|Department Affiliations||Department of Molecular Microbiology and Immunology Department of Medicine, Infectious Diseases, Neurology|
|SOM Address||E-5132 Bloomberg School of Public Health Building|
Gwendolyn Binder-Scholl 1996 – 2002
Mayra Garcia 1999 – 2006
Patty Shish Vernon 2000 – 2004
Eunhye Park 2004 – 2009
We are studying the pathogenesis of two acute RNA viral infections: alphavirus encephalitis and measles. Encephalitis research focuses on the mechanisms of viral neurovirulence and the role of the immune response and host genes in recovery using a mouse model. Sindbis virus belongs to the alphavirus group of mosquito-borne causes of viral encephalitis. Sindbis virus causes encephalitis by replicating in and damaging neurons. Virulence is determined by a variety of viral proteins and recombinant viruses are constructed to determine the importance of changes in individual amino acids and the mechanism by which they alter virus replication in vivo and in vitro. Genetic analysis is being used to identify host genes that determine susceptibility to fatal encephalitis. Clearance of virus from neurons requires a non-cytolytic process to avoid further damage to the infected neurons. Production of antibody and interferon-gamma are the primary mechanisms by which virus is cleared but viral RNA persists and requires long-term suppression of virus reactivation with residence of antibody-secreting cells and T cells in the nervous system. The mechanisms by which intracellular virus replication is inhibited are being determined using monoclonal antibodies, immunodeficient mice and neuronal cultures. Measles is a rash disease that causes the death of >100,000 children per year and is associated with immune suppression and increased susceptibility to other infections. Vitamin A supplementation decreases measles-associated mortality. The mechanisms of immune suppression and effects of vitamin A are being studied by determining the effects on immune cell function and virus clearance. The rash is a manifestation of the cellular immune response and associated with clearance of infectious virus. However, clearance of viral RNA takes many weeks, requires the action of antiviral antibodies, as well as T cells and results in life-long protection from reinfection. The mechanisms of protective immunity and of virus clearance are investigated through the study of experimental vaccines and infected humans, monkeys and cultured cells. Human studies have been conducted primarily in Zambia where the interaction of measles and HIV infections is also of interest.
- Lin, W.H., Griffin, D.E., Rota, P.A., Papania, M. Cape, S.P., Bennett, D., Quinn, B., Sievers, R.E., Shermer, C. Powell, K., Adams, R.J., Godin, S. and Winston, S. Successful respiratory immunization with dry powder live-attenuated measles virus vaccine in rhesus macaques. Proc. Natl. Acad. Sci. USA 108:2987-2992, 2011.
- Metcalf, T.U. and Griffin, D.E. Alphavirus-induced encephalomyelitis: antibody-secreting cells and viral clearance from the nervous system. J. Virol. 85:11490-11501, 2011.
- Lin, W-H.W., Kouyos, R.D., Adams, R.J., Grenfell, B and Griffin D.E. Prolonged persistence of measles virus RNA is characteristic of primary infection dynamics. Proc. Natl. Acad. Sci. USA 109:14989-14994, 2012.
- Griffin, D.E., Lin, W.H. and Pan, C.H. Measles virus, immune control and persistence, FEMS Microbiol. Rev. 36:649-662, 2012.
- Metcalf, T.U., Baxter V.K., Nilaratanaku, V. and Griffin, D.E. Recruitment and retention of B cells in the CNS in response to alphavirus encephalomyelitis. J. Virol. 87:2420-2429, 2013.
- Lin, W-H., Vilalta, A., Adams, R.J., Rolland, A., Sullivan, S.M. and Griffin, D.E. Vaxfectin adjuvant improves antibody responses of juvenile rhesus macaques to a DNA vaccine encoding the measles virus hemagglutinin and fusion proteins. J. Virol. 87:6560-6568, 2013.
- Shivakoti, R., Siwek, M., Hauer, D., Schultz, K.W. and Griffin, D.E. Role of defective interfering RNA in the induction of dendritic cell production of type I and type III interferon by wild-type and vaccine strains of measles virus. J. Virol. 87:7816-7827, 2013.
- Lin, W-H.W., Pan, C-H, Adams, R.J., Laube, B.L. and Griffin, D.E. Vaccine-induced measles virus-specific T cells do not prevent infection or disease but facilitate subsequent clearance of viral RNA. mBio 5:e01047-14, 2014.