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Brian Ward

TitleAssociate Professor
InstitutionSchool of Medicine and Dentistry
DepartmentMicrobiology and Immunology
AddressUniversity of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 672
Rochester NY 14642
 
 Awards And Honors
1991 - 1992Howard Hughes Undergraduate Research Fellowship  | Indiana University
1991 - 1992High Scholastic Achievement  | Indiana University
1994     Francis M. and Harlie M. Clark Research Grant  | University of Illinois
1998 - 2003Intramural Research Training Assistant Postdoctoral Fellowship  | NIH
2001     Finalist - Norman P. Salzman Memorial Award In Virology  | NIH
2001     Fellows Award For Research Excellence  | NIH
2002     Finalist - Norman P. Salzman Memorial Award In Virology  | NIH
2002     Fellows Award For Research Excellence  | NIH
2003     Fellows Award For Research Excellence  | NIH
2005     Who's Who in Medical Science Educatio  | AcademicKeys
 
 Overview
Research Focus
Molecular Mechanisms of Poxvirus Envelope Formation
Research Overview
The Poxviridae family includes some of the largest DNA viruses known. While variola (the causative agent of smallpox) remains the most deadly member of the family, several other members, including monkeypox, tanapox, cowpox, vaccinia, Yaba-like disease virus and molluscum contagiosum, are capable of causing disease in humans. Orthopoxviruses, which include variola, monkeypox and vaccinia, have a double stranded genome of about 200 kb and are predicted to encode for approximately 200 functional open reading frames making them some the most complex animal viruses known. This complexity is best demonstrated during viral morphogenesis that results in a virion that is predicted to incorporate approximately 100 viral polypeptides and several morphologically distinct forms. Viral replication occurs entirely in the cytoplasm in discrete areas know as viral factories and results in the first infectious form termed intracellular mature virions (IMV). A subset of IMV receives an extra double membrane wrapping derived from the trans-Golgi or endosomal cisternae and are referred to as intracellular enveloped virions (IEV). After wrapping, IEV are transported via microtubules to the cell periphery where the outer membrane of the IEV fuses with the plasma membrane depositing one of the newly acquired membranes into the plasma membrane and releasing the enveloped virion from the cell. Many enveloped virions remain attached to the plasma membrane and are termed cell-associated-virus (CEV). Viral proteins deposited into the plasma membrane, by the fusion of IEV at the plasma membrane, direct the polymerization of actin on the cytosolic side forming what are called actin tails, which serve to propel CEV away from the cell and towards adjacent cells. CEV released from the plasma membrane are termed extracellular enveloped virus (EEV). IEV, CEV and EEV make up the enveloped form of vaccinia virus and IMV are considered unenveloped. While IMV represents the majority of progeny virions they are not released from the cell making the enveloped form responsible for cell-to-cell spread. Presently only seven viral proteins have been found to be specific to the enveloped form, and of these seven only six have been shown to be required for efficient envelope virus production. The major focus of my laboratory is the study of poxvirus morphogenesis, emphasizing the intracellular envelopment process. We employ molecular virological techniques along with state of the art live video microscopy and cell biology to study viral egress with the goal of understanding the molecular mechanism employed by poxviruses to produce intracellular enveloped virions. Furthermore, our research should provide insight into such cellular processes as protein trafficking, membrane and vesicle formation and intracellular trafficking.

 
 Selected Publications
List All   |   Timeline
  1. Baker JL, Ward BM. Development and comparison of a quantitative TaqMan-MGB real-time PCR assay to three other methods of quantifying vaccinia virions. J Virol Methods. 2014 Feb; 196:126-32.
    View in: PubMed
  2. Hollenbaugh JA, Gee P, Baker J, Daly MB, Amie SM, Tate J, Kasai N, Kanemura Y, Kim DH, Ward BM, Koyanagi Y, Kim B. Host Factor SAMHD1 Restricts DNA Viruses in Non-Dividing Myeloid Cells. PLoS Pathog. 2013 Jun; 9(6):e1003481.
    View in: PubMed
  3. Chan WM, Ward BM. The A33-dependent incorporation of B5 into extracellular enveloped vaccinia virions is mediated through an interaction between their lumenal domains. J Virol. 2012 Aug; 86(15):8210-20.
    View in: PubMed
  4. Chan WM, Ward BM. Increased interaction between vaccinia virus proteins A33 and B5 is detrimental to infectious extracellular enveloped virion production. J Virol. 2012 Aug; 86(15):8232-44.
    View in: PubMed
  5. Chen G, Ward BM, Yu KH, Chinchar VG, Robert J. Improved knockout methodology reveals that frog virus 3 mutants lacking either the 18K immediate-early gene or the truncated vIF-2alpha gene are defective for replication and growth in vivo. J Virol. 2011 Nov; 85(21):11131-8.
    View in: PubMed
  6. Ward BM. The taking of the cytoskeleton one two three: how viruses utilize the cytoskeleton during egress. Virology. 2011 Mar 15; 411(2):244-50.
    View in: PubMed
  7. Chan WM, Kalkanoglu AE, Ward BM. The inability of vaccinia virus A33R protein to form intermolecular disulfide-bonded homodimers does not affect the production of infectious extracellular virus. Virology. 2010 Dec 5; 408(1):109-18.
    View in: PubMed
  8. Chan WM, Ward BM. There is an A33-dependent mechanism for the incorporation of B5-GFP into vaccinia virus extracellular enveloped virions. Virology. 2010 Jun 20; 402(1):83-93.
    View in: PubMed
  9. Lee HY, Topham DJ, Park SY, Hollenbaugh J, Treanor J, Mosmann TR, Jin X, Ward BM, Miao H, Holden-Wiltse J, Perelson AS, Zand M, Wu H. Simulation and prediction of the adaptive immune response to influenza A virus infection. J Virol. 2009 Jul; 83(14):7151-65.
    View in: PubMed
  10. Ward BM. Using fluorescent proteins to study poxvirus morphogenesis. Methods Mol Biol. 2009; 515:1-11.
    View in: PubMed
  11. Johnston SC, Ward BM. Vaccinia virus protein F12 associates with intracellular enveloped virions through an interaction with A36. J Virol. 2009 Feb; 83(4):1708-17.
    View in: PubMed
  12. Earley AK, Chan WM, Ward BM. The vaccinia virus B5 protein requires A34 for efficient intracellular trafficking from the endoplasmic reticulum to the site of wrapping and incorporation into progeny virions. J Virol. 2008 Mar; 82(5):2161-9.
    View in: PubMed
  13. Ward BM. The longest micron; transporting poxviruses out of the cell. Cell Microbiol. 2005 Nov; 7(11):1531-8.
    View in: PubMed
  14. Ward BM. Visualization and characterization of the intracellular movement of vaccinia virus intracellular mature virions. J Virol. 2005 Apr; 79(8):4755-63.
    View in: PubMed
  15. Senkevich TG, Ward BM, Moss B. Vaccinia virus A28L gene encodes an essential protein component of the virion membrane with intramolecular disulfide bonds formed by the viral cytoplasmic redox pathway. J Virol. 2004 Mar; 78(5):2348-56.
    View in: PubMed
  16. Senkevich TG, Ward BM, Moss B. Vaccinia virus entry into cells is dependent on a virion surface protein encoded by the A28L gene. J Virol. 2004 Mar; 78(5):2357-66.
    View in: PubMed
  17. Ward BM, Moss B. Vaccinia virus A36R membrane protein provides a direct link between intracellular enveloped virions and the microtubule motor kinesin. J Virol. 2004 Mar; 78(5):2486-93.
    View in: PubMed
  18. Ward BM. Pox, dyes, and videotape: making movies of GFP-labeled vaccinia virus. Methods Mol Biol. 2004; 269:205-18.
    View in: PubMed
  19. Katz E, Ward BM, Weisberg AS, Moss B. Mutations in the vaccinia virus A33R and B5R envelope proteins that enhance release of extracellular virions and eliminate formation of actin-containing microvilli without preventing tyrosine phosphorylation of the A36R protein. J Virol. 2003 Nov; 77(22):12266-75.
    View in: PubMed
  20. Ward BM, Weisberg AS, Moss B. Mapping and functional analysis of interaction sites within the cytoplasmic domains of the vaccinia virus A33R and A36R envelope proteins. J Virol. 2003 Apr; 77(7):4113-26.
    View in: PubMed
  21. Ward BM, Moss B. Vaccinia virus intracellular movement is associated with microtubules and independent of actin tails. J Virol. 2001 Dec; 75(23):11651-63.
    View in: PubMed
  22. Moss B, Ward BM. High-speed mass transit for poxviruses on microtubules. Nat Cell Biol. 2001 Nov; 3(11):E245-6.
    View in: PubMed
  23. Ward BM, Moss B. Visualization of intracellular movement of vaccinia virus virions containing a green fluorescent protein-B5R membrane protein chimera. J Virol. 2001 May; 75(10):4802-13.
    View in: PubMed
  24. Ward BM, Moss B. Golgi network targeting and plasma membrane internalization signals in vaccinia virus B5R envelope protein. J Virol. 2000 Apr; 74(8):3771-80.
    View in: PubMed
  25. Qin S, Ward BM, Lazarowitz SG. The bipartite geminivirus coat protein aids BR1 function in viral movement by affecting the accumulation of viral single-stranded DNA. J Virol. 1998 Nov; 72(11):9247-56.
    View in: PubMed
  26. Ward BM, Medville R, Lazarowitz SG, Turgeon R. The geminivirus BL1 movement protein is associated with endoplasmic reticulum-derived tubules in developing phloem cells. J Virol. 1997 May; 71(5):3726-33.
    View in: PubMed
  27. Pascal E, Sanderfoot AA, Ward BM, Medville R, Turgeon R, Lazarowitz SG. The geminivirus BR1 movement protein binds single-stranded DNA and localizes to the cell nucleus. Plant Cell. 1994 Jul; 6(7):995-1006.
    View in: PubMed

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