). Virol J. 2008; 5:116.
Article
21. Tripp RA, Oshansky C, Alvarez R. Cytokines and respiratory syncytial virus infection. Proc Am Thorac Soc. 2005; 2:147–149.
Article
22. Lopusna K, Rezuchova I, Betakova T, Skovranova L, Tomaskova J, Lukacikova L, Kabat P. Interferons lambda, new cytokines with antiviral activity. Acta Virol. 2013; 57:171–179.
Article
23. Kotenko SV. IFN-lambdas. Curr Opin Immunol. 2011; 23:583–590.
24. Hauser MJ, Dlugolenski D, Culhane MR, Wentworth DE, Tompkins SM, Tripp RA. Antiviral responses by Swine primary bronchoepithelial cells are limited compared to human bronchoepithelial cells following influenza virus infection. PLoS One. 2013; 8:e70251.
Article
25. Teng MN. The non-structural proteins of RSV: targeting interferon antagonists for vaccine development. Infect Disord Drug Targets. 2012; 12:129–137.
Article
26. Thornburg NJ, Hayward SL, Crowe JE Jr. Respiratory syncytial virus regulates human microRNAs by using mechanisms involving beta interferon and NF-kappaB. MBio. 2012; 3:e00220–e00212.
27. Munir S, Le Nouen C, Luongo C, Buchholz UJ, Collins PL, Bukreyev A. Nonstructural proteins 1 and 2 of respiratory syncytial virus suppress maturation of human dendritic cells. J Virol. 2008; 82:8780–8796.
Article
28. Tripp RA, Jones L, Anderson LJ. Respiratory syncytial virus G and/or SH glycoproteins modify CC and CXC chemokine mRNA expression in the BALB/c mouse. J Virol. 2000; 74:6227–6229.
Article
29. Tripp RA, Moore D, Anderson LJ. TH(1)- and TH(2)-TYPE cytokine expression by activated t lymphocytes from the lung and spleen during the inflammatory response to respiratory syncytial virus. Cytokine. 2000; 12:801–807.
30. Tripp RA, Moore D, Jones L, Sullender W, Winter J, Anderson LJ. 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; 73:7099–7107.
Article
31. Harcourt J, Alvarez R, Jones LP, Henderson C, Anderson LJ, Tripp RA. Respiratory syncytial virus G protein and G protein CX3C motif adversely affect CX3CR1+ T cell responses. J Immunol. 2006; 176:1600–1608.
Article
32. Tripp RA, Anderson LJ. Cytotoxic T-lymphocyte precursor frequencies in BALB/c mice after acute respiratory syncytial virus (RSV) infection or immunization with a formalin-inactivated RSV vaccine. J Virol. 1998; 72:8971–8975.
Article
33. Bakre A, Mitchell P, Coleman JK, Jones LP, Saavedra G, Teng M, Tompkins SM, Tripp RA. Respiratory syncytial virus modifies microRNAs regulating host genes that affect virus replication. J Gen Virol. 2012; 93:2346–2356.
Article
34. Tripp RA, Jones LP, Haynes LM, Zheng H, Murphy PM, Anderson LJ. CX3C chemokine mimicry by respiratory syncytial virus G glycoprotein. Nat Immunol. 2001; 2:732–738.
Article
35. Haynes LM, Jones LP, Barskey A, Anderson LJ, Tripp RA. 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; 77:9831–9844.
Article
36. Tripp RA, Dakhama A, Jones LP, Barskey A, Gelfand EW, Anderson LJ. The G glycoprotein of respiratory syncytial virus depresses respiratory rates through the CX3C motif and substance P. J Virol. 2003; 77:6580–6584.
Article
37. Li XQ, Fu ZF, Alvarez R, Henderson C, Tripp RA. Respiratory syncytial virus (RSV) infects neuronal cells and processes that innervate the lung by a process involving RSV G protein. J Virol. 2006; 80:537–540.
Article
38. Zhang W, Choi Y, Haynes LM, Harcourt JL, Anderson LJ, Jones LP, Tripp RA. Vaccination to induce antibodies blocking the CX3C-CX3CR1 interaction of respiratory syncytial virus G protein reduces pulmonary inflammation and virus replication in mice. J Virol. 2010; 84:1148–1157.
Article
39. Kauvar LM, Harcourt JL, Haynes LM, Tripp RA. Therapeutic targeting of respiratory syncytial virus G-protein. Immunotherapy. 2010; 2:655–661.
Article
40. Miao C, Radu GU, Caidi H, Tripp RA, Anderson LJ, Haynes LM. Treatment with respiratory syncytial virus G glycoprotein monoclonal antibody or F(ab')2 components mediates reduced pulmonary inflammation in mice. J Gen Virol. 2009; 90:1119–1123.
Article
41. Haynes LM, Caidi H, Radu GU, Miao C, Harcourt JL, Tripp RA, Anderson LJ. Therapeutic monoclonal antibody treatment targeting respiratory syncytial virus (RSV) G protein mediates viral clearance and reduces the pathogenesis of RSV infection in BALB/c mice. J Infect Dis. 2009; 200:439–447.
Article
42. Collarini EJ, Lee FE, Foord O, Park M, Sperinde G, Wu H, Harriman WD, Carroll SF, Ellsworth SL, Anderson LJ, Tripp RA, Walsh EE, Keyt BA, Kauvar LM. Potent high-affinity antibodies for treatment and prophylaxis of respiratory syncytial virus derived from B cells of infected patients. J Immunol. 2009; 183:6338–6345.
Article
43. Harcourt JL, Karron RA, Tripp RA. Anti-G protein antibody responses to respiratory syncytial virus infection or vaccination are associated with inhibition of G protein CX3C-CX3CR1 binding and leukocyte chemotaxis. J Infect Dis. 2004; 190:1936–1940.
Article
44. Choi Y, Mason CS, Jones LP, Crabtree J, Jorquera PA, Tripp RA. Antibodies to the central conserved region of respiratory syncytial virus (RSV) G protein block RSV G protein CX3C-CX3CR1 binding and cross-neutralize RSV A and B strains. Viral Immunol. 2012; 25:193–203.
Article
45. Beeler JA, Eichelberger MC. Influenza and respiratory syncytial virus (RSV) vaccines for infants: safety, immunogenicity, and efficacy. Microb Pathog. 2013; 55:9–15.
Article
46. Schmidt AC. Progress in respiratory virus vaccine development. Semin Respir Crit Care Med. 2011; 32:527–540.
Article
47. DeVincenzo JP. The promise, pitfalls and progress of RNA-interference-based antiviral therapy for respiratory viruses. Antivir Ther. 2012; 17:213–225.
Article
48. Alvarez R, Elbashir S, Borland T, Toudjarska I, Hadwiger P, John M, Roehl I, Morskaya SS, Martinello R, Kahn J, Van Ranst M, Tripp RA, DeVincenzo JP, Pandey R, Maier M, Nechev L, Manoharan M, Kotelianski V, Meyers R. RNA interference-mediated silencing of the respiratory syncytial virus nucleocapsid defines a potent antiviral strategy. Antimicrob Agents Chemother. 2009; 53:3952–3962.
Article
49. Zhang W, Tripp RA. RNA interference inhibits respiratory syncytial virus replication and disease pathogenesis without inhibiting priming of the memory immune response. J Virol. 2008; 82:12221–12231.
Article
50. Bakre A, Andersen LE, Meliopoulos V, Coleman K, Yan X, Brooks P, Crabtree J, Tompkins SM, Tripp RA. Identification of host kinase genes required for influenza virus replication and the regulatory role of MicroRNAs. PLoS One. 2013; 8:e66796.
Article
51. Perwitasari O, Yan X, Johnson S, White C, Brooks P, Tompkins SM, Tripp RA. Targeting organic anion transporter 3 with probenecid as a novel anti-influenza a virus strategy. Antimicrob Agents Chemother. 2013; 57:475–483.
Article
52. Meliopoulos VA, Andersen LE, Brooks P, Yan X, Bakre A, Coleman JK, Tompkins SM, Tripp RA. MicroRNA regulation of human protease genes essential for influenza virus replication. PLoS One. 2012; 7:e37169.
Article
53. Meliopoulos VA, Andersen LE, Birrer KF, Simpson KJ, Lowenthal JW, Bean AG, Stambas J, Stewart CR, Tompkins SM, van Beusechem VW, Fraser I, Mhlanga M, Barichievy S, Smith Q, Leake D, Karpilow J, Buck A, Jona G, Tripp RA. Host gene targets for novel influenza therapies elucidated by high-throughput RNA interference screens. FASEB J. 2012; 26:1372–1386.
Article
54. Tran AT, Rahim MN, Ranadheera C, Kroeker A, Cortens JP, Opanubi KJ, Wilkins JA, Coombs KM. Knockdown of specific host factors protects against influenza virus-induced cell death. Cell Death Dis. 2013; 4:e769.
Article
55. Prusty BK, Karlas A, Meyer TF, Rudel T. Genome-wide RNAi screen for viral replication in mammalian cell culture. Methods Mol Biol. 2011; 721:383–395.
Article
56. Panda D, Cherry S. Cell-based genomic screening: elucidating virus-host interactions. Curr Opin Virol. 2012; 2:784–792.
Article
57. Kassner PD. Discovery of novel targets with high throughput RNA interference screening. Comb Chem High Throughput Screen. 2008; 11:175–184.
Article
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