 Neel
K. Krishna, Ph.D.
Assistant Professor
Lewis Hall, #3184
Office: (757) 446-5677
Email: krishnnk@evms.edu
Teaching: Molecular Biology, Virology
Biomedical Sciences Program Track: Molecular
Integrative Biosciences (MIB)
Education
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B.A., Earlham College,
Richmond, IN
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Ph.D., Pennsylvania State
University School of Medicine, Hershey, PA
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Postdoctoral Training, The
Scripps Research Institute, La Jolla, CA
Research Interests
Dr. Krishna's laboratory
studies the human astroviruses (HAstVs), a family of
non-enveloped, icosahedral RNA viruses that cause
gastroenteritis, predominantly in infants. Eight HAstV
serotypes have been identified with a worldwide
distribution. While the HAstVs represent a significant
public health concern, very little is known about the
pathogenesis and host immune response to this virus. We have
demonstrated that HAstV-1 virions, specifically the viral
capsid protein, suppress the complement system, a
fundamental component of the innate immune response against
pathogens in vertebrates. This is achieved by the capsid
binding to the first component of the complement pathway,
C1q. Binding of C1q by the capsid inhibits complement
activation and its downstream effects (e.g., inflammation,
cell lysis, phagocytosis, etc.). We are interested in
determining the mechanism whereby the capsid protein
inhibits complement activation and the role of C1q binding
in the pathogenesis and life-cycle of the Astroviridae.
A second area of interest for
our laboratory is the development of the astrovirus capsid
protein as a therapeutic for complement-mediated disease.
While the human complement system represents a front-line
defense against pathogens such as bacteria and viruses, its
uncontrolled activation can lead to severe pathology in many
different inflammatory and autoimmune disorders with an
immune component such as systemic lupus erythematosis,
rheumatoid arthritis, inflammatory bowel disease,
ischemia-reperfusion injury (myocardial infarct, stroke),
glomerulonephritis, adult respiratory distress syndrome,
transplant rejection, graft versus host disease and burn
injuries. Currently there are no effective complement
inhibitors on the market. Given the very potent inhibition
of human astrovirus coat protein on the complement system,
we are currently interested in developing this protein into
a therapeutic compound as method for regulating aberrant
complement activity.
Selected Publications
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Bonaparte, R. S., P. S.
Hair, D. Banthia, D. M. Marshall, K. M. Cunnion and
N. K. Krishna. 2008. Human astrovirus coat protein
inhibits serum complement activation via C1, the first
component of the classical pathway. J. Virol,
82(2):817-827
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Krishna, N.K. 2005.
Identification of structural domains involved in
astrovirus capsid biology. Viral Immunol., 18(1):17-26.
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Venter, P.A., N.K.
Krishna and A. Schneemann. 2005. Capsid protein
synthesis from replicating RNA directs specific
packaging of the genome of a multipartite, positive
strand RNA virus. J. Virol., 79:6239-6248.
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Karabekian, Z., L.K. Hanson,
J.S. Slater,
N.K. Krishna, L.L. Bolin, J.A. Kerry and A.E.
Campbell. 2005. Complex Formation Among Murine
Cytomegalovirus US22 Proteins Encoded by M139, M140, and
M141. J. Virol., 79:3525-3535.
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Schneemann. 2003. Analysis
of RNA packaging in wild-type and mosaic protein capsids
of Flock House virus using recombinant baculovirus.
Virology, 305:10-24.
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Taylor, D.J., N.K.
Krishna, M.A. Canady, A. Schneemann and J.E.
Johnson. 2002. Large scale, pH dependent, quaternary
structure changes in a RNA virus capsid are reversible
in the absence of subunit auto-proteolysis. J. Virol.,
76:9972-9980.
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Tang, L., C.S. Lin, N.K.
Krishna, M. Yeager, A. Schneemann and J.E. Johnson.
2002. Virus-like particles of a fish nodavirus display
a capsid subunit domain organization different from that
of insect nodaviruses. J. Virol., 76:6370-6375.
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Lin, C.S., M.W. Lu, L. Tang,
W. Liu, C.B. Chao, C. J. Lin, N.K. Krishna, J.E.
Johnson and A. Schneemann. 2001. Characterization of
virus-like particles assembled in a recombinant
baculovirus system expressing the capsid protein of a
fish nodavirus. Virology, 290:50-58.
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Krishna, N.K. and J.W.
Wills. 2001. Insertion of capsid proteins from
nonenveloped viruses into the retroviral budding
pathway. J. Virol., 75:6527-6536.
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Schneemann, A., N.K.
Krishna, V. Reddy and J.E. Johnson. 1999. New
perspectives on the importance of RNA-protein
interactions in nodavirus structure and function. In:
Recent Research Developments in Virology. Pandalai, G.
(Ed.) Transworld Research Network. 1:295-315.
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Krishna, N.K. and A.
Schneemann. 1999. Formation of an RNA heterodimer upon
heating of nodaviral particles. J. Virol., 73:1699-1703.
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Bowzard, J.B., R.P. Bennett,
N.K. Krishna, S.M. Ernst, A. Rein and J.W. Wills.
1998. Importance of basic residues in the nucleocapsid
sequence for retrovirus Gag assembly and complementation
rescue. J. Virol., 72:9034-9044.
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Krishna, N.K., S.
Campbell, V.M. Vogt and J.W. Wills. 1998. Genetic
determinants of Rous sarcoma virus particle size. J.
Virol., 72:564-577.
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Xiang, Y., T.W. Ridky,
N.K. Krishna and J. Leis. 1997. Altered Rous sarcoma
virus Gag polyprotein processing and its effects on
particle formation. J. Virol., 71:2083-2091.
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Krishna, N.K., R.A.
Weldon, Jr. and J.W. Wills. 1996. Transport and
processing of the Rous sarcoma virus Gag protein in the
endoplasmic reticulum. J. Virol., 70:1570-1579.
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Pepinsky, R.B., I.A.
Papayannopoulos, E. Pingchang Chow, N.K. Krishna,
R.C. Craven and V.M. Vogt. 1995. Differential
proteolytic processing leads to multiple forms of the CA
protein in avian sarcoma and leukemia viruses. J. Virol.,
69:6430-6438.
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Parent, L.J., R.P. Bennett,
R.C. Craven, T.D. Nelle, N.K. Krishna, J.B.
Bowzard, C.B. Wilson, B.A. Puffer, R.C. Montelaro and
J.W. Wills. 1995. Positionally independent and
exchangeable late budding functions of the Rous sarcoma
virus and human immunodeficiency virus Gag proteins. J.
Virol., 69:5455-5460.
Patents
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International Patent
Application filed under the Patent Corporation Treaty,
“Nodavirus-VLPs Immunization Composition.” Provisional
application filed May 29, 2005. Applicants: Thiery R.,
Baud M., Cabon J., Cozien J., Lamour F., Lin C.S.,
Krishna N.K., Johnson J.E. and Schneemann A.
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"Methods for regulating
complement cascade proteins using astrovirus coat
protein and derivatives thereof”. Provisional
application filed 16 June, 2006. Applicants: Krishna,
N.K. and Cunnion K.M.
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