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virology, microbial pathogenesis, immunology

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7264 McDonnell Pediatric Research Building



Research Abstract

The research in the Diamond laboratory focuses on the interface between viral pathogenesis and the host immune response. For several years, we have been primarily focused on two globally important mosquito-borne human pathogens West Nile virus and Dengue virus. Both are single-stranded positive-sense RNA viruses of the same genus (Flavivirus) that cause severe encephalitis and hemorrhagic fever, respectively, in humans and related to a group of viruses that cause human disease worldwide. Recently, we have begun to study another member of the same virus family, hepatitis C, which causes chronic hepatitis, cirrhosis, and hepatocellular carcinoma as well as an emerging alphavirus, Chikungunya virus. Investigations with hepatitis C and Chikungunya viruses are aimed at understanding the epitope specificity of protective neutralizing antibodies against these viruses. To date, studies with West Nile and Dengue viruses have focused on investigating their pathogenesis and the immune system response that control infection. Using in vitro models of infection in primary neurons, macrophages, and dendtitic cells, we are also studying the mechanisms by which West Nile virus causes direct injury to specific cell types, and how the host responds to limit viral replication. Using a mouse model we have defined critical roles for interferon, interferon-stimulated genes, antibody, complement, CD4+, and CD8+ T cells in the control and eradication of West Nile virus infection. Other directions in the Diamond laboratory include understanding how novel innate immune response effector molecules restrict infection of flaviviruses and alphaviruses, systems biology approaches to dissecting innate immunity in the brain, how the innate immune system contributes to the establishment and maintenance of memory B and T cell responses, and how these processes are affected by aging.

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Michael S. Diamond

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Pathogenesis of West Nile encephalitis and Dengue hemorrhagic fever viruses

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Date Last Updated

11/10/2011 10:51 AM


Daffis S, Szretter K, Schriewer J, Li J, Yoon S, Erret J, Lin TY, Schneller S, Zust R, Dong H, Thiel V, Pierson TC, Buller RM, Gale Jr M, Shi PY, and Diamond MS.  2’O methylation of the viral mRNA cap evades host restriction by IFIT family memners. Nature 2010 18:452-456. PMCID: PMC3058805.
Daffis S, Lazear HM, Liu WJ, Audsley M, Engle M, Khromykh AA, Diamond MS. The naturally attenuated Kunjin strain of West Nile virus shows enhanced sensitivity to the host type I interferon response. J Virol. 2011 Mar 16; 85(11):5664-8. PMCID: PMC3094947.
Lazear HM, Pinto AK, Vogt MR, Gale M, and Diamond MS. Interferon-β controls West Nile virus infection and pathogenesis in mice. J Virol. 2011 May 4; 85(14):7186-94. PMCID: PMC3126609
Vogt MR, Dowd KA, Engle M, Tesh RB, Johnson S, Pierson TC, Diamond MS. Poorly neutralizing cross-reactive antibodies against the fusion loop of West Nile virus envelope protein protect in vivo via Fc-γ receptor and complement-dependent effector mechanisms. J. Virol. 2011 85(22):11567-80. PMCID: PMC3209272
Szretter KJ, Brien JD, Thackray LB, Virgin HW, Cresswell P, Diamond MS. The interferon-inducible gene viperin restricts West Nile virus pathogenesis. J Virol. 2011 85(22):11557-66. PMCID: PMC3209274
Brien JD, Daffis S, Lazear HM, Cho H, Suthar MS, Gale M Jr, Diamond MS. Interferon Regulatory Factor-1 (IRF-1) Shapes Both Innate and CD8 T Cell Immune Responses against West Nile Virus Infection. PLoS Pathogens. 2011 Sep;7(9):e1002230. PMCID: PMC3164650
Purtha WE, Tedder TF, Johnson S, Bhattacharya D, and Diamond MS. Memory B cells but not long-lived plasma cells possess antigen specificities for viral escape mutants. 2011 J. Exp Med. In press.
Pinto AK, Daffis S, Brien JD, Gainey MD, Yokoyama WF, Sheehan KCF, Murphy KM, Schreiber RD, and Diamond MS. A temporal role of type I interferon signaling in CD8+ T cell maturation during acute West Nile virus infection. 2011 PLoS Pathogens. In press.

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Created at 11/10/2011 10:51 AM by DBBS_SP_SAPP
Last modified at 11/10/2011 12:30 PM by Kathryn Ruzicka