CMV Cafe: 
The Laboratory of Michael McVoy
 
VIRGINIA COMMONWEALTH UNIVERSITY
School of Medicine
 
Research Interests
How to Contact Us
Lab Members
 

Publications


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 responses 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. 



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      Mailing Address:
                                                      
      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
 

Current Lab Members 

Michael A. McVoy, Ph.D.
      Professor
      Department of Pediatrics and Microbiology & Immunology
      B.S. College of William and Mary
      Ph.D. Medical College of Virginia/Virginia Commonwealth University
     
Jianben Wang, M.D.
      Research Associate
      M.D. Harbin Medical Institute, Harbin P.R. China
      M.S. Shanxi Medical Institute, Taiyuan P.R. China

Xiaohong Cui, M.D., Ph.D.
      Research Associate
      Ph.D. Second Military Medical University, Shanghai, China
      M.S. Third Military Medical University, Chongqing, China
      M.D. Third Military Medical University, Chongqing, China

Ronzo Lee, B.S.
      Laboratory Specialist Senior
      B.S. Virginia Commonwealth University, Richmond VA

Anne Sauer, Ph.D.
      Post-doctoral fellow
      Ph.D. Virginia Commonwealth University School of Medicine
      B.S. University of Alabama (Physical Education, Health, and Recreation)
      B.S. Virginia Commonwealth University (Biology) 

Zainab Almahdi, Ph.D.
      Post-doctoral fellow
      Instructor, College of Science for Women, Babylon University, Babylon Iraq
      Ph.D. University of Babylon, College of Science (2011)

Ying Qi, Ph.D. M.D., Ph.D.
      Post-doctoral fellow
      M.D., Ph.D. China Medical University (2007)

Sabrina Prescott, B.S.
      Ph.D. student,  Molecular Biology and Genetics (2010 - )
      B.S. University of Massachusetts (1993)


Former Lab Members

Zohaib Alam
      M.S. student, Department of Microbiology & Immunology (2009 - 2012)
      B.S. Virginia Commonwealth University (2009)

Sukhada Bhave
      M.S. student,  Molecular Biology and Genetics (2011 - 2012)
      Bachelor of Pharmacy University of Mumbai (2010)     

Frances Saccoccio
      M.D/Ph.D. student,  Department of Microbiology & Immunology (2009 - 2012)
      B.S. Worcester Polytechnic Institute (2003)      

EL-Sayed E. Habib, Ph.D.
       Visiting Scientist (2009)
       Associate Professor, Department of Microbiology, Mansoura University, Egypt     

Alison Kuchta, M.D., Ph.D
      M.D/Ph.D. student,  Molecular Biology and Genetics (2004-2008)
      B.S. Virginia Commonwealth University (2002)
      M.D./Ph.D.  Virginia Commonwealth University School of Medicine

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)

Stephen Dollery, Ph.D.
      Laboratory Specialist (2003-2006) 
      B.Sc. Sheffield Hallam University  (2003)
      Ph.D. Virginia Commonwealth University School of Medicine

Aveena  Kochar
      Summer Research Intern (2006)
      College of William & Mary  

Daniel E. Nixon, D.O., Ph.D.
      Ph.D. student, Molecular Biology and Genetics Program (1995-2005)
      B.S. Ohio State University
      D.O. Ohio University
      Currently: Associate Professor, Virginia Commonwealth University School of Medicine

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




Book Chapters and Reviews

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

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.

 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.

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.

 McGregor, A., M. A. McVoy, and M. R. Schleiss.  2012.  The Guinea Pig Model of Congenital Cytomegalovirus Infection.  In M. J. Reddehase (ed.), Cytomegaloviruses: From Molecular Pathogenesis to Intervention.  Caister Academic Press, Norwich.




Selected Journal Publications


1.  Adler, S. P., M. McVoy, V. G. Biro, W. J. Britt, P. Hider, and D. Marshall.  1985.  The detection of antibody against cytomegalovirus using latex agglutination.  Journal of Clinical Microbiology, 22:68-70.  PMC268323  Free PMC Article

2.  Adler, S. P., J. Baggett, and M. McVoy.  1985.  Transfusion associated cytomegalovirus infection among seropositive cardiac surgery patients.  Lancet, 2:743-746.  PMID: 2864484

 

3.  Adler, S. P., J. Baggett, M. Wilson, L. Lawrence, and M. McVoy.  1986.  Molecular epidemiology of cytomegalovirus transmission in a nursery: lack of evidence for nosocomial transmission.  Journal of Pediatrics, 108:117-123.  PMID: 3003315

 

4.  Adler, S., and M. McVoy.  1986.  Detection of cytomegalovirus antibody by enzyme immunoassay and lack of evidence for an effect resulting from strain heterogeneity.  Journal of Clinical Microbiology, 24:870-872.  PMC269049  Free PMC Article

 

5.  Adler, S. P. and M. A. McVoy.  1989.  Cytomegalovirus infections in seropositive patients after transfusion: the effect of red cell storage and volume.  Transfusion, 29:667-71.  PMID: 2552625

 

6.   McVoy, M. A. and S. P. Adler.  1989.  Immunologic evidence for frequent age related cytomegalovirus reactivation in seropositive immunocompetent individuals.  Journal of Infectious Diseases, 160:1-10.  PMID: 2543705

 

7.  Adler, S. P., M. McVoy, S. Chou, S. Hempfling, K. Yamanishi, and W. Britt.  1993.  Antibodies induced by a primary cytomegalovirus infection react with human herpesvirus 6 proteins.  Journal of Infectious Diseases, 168:1119-1126.  PMID: 8228344

 

8.  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.  PMC236542  Free PMC Article

 

9.  Adler, S. P., K. V. Shaw, M. McVoy, R. L. Burke, and H. Liu.  1995.  Guinea pig and human cytomegaloviruses do not share cross-reactive neutralizing epitopes.  Journal of Medical Virology, 47:48-51.  PMID: 8551258

 

10. McVoy, M. A., D. E. Nixon, and S. P. Adler.  1997.  Circularization and cleavage of guinea pig cytomegalovirus genomes.  Journal of Virology 71:4209-4217.  PMC191635  Free PMC Article

 

11.  McVoy, M. A., D. E. Nixon, S. P. Adler, and E. S. Mocarski.  1998.  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.  PMC109348  Free PMC Article

 

12.  McVoy, M. A. and E. S. Mocarski.  1999.  Tetracycline-mediated regulation of gene expression within the human cytomegalovirus genome.  Virology, 258: 295-303.  PMID: 10366566

 

13.   McVoy, M. A., D.E. Nixon, J. K. Hur, and S. 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.  PMC111498  Free PMC Article

 

14.  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.  PMC112012  Free PMC Article

 

15.  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.  PMID: 11515370

 

16.  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, 76:2009-13. PMC135902  Free PMC Article

 

17.  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.  PMC136498  Free PMC Article

 

18.  Hahn, G., M. Jarosch, J. B. Wang, C. Berbes and M. A. McVoy.  2003.  Tn7-mediated introduction of DNA sequences into bacmid-cloned cytomegalovirus genomes for rapid recombinant virus construction.  Journal of Virological Methods, 107:185-194.  PMID: 12505633

 

19.  Lacayo, J.  H. Sato, H. Kamiya, and M. A. McVoy.  2003. Down-regulation of surface major histocompatibility complex class I by guinea pig cytomegalovirus.  Journal of General Virology, 84:1-7.  PMID: 12533702

 

20.  Hahn, G., M. Wagner, D. Rose, S. Rhiel, and M. A. McVoy. 2003.  Cloning of the genomes of Human Cytomegalovirus strains Toledo, TownevarRIT3 and Townelong as BACs and site-directed mutagenesis using a PCR-based technique.  Virology, 307:164-177.  PMID: 12667824

 

21.  Schynts, F., M. A. McVoy, F. Meurens, B. Detry, A. L. Epstein, and E. Thiry.  2003. The structures of bovine herpesvirus 1 virion and concatemeric DNA: implications for cleavage and packaging of herpesvirus genomes.  Virology, 314:326-335.  PMID: 14517085

 

22.  Nixon, D. E.  and M. A. McVoy.  2004.  Dramatic effects of BDCRB (2-bromo-5,6-Dichloro-1-b-D-ribofuranosyl benzimidazole riboside) on the genome structure, packaging, and egress of guinea pig cytomegalovirus. Journal of Virology, 78:1623-1635.  PMC369448  Free PMC Article

 

23.  Schleiss, M. R., D. I. Bernstein, M. A. McVoy, G. Stroup, F. Bravo, B. Creasy, A. McGregor, K. Henninger, and S. Hallenberger. 2005. The Nonnucleoside Antiviral, BAY 38-4766, Protects Against Cytomegalovirus Disease and Mortality in Immunocompromised Guinea Pigs.  Antiviral Research, 65:35-43.  PMC2768478  Free PMC Article

 

24.  McVoy, M. A. and Daniel E. Nixon.  2005.  The Impact of BDCRB (2-Bromo-5,6-Dichloro-1-b-D-Ribofuranosyl Benzimidazole Riboside) and Inhibitors of DNA, RNA, and Protein Synthesis on Human Cytomegalovirus genome maturation. Journal of Virology, 79:11115-11127.  PMC1193602  Free PMC Article

 

25.  Dighe, A., M. Rodriguez, P. Sabastian, X. Xie, M. McVoy, and M. G. Brown.  2005.  Requisite H2k role in NK cell-mediated resistance in acute murine CMV infected MA/My mice.  Journal of Immunology, 175:6820-8.  PMID: 16272339

 

26.  Wang, J. B., D. E. Nixon, and M. A. McVoy.  2008.  Definition of the minimal cis-acting sequences necessary for genome maturation of a herpesvirus, murine cytomegalovirus.  Journal of Virology, 82:2394-404.  PMC2258947  Free PMC Article

 

27.  Cui, X., A. McGregor, M. R. Schleiss, M. A. McVoy.  2008.  Cloning the complete guinea pig cytomegalovirus genome as an infectious bacterial artificial chromosome with excisable origin of replication. Journal of Virological Methods, 149: 231-9.  PMC2831993  Free PMC Article

 

28.  McGregor, A., K. Y. Choi,  G. Stroup, X. Cui, M. A. McVoy, M. R. Schleiss.  2008. Expression of the Human Cytomegalovirus UL97 Gene in a Chimeric Guinea Pig Cytomegalovirus (GPCMV) Results in Viable Virus with Increased Susceptibility to Ganciclovir and Maribavir.  Antiviral Research, 78: 250-9.  PMC2787096  Free PMC Article

 

29.  Wang, J. B. and M. A. McVoy.  2008. Mutagenesis of the murine cytomegalovirus M56 terminase gene.  Journal of General Virology, 89:2864-2868.  PMID: 18931084 Free full text

 

30.  Cui, X., B. P. Meza, S. P. Adler, and M. A. McVoy. 2008. Cytomegalovirus vaccines fail to induce epithelial entry neutralizing antibodies comparable to natural infection. Vaccine, 26:5760-5766.  PMC2583261  Free PMC Article

 

31.  Schleiss, M. R., A. McGregor, K. Y. Choi, S. V. Date, X. Cui, and M. A. McVoy. 2008. Analysis of the Nucleotide Sequence of the Guinea Pig Cytomegalovirus Genome. Virology Journal, 5:139.  PMC2614972  Free PMC Article

 

32.  Cui, X., A. McGregor, M. R. Schleiss, and M. A. McVoy. 2009. The Impact of Genome Length on Replication and Genome Stability of the Herpesvirus Guinea Pig Cytomegalovirus.  Virology, 386:132-8.  PMC2693885  Free PMC Article

 

33.  Crumpler, M. M., Y. Choi, M. A. McVoy, and M. R. Schleiss. 2009. A live guinea pig cytomegalovirus vaccine deleted of three putative immune evasion genes is highly attenuated but remains immunogenic in a vaccine/challenge model of congenital cytomegalovirus infection.  Vaccine, 27:4209-18.  PMID: 19389443

 

34.  Schleiss, M. R. and M. A. McVoy.  2010.  Guinea Pig Cytomegalovirus: A Model for the Study of the Prevention and Treatment of Maternal-Fetal Transmission.  Future Virology, 5:207-17. 

 

35.  Sauer, A., J. B. Wang, G. Hahn., and M. A. McVoy. 2010. A Human Cytomegalovirus Deleted of Internal Repeats Replicates with Near Wild Type Efficiency but Fails to Undergo Genome Isomerization.  Virology, 401:90-5.  PMC2849842  Free PMC Article

 

36.  Saccoccio, F., A. Sauer, X. Cui, A. Armstrong, E. E. Habib, D. Johnson, B. Ryckman, A. Klingelhutz, S. P. Adler, and M. A. McVoy.  2011.  Peptides from Cytomegalovirus UL130 and UL131 Proteins induce high titer antibodies that block viral Entry into Mucosal Epithelial Cells.  Vaccine, 29:2705-11. PMC3084484  Free PMC Article

 

37.  Olejniczak, Megan J., K. Y. Choi, M. A. McVoy, X. Cui and M. R. Schleiss. 2011. Intravaginal cytomegalovirus (CMV) challenge elicits maternal viremia and results in congenital transmission in a guinea pig model. Virology Journal, 8:89. PMC3062623  Free PMC Article

 

38.  Wang, J. B. and M. A. McVoy. 2011. A 128-bp sequence containing pac1 and a presumed cryptic pac2 includes the cis elements sufficient to mediate efficient genome maturation of human cytomegalovirus. Journal of Virology, 85:4432-9. PMC3126264  Free PMC Article


39.  Saccoccio, F. M., M. K. Gallagher, S. P. Adler, and M. A. McVoy. 2011. Neutralizing Activity of Saliva against Cytomegalovirus. Clinical and Vaccine Immunology, 18:1536-1542. PMC3165217  Free PMC Article

 

40.  Kuchta, A. L., H. Parikh, Y. Zhu, G. E. Kellogg, D. S. Parris, and M. A. McVoy. 2012. Structural modelling and mutagenesis of human cytomegalovirus alkaline nuclease UL98. The Journal of General Virology 93:130-138. PMC3352332  Free PMC Article

 

41.  Cui, X., S. P. Adler, A. J. Davison, L. Smith, S. E. Habib el, and M. A. McVoy. 2012. Bacterial artificial chromosome clones of viruses comprising the towne cytomegalovirus vaccine. J Biomed Biotechnol 2012:428498. PMC3236503  Free PMC Article

 

42.  Wang, J. B., Y. Zhu, M. A. McVoy, and D. S. Parris. 2013. Changes in subcellular localization reveal interactions between human cytomegalovirus terminase subunits.  Virology Journal, 9:315. PMID: 23259714  Free full text

 

43.  Yang, D., K. Tamburro, D. Dittmer, X. Cui, M. McVoy, N. Hernandez, and M. Schleiss.  2013.  Complete Genome Sequence of Pathogenic Guinea Pig Cytomegalovirus from Salivary Gland Homogenate of Infected Animals.  Genome Announcements, 1:1. PMID: 23516193  Free PMC Article

 

44.  Cui, X., R. Lee, S. P. Adler, and M. A. McVoy. 2013. Antibody inhibition of human cytomegalovirus spread in epithelial cell cultures. J Virol Meth, 192:44-50 PMID: 23669101

 

45.  Bhave, S., H. Elford, and M. A. McVoy. 2013. Ribonucleotide reductase inhibitors hydroxyurea, didox, and trimidox inhibit human cytomegalovirus replication in vitro and synergize with ganciclovir.  Antiviral Research, in press.

            Date Last Modified: August 2013