The Laboratory of Michael McVoy
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CMV Cafe:
The Laboratory of Michael McVoy |
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VIRGINIA COMMONWEALTH UNIVERSITY School of Medicine |
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RESEARCH INTERESTS
The mission of our laboratory is to improve human health by developing new tools to combat a very serious pathogen, human cytomegalovirus (HCMV). We are approaching this problem through two avenues: (I) understanding the basic mechanisms of herpesvirus genome replication and maturation, with an aim toward development of novel antiviral drugs; and (II) exploring novel approaches to vaccine design.
I. Herpesvirus DNA Maturation
A. Terminase. Herpesviruses replicate their DNA in the form of concatemers - long DNA molecules comprised of many viral genomes linked together in a "daisy chain" like structure. The genome on the end is “packaged” into a preformed capsid, but must then be liberated from the concatemer by a precise cut of the DNA. Both the packaging and the cleavage of the DNA are mediated by an enzymatic complex called terminase. Because normal cells do not package or cleave DNA, this process is an attractive target for development of new antivirals. In collaboration with Deborah Parris at Ohio State, we are currently focused on expression and purification of terminase subunits and their biochemical evaluation in vitro.
B. Alkaline Nuclease. While genetic studies suggest this protein is critically important for HCMV replication, its function remains a mystery. Through in silico modeling, mutagenesis, and recombinant protein expression, we have identified critical amino acids required for enzymatic activity. Current efforts are focused on insertion of these mutations into the viral genome to evaluate their impact on viral replication.
II. Novel Approaches to HCMV Vaccines
A. The guinea pig cytomegalovirus (GPCMV) vaccine model. GPCMV is the only small animal CMV that causes fetal infection and pathogenesis. In collaboration with Mark Schleiss and Alistair McGregor at the University of Minnesota, we have worked to develop molecular and immunological tools to expand the utility of this model. The complete genome has been sequenced and a number of potential immune evasion genes identified. In particular, three genes encoding MHC class I homologs appear to be NK evasins. An infectious BAC clone was also constructed. Current projects will define the role of MHC I homologs and their potential to augment live or disabled vaccines.
B. Antibodies that neutralize epithelial entry. The ability to elicit potent neutralizing antibody responses may be critical for a successful HCMV vaccine. We recently showed that two experimental vaccines, the Towne live attenuated vaccine and the subunit gB/MF59 vaccine, perform poorly, compared to natural infection, with respect to inducing neutralizing antibodies that block epithelial cell entry. Evidence suggests that epitopes crucial for inducing such activity lie within the gH/gL/UL128-131 complex. Current studies are focused on characterizing humoral responces to this complex and identifying vaccine strategies to induce them. Strategies of interest include DNA vaccines, subunit proteins, and live attenuated, disabled, or inactivated whole virus-based approaches.
Mailing Address:
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Michael A. McVoy
Department of Pediatrics
Division of Pediatric Infectious Diseases
Virginia Commonwealth University School of Medicine
P.O. Box 980163 MCV Station
Richmond VA 23298-0163
office phone:
804-828-1739
lab phone: 804-828-2291
division secretary: 804-828-0132
fax: 804-828-6455
e-mail: mmcvoy@vcu.edu
Federal
Express Address:
Michael McVoy
Sanger Hall Room 12-026
1101 East Marshall Street
Richmond VA 23298
Jianben Wang, M.D.
Research Associate (1996)
M.D.
Harbin Medical Institute, Harbin P.R. China
M.S. Shanxi Medical Institute,
Taiyuan P.R. China
Anne Sauer, Ph.D.
Post-doctoral fellow (2003)
Ph.D. Virginia Commonwealth University School of Medicine
B.S. University of Alabama (Physical
Education, Health, and Recreation)
B.S. Virginia Commonwealth University
(Biology)
Frances Saccoccio
M.D/Ph.D. student, Department of Microbiology & Immunology
(2009 - )
B.S. Worcester Polytechnic Institute (2003)
Sabrina Prescott
Ph.D. student, Molecular
Biology and Genetics
(20010 - )
B.S. University of Massachusetts (1993)
Sukhada Bhave
M.S. student, Molecular
Biology and Genetics
(2011 - )
Bachelor of Pharmacy University of Mumbai (2010)
Megan Reeves-Crumpler, Ph.D.
Ph.D. Student, Department of Microbiology & Immunology (2004-2008)
B.S. University of Florida (2002)
Ph.D. Virginia
Commonwealth University School of Medicine
Ben
Meza
M.S. Student, Department
of
Physiology
(2007-2008)
Certificate in Biochemistry, Virginia
Commonwealth University (2007)
B.A. Davidson
College (2006)
Juan
Lacayo, Ph.D.
Ph.D.
student, Department of Microbiology & Immunology (1999-2003)
B.S.
Virginia Commonwealth University
Ph.D. Virginia
Commonwealth University School of Medicine
Erin Douglass, M.D.
Laboratory Specialist (2003-2004)
B.S. Duke University (2003)
M.D. Medical College of Virginia class of 2008
Cristine Howard, M.D.
Laboratory Specialist
(2001-2003)
B.S.
College of William and Mary
M.S.
College of William and Mary
M.D.
Medical College of Virginia class of 2007
Melissa
Mondello, M.D.
Laboratory Specialist (2002-2003)
B.S. University of Richmond
M.D. Medical College of Virginia class
of 2007
Will
Bierach
M.S.
Student (2001-2002)
B.S. Campbell University
Carlos Berbes
Ph.D. student, Department of Microbiology & Immunology (1998-2001)
B.S. Virginia Commonwealth University
M.S. Medical College of Virginia Campus of Virginia Commonwealth
University
Frederic Schynts, Ph.D.
Visiting Ph.D. student from the University of
Liege, Belgium (2001 – 2002)
Ph.D. University of Liege, Belgium.
Currently: Head of Molecular analytics
GSKbiologicals, Rixensart Belgium
Stephanie Siegmund
Field Experience Student (2005 - 2006)
Governor's School for Government and
International Studies
Jessica Abbate
Field Experience Student (1998 - 1999)
Governor's School for Government and
International Studies
B.S. The University of Virginia (2003)
Dipti Ramnarain
Field Experience Student (1998 - 1999)
Governor's School for Government and
International Studies
B.S. The College of William and Mary
(2003)
Yulin Liu
Visiting Scientist (2000 - 2001)
M.D. Xinjiang Medical University,
Urumuqi P.R. China
B.S. Xinjiang Medical University,
Urumuqi P.R. China
Jae Kyun Hur
Visiting Scientist (1996 - 1997)
M.D. Catholic Medical College, Seoul Korea
Ph.D. Catholic Medical College, Seoul Korea
Anupam Bapu Jena
(1995 - 1996)
Governor's School for Government
and International Studies
B.S. Massachusetts Institute of Technology
McVoy, M. and S.P. Adler.
1991. Analysis of human cytomegalovirus DNA replicative intermediates:
DNA forms not predicted by the rolling circle model. In M.P
Landini (ed.), Progress in cytomegalovirus research. Elsevier Science
Publishers, Amsterdam
Abstract
Brown, J. C. , M. A.
McVoy and F. L. Homa. 2002. Packaging DNA into
Herpesvirus Capsids. In A. Holzenburg and E. Bogner
(ed.), Structure-Function Relationships of Human Pathogenic
Viruses. Kluwer Academic/Plenum Publishers, London. Abstract
Schynts, F., F. Meurens, B. Muylkens, A. L. Epstein, M. McVoy, and E. Thiry. 2002. Réplication, clivage-encapsidation et recombinaison de I’ADN des herpèsvirus. Virologie 6:353-52. Abstract
Schleiss, M. R. and M. A. McVoy.
2004. Overview of congenitally and perinatally acquired
cytomegalovirus infections: recent advances in antiviral therapy.
Expert Review of Anti-infective Therapy, 2:89-103.
Selected Journal Publications
McVoy, M. and S.P. Adler. 1994. Human cytomegalovirus DNA replicates after early circularization by concatemer formation and inversion occurs within the concatemer. Journal of Virology, 68:1040-1051
McVoy, M.A., Nixon, D.E., and
S.P. Adler. 1997. Circularization and cleavage of guinea
pig cytomegalovirus genomes.
Journal of Virology, 71:4209-4217
McVoy, M.A., Nixon, D.E.,
Adler, S.P., and E.S. Mocarski. 1997. Sequences within the
herpesvirus-conserved pac1 and pac2 motifs are required
for cleavage and packaging of the murine cytomegalovirus genome.
Journal of Virology, 72:48-56
McVoy, M.A. and E.S. Mocarski. 1999. Tetracycline regulation of
reporter gene expression within the human cytomegalovirus genome.
Virology 258:295-303.
McVoy, Michael A., Daniel E. Nixon, Jay K. Hur, and Stuart P. Adler. 2000. The ends on herpesvirus DNA replicative concatemers contain pac2 cis cleavage/packaging elements and their formation is controlled by terminal cis sequences. Journal of Virology, 74:1587-1592.
McVoy, M.A. and D. Ramnarain. 2000. The machinery to support genome segment inversion exists in a herpesvirus which does not naturally contain invertible elements. Journal of Virology, 74:4882-7.
Abbate, J., J. C. Lacayo, M. Prichard, G. Pari, and M. A. McVoy. 2001. A bifunctional protein conferring enhanced green fluorescence and puromycin resistance. BioTechniques, 31: 340-347.
Nixon, D. E. and M. A. McVoy. 2002. Terminally repeated sequences on a herpesvirus genome are deleted following circularization but are reconstituted by duplication during cleavage and packaging of concatemeric DNA. Journal of Virology, 76:2009-2013.
DeWire, S., M. A.
McVoy and
B. Damania. 2002. Kinetics of expression of rhesus monkey
rhadinovirus
(RRV) and characterization of a polycistronic transcript encoding RRV
Orf50/Rta,
RRV R8, and R8.1 genes. Journal of Virology, 76:9819-9831.
Mark R. Schleiss, David I.
Bernstein, Michael A. McVoy, Greg Stroup, Fernando Bravo, Blaine
Creasy, Alistair McGregor, Kristin Henninger, and Sabine Hallenberger.
2005. The Nonnucleoside Antiviral, BAY 38-4766, Protects Against
Cytomegalovirus Disease and Mortality in Immunocompromised Guinea
Pigs. Antiviral Research, 65:35-43.
Michael A. McVoy and Daniel E. Nixon.
2005. The Impact of BDCRB
(2-Bromo-5,6-Dichloro-1-_-D-Ribofuranosyl Benzimidazole Riboside) and
Inhibitors of DNA, RNA, and Protein Synthesis on Human Cytomegalovirus
genome maturation. Journal of Virology, 79:11115-11127.
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Date Last Modified: April 2011
