MRCE Project Abstract

2009

Defining Mechanisms by Which Complement Activation Coordinates a Protective Immune Response against Infection by West Nile Virus

Michael Diamond, MD, PhD

West Nile Virus (WNV) is an emerging mosquito-borne flavivirus that causes fatal outbreaks of encephalitis in Europe, Asia, the Middle East and the United States of America. Using genetically deficient mice we recently demonstrated that a deficiency of the complement components C1q or C4 leads to a disseminated, fatal WNV infection. Based on these observations, we propose to directly determine how activation of the classical and lectin complement pathways inhibits WNV infection. These results may be applicable to other related NIAID Category A and B flavivirus human pathogens.

MRCE Publications

Human monoclonal antibodies against West Nile virus induced by natural infection neutralize at a postattachment step. Vogt MR, Moesker B, Goudsmit J, Jongeneelen M, Austin SK, Oliphant T, Nelson S, Pierson TC, Wilschut J, Throsby M, Diamond MS. J Virol: 2009 Jul;83(13):6494-507.

The immune adaptor molecule SARM modulates TNF-{alpha} production and microglia activation in the brainstem and restricts West Nile virus pathogenesis. Szretter KJ, Samuel MA, Gilfillan S, Fuchs A, Colonna M, Diamond MS. J Virol: 2009 Jul 8.

Virus and host determinants of West Nile virus pathogenesis. Diamond MS. PLoS Pathog: 2009 Jun;5(6):e1000452.

A therapeutic antibody against west nile virus neutralizes infection by blocking fusion within endosomes. Thompson BS, Moesker B, Smit JM, Wilschut J, Diamond MS, Fremont DH. PLoS Pathog: 2009 May;5(5):e1000453.

The host immunologic response to West Nile encephalitis virus. Diamond MS, Mehlhop E, Oliphant T, Samuel MA. Front Biosci: 2009 Jan 1;14:3024-34.

Batf3 deficiency reveals a critical role for CD8alpha+ dendritic cells in cytotoxic T cell immunity. Hildner K, Edelson BT, Purtha WE, Diamond M, Matsushita H, Kohyama M, Calderon B, Schraml BU, Unanue ER, Diamond MS, Schreiber RD, Murphy TL, Murphy KM. Science: 2008 Nov 14;322(5904):1097-100.

Early B-cell activation after West Nile virus infection requires alpha/beta interferon but not antigen receptor signaling. Purtha WE, Chachu KA, Virgin HW 4th, Diamond MS. J Virol: 2008 Nov;82(22):10964-74.

The structural immunology of antibody protection against West Nile virus. Diamond MS, Pierson TC, Fremont DH. Immunol Rev: 2008 Oct;225:212-25.

The structural immunology of antibody protection against West Nile virus. Diamond MS, Pierson TC, Fremont DH. Immunol Rev: 2008 Oct;225(1):212-25.

Tumor necrosis factor alpha protects against lethal West Nile virus infection by promoting trafficking of mononuclear leukocytes into the central nervous system. Shrestha B, Zhang B, Purtha WE, Klein RS, Diamond MS. J Virol: 2008 Sep;82(18):8956-64.

CXCR4 antagonism increases T cell trafficking in the central nervous system and improves survival from West Nile virus encephalitis. McCandless EE, Zhang B, Diamond MS, Klein RS. Proc Natl Acad Sci U S A: 2008 Aug 12;105(32):11270-5.

Interferon regulatory factor (IRF)-7 induces the antiviral interferon (IFN)-{alpha} response and protects against lethal West Nile virus infection. Daffis S, Samuel MA, Suthar MS, Keller BC, Gale M Jr, Diamond MS. J Virol: 2008 Jun 18 [.

Immunological headgear: antiviral immune responses protect against neuroinvasive West Nile virus. Klein RS, Diamond MS. Trends Mol Med: 2008 Jun 6.

Molecular mechanisms of antibody-mediated neutralisation of flavivirus. Pierson TC, Diamond MS. Expert Rev Mol Med: 2008 May 12;10:e12.

The relative contribution of antibody and CD8+ T cells to vaccine immunity against West Nile encephalitis virus. Bimmi Shresthaa, Terry Ngb, Hsien-Jue Chub, Michelle Nolla and Michael S Diamond. Vaccine: 2008 Apr 7;26(16):2020-33.

CXCR3 Mediates Region-Specific Antiviral T Cell Trafficking within the Central Nervous System during West Nile Virus Encephalitis. Zhang B, Chan YK, Lu B, Diamond MS, Klein RS. J Immunol: 2008; 180(4):2641-9.

Binding of a neutralizing antibody to dengue virus alters the arrangement of surface glycoproteins. Lok SM, Kostyuchenko V, Nybakken GE, Holdaway HA, Battisti AJ, Sukupolvi-Petty S, Sedlak D, Fremont DH, Chipman PR, Roehrig JT, Diamond MS, Kuhn RJ, Rossmann MG. Nat Struct Mol Biol: 2008 Mar;15(3):312-7.

Defining the Levels of Secreted Non-Structural Protein NS1 After West Nile Virus Infection in Cell Culture and Mice. Kyung Min Chung and Michael S Diamond. Journal of Medical Virology: 2008;80:547-556.

The molecular basis of antibody protection against West Nile virus. Mehlhop E, Diamond MS. Curr Top Microbiol Immunol: 2008;317:125-53.

Complement protein c1q inhibits antibody-dependent enhancement of flavivirus infection in an IgG subclass-specific manner. Mehlhop E, Ansarah-Sobrinho C, Johnson S, Engle M, Fremont DH, Pierson TC, Diamond MS. Cell Host Microbe: 2007;2(6):417-26.

Secreted NS1 of Dengue Virus Attaches to the Surface of Cells via Interactions with Heparan Sulfate and Chondroitin Sulfate E. Avirutnan P, Zhang L, Punyadee N, Manuyakom A, Puttikhunt C, Kasinrerk W, Malasit P, Atkinson P, Diamond MS. PloS Pathog: 2007;3(11):1798-1812.

Type- and Sub-Complex-Specific Neutralizing Antibodies Against Domain III of Dengue Virus Type-2 Envelope Protein Recognize Adjacent Epitopes. Sukupolvi-Petty S, Austin SK, Purtha WE, Oliphant T, Nybakken GE, Schlesinger JJ, Roehrig JT, Gromowski GD, Barrett AD, Fremont DH, Diamond MS. J Virol: 2007;81(23):12816-12826.

Fas Ligand interactions contribute to CD8+ T cell-mediated control of West Nile virus infection in the central nervous system. Shrestha B, Diamond MS. Journal of Virology: 2007;81(21):11749-11757.

Induction of Epitope-Specific Neutralizing Antibodies against West Nile virus. Oliphant T, Nybakken GE, Austin SK, Xu Q, Bramson J, Loeb M, Throsby M, Fremont DH, Pierson TC, Diamond MS. J Virol: 2007;81(21):11828-11839.

CD40-CD40 Ligand Interactions Promote Trafficking of CD8+ T Cells into the Brain and Protection against West Nile Virus Encephalitis. Sitati E, McCandless EE, Klein RS, Diamond MS. J Virol: 2007;81(18):9801-9811.

Antibody recognition of cell surface-associated NS1 triggers Fc-y receptor mediated phagocytosis and clearance of WNV infected cells. Kyung Min Chung, Bruce S Thompson, Daved H Fremont, and Michael S Diamond. J Virol: 2007;81(17):9551-9555.

Antigen-specific cytotoxic T lymphocytes protect against lethal West Nile virus encephalitis. Purtha WE, Myers N, Mitaksov V, Sitati E, Connolly J, Fremont DH, Hansen TH, Diamond MS. Eur J Immunol : 2007;37:1845-1854.

The molecular basis of antibody-mediated neutralization of West Nile virus. Theodore Oliphant, Michael S Diamond. Expert Opin Biol Ther: 2007;7(6):885-892.

Defining limits of humanized neutralizing monoclonal antibody treatment for West Nile virus neurological infection in a hamster model. Morrey JD, Siddharthan V, Olsen AL, Wang H, Julaner JG, Hall JO, Li H, Nordstrom JL, Koenig S, Johnson S, Diamond MS. Antimicrob Agents Chemother: 2007;51(7):2396-2402.

West Nile virus nonstructural protein NS1 inhibits complement activation by binding the regulatory protein factor H. Chung KM, Liszewski MK, Nybakken G, Davis AE, Townsend RR, Fremont DH, Atkinson JP, Diamond MS. Proc Natl Acad Sci U S A: 2006;103(50):19111-19116.

CD4+ T Cell Responses are Required for Clearance for West Nile Virus from the Central Nervous System. Sitati EM, Diamond MS. J Virol: 2006;80(24):12060-12069.

Pathogenesis of West Nile Virus Infection: a Balance between Virulence, Innate and Adaptive Immunity, and Viral Evasion. Samuel MA, Diamond MS. J Virol: 2006;80(19):9349-9360 Review.

Crystal structure of the West Nile virus envelope glycoprotein. Nybakken GE, Nelson CA, Chen BR, Diamond MS, Fremont DH. J Virol: 2006;80(23):11467-11474.

Antibody recognition and neutralization determinants on domains I and II of West Nile Virus envelope protein. Oliphant T, Nybakken GE, Engle M, Xu Q, Nelson CA, Sukupolvi-Petty S, Marri A, Lachmi BE, Olshevsky U, Fremont DH, Pierson TC, Diamond MS. J Virol: 2006;80(24):12149-12159.

Protective immune responses against West Nile Virus are primed by distinct complement activation pathways. Mehlhop E, Diamond MS. J Exp Med: 2006;203(5):1371-1381.

Antibodies against West Nile Virus nonstructural protein NS1 prevent lethal infection through Fc gamma receptor-dependent and -independent mechanisms. Chung KM, Nybakken GE, Thompson BS, Engle MJ, Marri A, Fremont DH, Diamond MS. J Virol: 2006;80(3):1340-1351.

Structure, expression and intracellular localization of the SARS-CoV accessory proteins 7a and 7b. Pekosz A, Schaecher SR, Diamond MS, Fremont DH, Sims AC, Baric RS. Adv Exp Med Biol: 2006;581:115-120.

Structural basis of West Nile Virus neutralization by a therapeutic antibody. Nybakken GE, Oliphant T, Johnson S, Burke S, Diamond MS, Fremont DH. Nature: 2005;437:764-769.

Complement activation is required for induction of a protective antibody response against West Nile virus infection. Mehlhop E, Whitby K, Oliphant T, Marri A, Engle M, Diamond MS . J Virol: 2005;79(12):7466-7477.

Development of a humanized monoclonal antibody with therapeutic potential against West Nile virus. Oliphant T, Engle M, Nybakken GE, Doane C, Johnson S, Huang L, Gorlatov S, Mehlhop E, Marri A, Chung KM, Ebel GD, Kramer LD, Fremont DH, Diamond MS. Nat Med: 2005;11(5):522-530.

Role of CD8+ T cells in control of West Nile virus infection. Shrestha B, Diamond MS. J Virol: 2004;78(15):8312-8321.

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