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Brian M. Ward, Ph.D.

Brian M. Ward, Ph.D.

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About Me

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...
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.

Faculty Appointments

Professor - Department of Microbiology and Immunology (SMD)

Credentials

Post-doctoral Training & Residency

Postdoctoral Fellow, National Institutes of Health, Bethesda, MD.
Advisor: Bernard Moss 1998 - 2003

Education

PhD | Univ of Illinois-Urbana. Microbiology. 1998

MS | Univ of Illinois-Urbana. Microbiology. 1994

BS | Indiana University. Microbiology. 1992

Awards

Who's Who in Medical Science Education. 2005

Fellows Award For Research Excellence. 2003

Finalist - Norman P. Salzman Memorial Award In Virology. 2002

Fellows Award For Research Excellence. 2002

Finalist - Norman P. Salzman Memorial Award In Virology. 2001

Fellows Award For Research Excellence. 2001

Intramural Research Training Assistant Postdoctoral Fellowship. 1998 - 2003

Francis M. and Harlie M. Clark Research Grant. 1994

Howard Hughes Undergraduate Research Fellowship. 1991 - 1992

High Scholastic Achievement. 1991 - 1992

Research

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...
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.

Publications

Journal Articles

The Molluscum Contagiosum Gene MC021L Partially Compensates for the Loss of Its Vaccinia Virus Homolog, F13L.

Monticelli SR, Bryk P, Ward BM

Journal of virology.. 2020 September 2994 (20)Epub 09/29/2020.

Vaccinia Virus Phospholipase Protein F13 Promotes Rapid Entry of Extracellular Virions into Cells.

Bryk P, Brewer MG, Ward BM

Journal of virology.. 2018 June 192 (11)Epub 05/14/2018.

Development and comparison of a quantitative TaqMan-MGB real-time PCR assay to three other methods of quantifying vaccinia virions.

Baker JL, Ward BM

Journal of virological methods.. 2014 February 196 :126-32. Epub 11/08/2013.

Host factor SAMHD1 restricts DNA viruses in non-dividing myeloid cells.

Hollenbaugh JA, Gee P, Baker J, Daly MB, Amie SM, Tate J, Kasai N, Kanemura Y, Kim DH, Ward BM, Koyanagi Y, Kim B

PLoS pathogens.. 2013 9 (6):e1003481. Epub 06/27/2013.

The A33-dependent incorporation of B5 into extracellular enveloped vaccinia virions is mediated through an interaction between their lumenal domains.

Chan WM, Ward BM

Journal of virology.. 2012 August 86 (15):8210-20. Epub 05/23/2012.

Increased interaction between vaccinia virus proteins A33 and B5 is detrimental to infectious extracellular enveloped virion production.

Chan WM, Ward BM

Journal of virology.. 2012 August 86 (15):8232-44. Epub 05/23/2012.

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.

Chen G, Ward BM, Yu EK, Chinchar VG, Robert J

Journal of virology.. 2011 November 85 (21):11131-8. Epub 08/24/2011.

The taking of the cytoskeleton one two three: how viruses utilize the cytoskeleton during egress.

Ward BM

Virology.. 2011 March 15411 (2):244-50. Epub 01/15/2011.

The inability of vaccinia virus A33R protein to form intermolecular disulfide-bonded homodimers does not affect the production of infectious extracellular virus.

Chan WM, Kalkanoglu AE, Ward BM

Virology.. 2010 December 5408 (1):109-18. Epub 10/13/2010.

There is an A33-dependent mechanism for the incorporation of B5-GFP into vaccinia virus extracellular enveloped virions.

Chan WM, Ward BM

Virology.. 2010 June 20402 (1):83-93. Epub 04/07/2010.

Simulation and prediction of the adaptive immune response to influenza A virus infection.

Lee HY, Topham DJ, Park SY, Hollenbaugh J, Treanor J, Mosmann TR, Jin X, Ward B, Miao H, Holden-Wiltse J, Perelson AS, Zand M, Wu H

Journal of virology.. 2009 July 83 (14):7151-65. Epub 05/13/2009.

Vaccinia virus protein F12 associates with intracellular enveloped virions through an interaction with A36.

Johnston SC, Ward BM

Journal of virology.. 2009 February 83 (4):1708-17. Epub 12/03/2008.

Using fluorescent proteins to study poxvirus morphogenesis.

Ward BM

Methods in molecular biology.. 2009 515 :1-11. Epub 1900 01 01.

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.

Earley AK, Chan WM, Ward BM

Journal of virology.. 2008 March 82 (5):2161-9. Epub 12/19/2007.

The longest micron; transporting poxviruses out of the cell.

Ward BM

Cellular microbiology.. 2005 November 7 (11):1531-8. Epub 1900 01 01.

Visualization and characterization of the intracellular movement of vaccinia virus intracellular mature virions.

Ward BM

Journal of virology.. 2005 April 79 (8):4755-63. Epub 1900 01 01.

Vaccinia virus A28L gene encodes an essential protein component of the virion membrane with intramolecular disulfide bonds formed by the viral cytoplasmic redox pathway.

Senkevich TG, Ward BM, Moss B

Journal of virology.. 2004 March 78 (5):2348-56. Epub 1900 01 01.

Vaccinia virus entry into cells is dependent on a virion surface protein encoded by the A28L gene.

Senkevich TG, Ward BM, Moss B

Journal of virology.. 2004 March 78 (5):2357-66. Epub 1900 01 01.

Vaccinia virus A36R membrane protein provides a direct link between intracellular enveloped virions and the microtubule motor kinesin.

Ward BM, Moss B

Journal of virology.. 2004 March 78 (5):2486-93. Epub 1900 01 01.

Pox, dyes, and videotape: making movies of GFP-labeled vaccinia virus.

Ward BM

Methods in molecular biology.. 2004 269 :205-18. Epub 1900 01 01.

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.

Katz E, Ward BM, Weisberg AS, Moss B

Journal of virology.. 2003 November 77 (22):12266-75. Epub 1900 01 01.

Mapping and functional analysis of interaction sites within the cytoplasmic domains of the vaccinia virus A33R and A36R envelope proteins.

Ward BM, Weisberg AS, Moss B

Journal of virology.. 2003 April 77 (7):4113-26. Epub 1900 01 01.

Macromolecular trafficking within and between plant cells as revealed by virus movement proteins.

Sondra G. Lazarowitz, Roisin C. McGarry, Janet E. Hill, Yoshimi D. Barron, Daniel Gold, Miguel F. Carvalho, Anton A. Sanderfoot, and Brian M. Ward.

In Biology of Plant-Microbe Interactions vol. 3. (Sally A. Leong, Caitilyn Allen, and Eric W. Triplett, eds.). 2002; .

Vaccinia virus intracellular movement is associated with microtubules and independent of actin tails.

Ward BM, Moss B

Journal of virology.. 2001 December 75 (23):11651-63. Epub 1900 01 01.

High-speed mass transit for poxviruses on microtubules.

Moss B, Ward BM

Nature cell biology.. 2001 November 3 (11):E245-6. Epub 1900 01 01.

Visualization of intracellular movement of vaccinia virus virions containing a green fluorescent protein-B5R membrane protein chimera.

Ward BM, Moss B

Journal of virology.. 2001 May 75 (10):4802-13. Epub 1900 01 01.

Golgi network targeting and plasma membrane internalization signals in vaccinia virus B5R envelope protein.

Ward BM, Moss B

Journal of virology.. 2000 April 74 (8):3771-80. Epub 1900 01 01.

Nuclear export in plants. Use of geminivirus movement proteins for a cell-based export assay.

Brian M. Ward, and Sondra G. Lazarowitz.

Plant Cell. 1999; .

The bipartite geminivirus coat protein aids BR1 function in viral movement by affecting the accumulation of viral single-stranded DNA.

Qin S, Ward BM, Lazarowitz SG

Journal of virology.. 1998 November 72 (11):9247-56. Epub 1900 01 01.

Intercellular and intracellular trafficking: What we can learn from geminivirus movement. In Cellular Integration of Signal Pathways in Plants.

Sondra G. Lazarowitz, Brian M. Ward, Anton A. Sanderfoot, and Christina M. Laukaitis.

NATO Advanced Study Institute Series, Vol. H 104. (F.Lo Schiavo, R.L. Last, G.Morelli, and N.V. Raikhel ed.). 1998; pp. 275-288.

The geminivirus BL1 movement protein is associated with endoplasmic reticulum-derived tubules in developing phloem cells.

Ward BM, Medville R, Lazarowitz SG, Turgeon R

Journal of virology.. 1997 May 71 (5):3726-33. Epub 1900 01 01.

The geminivirus BR1 movement protein binds single-stranded DNA and localizes to the cell nucleus.

Pascal E, Sanderfoot AA, Ward BM, Medville R, Turgeon R, Lazarowitz SG

The Plant cell.. 1994 July 6 (7):995-1006. Epub 1900 01 01.