Role of NS1 and TLR3 in Pathogenesis and Immunity of WNV

Overview

Journal Viruses

Publisher MDPI

Specialty Microbiology

Date 2019 Jul 7

PMID 31277274

Citations 6

Authors

Sameera Patel

Alessandro Sinigaglia

Luisa Barzon

Matteo Fassan

Florian Sparber

Salome LeibundGut-Landmann

Mathias Ackermann

Affiliations

Soon will be listed here.

Abstract

West Nile Virus (WNV) is a mosquito-transmitted flavivirus which causes encephalitis especially in elderly and immunocompromised individuals. Previous studies have suggested the protective role of the Toll-like receptor 3 (TLR3) pathway against WNV entry into the brain, while the WNV non-structural protein 1 (NS1) interferes with the TLR3 signaling pathway, besides being a component of viral genome replication machinery. In this study, we investigated whether immunization with NS1 could protect against WNV neuroinvasion in the context of TLR3 deficiency. We immunized mice with either an intact or deleted TLR3 system (TLR3KO) with WNV envelope glycoprotein (gE) protein, NS1, or a combination of gE and NS1. Immunization with gE or gE/NS1, but not with NS1 alone, induced WNV neutralizing antibodies and protected against WNV brain invasion and inflammation. The presence of intact TLR3 signaling had no apparent effect on WNV brain invasion. However, mock-immunized TLR3KO mice had higher inflammatory cell invasion upon WNV brain infection than NS1-immunized TLR3KO mice and wild type mice. Thus, immunization against NS1 may reduce brain inflammation in a context of TLR3 signaling deficiency.

Citing Articles

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References

Wang T, Anderson J, Magnarelli L, Wong S, Koski R, Fikrig E . Immunization of mice against West Nile virus with recombinant envelope protein. J Immunol. 2001; 167(9):5273-7. DOI: 10.4049/jimmunol.167.9.5273. View

Tesh R, Arroyo J, Travassos da Rosa A, Guzman H, Xiao S, P Monath T . Efficacy of killed virus vaccine, live attenuated chimeric virus vaccine, and passive immunization for prevention of West Nile virus encephalitis in hamster model. Emerg Infect Dis. 2002; 8(12):1392-7. PMC: 2738528. DOI: 10.3201/eid0812.020229. View

Arroyo J, Miller C, Catalan J, Myers G, Ratterree M, Trent D . ChimeriVax-West Nile virus live-attenuated vaccine: preclinical evaluation of safety, immunogenicity, and efficacy. J Virol. 2004; 78(22):12497-507. PMC: 525070. DOI: 10.1128/JVI.78.22.12497-12507.2004. View

Wang T, Town T, Alexopoulou L, Anderson J, Fikrig E, Flavell R . Toll-like receptor 3 mediates West Nile virus entry into the brain causing lethal encephalitis. Nat Med. 2004; 10(12):1366-73. DOI: 10.1038/nm1140. View

Iglesias M, Frenkiel M, Mollier K, Souque P, Despres P, Charneau P . A single immunization with a minute dose of a lentiviral vector-based vaccine is highly effective at eliciting protective humoral immunity against West Nile virus. J Gene Med. 2005; 8(3):265-74. DOI: 10.1002/jgm.837. View

Chung K, Nybakken G, Thompson B, Engle M, Marri A, Fremont D . Antibodies against West Nile Virus nonstructural protein NS1 prevent lethal infection through Fc gamma receptor-dependent and -independent mechanisms. J Virol. 2006; 80(3):1340-51. PMC: 1346945. DOI: 10.1128/JVI.80.3.1340-1351.2006. View

P Monath T, Liu J, Kanesa-Thasan N, Myers G, Nichols R, Deary A . A live, attenuated recombinant West Nile virus vaccine. Proc Natl Acad Sci U S A. 2006; 103(17):6694-9. PMC: 1436023. DOI: 10.1073/pnas.0601932103. View

Kanai R, Kar K, Anthony K, Gould L, Ledizet M, Fikrig E . Crystal structure of west nile virus envelope glycoprotein reveals viral surface epitopes. J Virol. 2006; 80(22):11000-8. PMC: 1642136. DOI: 10.1128/JVI.01735-06. View

Samuel M, Diamond M . Pathogenesis of West Nile Virus infection: a balance between virulence, innate and adaptive immunity, and viral evasion. J Virol. 2006; 80(19):9349-60. PMC: 1617273. DOI: 10.1128/JVI.01122-06. View

10.

Watts D, Tesh R, Siirin M, da Rosa A, Newman P, Clements D . Efficacy and durability of a recombinant subunit West Nile vaccine candidate in protecting hamsters from West Nile encephalitis. Vaccine. 2006; 25(15):2913-8. PMC: 1876746. DOI: 10.1016/j.vaccine.2006.08.008. View

11.

Chung K, Liszewski M, Nybakken G, Davis A, Townsend R, Fremont D . West Nile virus nonstructural protein NS1 inhibits complement activation by binding the regulatory protein factor H. Proc Natl Acad Sci U S A. 2006; 103(50):19111-6. PMC: 1664712. DOI: 10.1073/pnas.0605668103. View

12.

Chu J, Chiang C, Ng M . Immunization of flavivirus West Nile recombinant envelope domain III protein induced specific immune response and protection against West Nile virus infection. J Immunol. 2007; 178(5):2699-705. DOI: 10.4049/jimmunol.178.5.2699. View

13.

McDonald W, Huleatt J, Foellmer H, Hewitt D, Tang J, Desai P . A West Nile virus recombinant protein vaccine that coactivates innate and adaptive immunity. J Infect Dis. 2007; 195(11):1607-17. DOI: 10.1086/517613. View

14.

Kramer L, Styer L, Ebel G . A global perspective on the epidemiology of West Nile virus. Annu Rev Entomol. 2007; 53:61-81. DOI: 10.1146/annurev.ento.53.103106.093258. View

15.

Martina B, Koraka P, van den Doel P, van Amerongen G, Rimmelzwaan G, Osterhaus A . Immunization with West Nile virus envelope domain III protects mice against lethal infection with homologous and heterologous virus. Vaccine. 2007; 26(2):153-7. PMC: 7127062. DOI: 10.1016/j.vaccine.2007.10.055. View

16.

Martin J, Pierson T, Hubka S, Rucker S, Gordon I, Enama M . A West Nile virus DNA vaccine induces neutralizing antibody in healthy adults during a phase 1 clinical trial. J Infect Dis. 2008; 196(12):1732-40. PMC: 2714735. DOI: 10.1086/523650. View

17.

Kong K, Delroux K, Wang X, Qian F, Arjona A, Malawista S . Dysregulation of TLR3 impairs the innate immune response to West Nile virus in the elderly. J Virol. 2008; 82(15):7613-23. PMC: 2493309. DOI: 10.1128/JVI.00618-08. View

18.

Wilson J, de Sessions P, Leon M, Scholle F . West Nile virus nonstructural protein 1 inhibits TLR3 signal transduction. J Virol. 2008; 82(17):8262-71. PMC: 2519649. DOI: 10.1128/JVI.00226-08. View

19.

Daffis S, Samuel M, Suthar M, Gale Jr M, Diamond M . Toll-like receptor 3 has a protective role against West Nile virus infection. J Virol. 2008; 82(21):10349-58. PMC: 2573187. DOI: 10.1128/JVI.00935-08. View

20.

Diamond M, Pierson T, Fremont D . The structural immunology of antibody protection against West Nile virus. Immunol Rev. 2008; 225:212-25. PMC: 2646609. DOI: 10.1111/j.1600-065X.2008.00676.x. View