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Diane
E.
Griffin
,
MD

Professor

Diane Griffin, PhD, MD, studies how viruses cause disease and how immunity leads to both recovery and protection from re-infection.

Contact Info

615 N. Wolfe Street, Room E5636
Baltimore
Maryland
21205
US        
410-955-0105

Research Interests

Molecular Microbiology and Immunology; measles viral encephalitis vaccines arboviruses alphaviruses Sindbis virus chikungunya virus immune response
Experiences & Accomplishments
Education
MD
Stanford University
1968
PhD
Stanford University
1970
BA
Augustana College
1958
Overview
Alphaviruses and acute encephalitis ¡X Alphaviruses are transmitted by mosquitoes and cause encephalitis in mammals and birds. We study Sindbis virus, an alphavirus that causes encephalomyelitis in mice and chikungunya virus that causes rash and arthritis as well as encephalitis. The outcome of infection is determined by the virulence of the virus, age at the time of infection, genetic background and the immune response. Sindbis virus infects neurons in the brain and spinal cord and causes death of neurons and fatal disease in young animals but not in older animals. Mature neurons are protected from induction of cell death and become persistently infected. More virulent strains of Sindbis virus kill mature neurons through improved virus replication and by inducing an pathologic immune response. Virulence is determined by sequences in both structural and nonstructural genes. In nonfatal disease, antibody in combination wth interferon-gamma are primary noncytolytic mechanisms by which virus is cleared from the nervous system. Clearance of infectious virus occurs within 7-8 days without harming the infected cells.  However, it takes several weeks to decrease the levels of viral RNA to a low persistent level. We are determining the mechanisms of virulence and of noncytolytic clearance of virus and viral RNA.
Measles virus, immune response, and vaccines ¡X Measles is an important cause of childhood morbidity and mortality, partly due to increased susceptibility to other infections caused by virus-induced immune suppression. Monocytes, lymphocytes, epithelial cells and endothelial cells are infected during measles.  Infectious virus is cleared during the rash phase of illness, but viral RNA is cleared slowly over months. We are studying the effect of the immune response on clearance of measles virus and RNA in infected humans and rhesus macaques.  We are also studying the immune response to a variety of measles vaccines delivered both parenterally and by aerosol to identify the determinants of protective immunity and the mechanisms for establishing life-long immunity.
Honors & Awards
American Academy of Microbiology
National Academy of Sciences
National Academy of Medicine
Maryland Women's Hall of Fame
Pioneer Award, International Society for Neurovirology
Rudolf Virchow Medal, University of Wurzburg
Wallace Sterling Lifetime Alumni Achievement Award, Stanford University
Gilman Scholar, Johns Hopkins University
FASEB Excellence in Science Award
Association of American Physicians
Maxwell Finland Award, National Foundation for Infectious Diseases
MilliporeSigma Alice C. Evans Award, American Society for Microbiology
American Philosophical Society
Select Publications
Recent publications
  • Abraham, R., McPherson, R.L., Leung, A. K-L. and Griffin, D.E. Both ADP ribosyl binding and hydrolase activities of the alphavirus nsP3 macrodomain affect neurovirulence in mice. mBio 11:e03253, 2020.
  • Nelson, A.N., Putnam, N., Mangus, L., Lin, W-H.W., Shivakoti, R., Adams, R.J., Hauer, D., Baxter, V.K. and Griffin, D.E. Persistence of wild-type measles virus RNA is associated with long-term humoral immunity in rhesus macaques. JCI Insight 5:e134552, 2020.
  • Lin, W-H.W., Moran, E., Adams, R.J., Sievers R.E., Hauer, D., Godin, S. and Griffin, D.E. Protective immune responses to wild type measles virus reflect replication in lymphoid tissue, hematogenous spread and RNA persistence. Science Transl. Med. 12:eaax7799, 2020.
  • Yeh, J.X., Schultz, K.L.W., Calvert, V., Petricoin, E.F. and Griffin, D.E, The NF-?B/leukemia inhibitory factor/STAT3 signaling pathway in antibody-mediated suppression of Sindbis virus replication in neurons. Proc. Natl. Acad. Sci. USA 117:29035-29045, 2020.
  • Lin, W-H W., Tsay, A.J., Lalime, E.N., Pekosz, A. and Griffin, D.E. Primary differentiated respiratory epithelial cells respond to apical measles virus infection by shedding multinucleated giant cells. Proc. Natl. Acad. Sci. USA 118:e2013264118, 2021.
Projects
Immune Reconstitution Of HIV-1 Infected Zambian Children Initiating Antiretroviral Therapy