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Brian M. Ward, Ph.D.

Contact Information

Phone Numbers

Office: (585) 275-9715

Fax: (585) 473-9573

Research Labs

Molecular Mechanisms of Poxvirus Morphogenesis and Egress

Lab: (585) 275-5334

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Biography

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.

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, 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.

Credentials

Faculty Appointments

Education

1992
BS | Indiana University
Microbiology

1994
MS | Univ of Illinois-Urbana
Microbiology

1998
PhD | Univ of Illinois-Urbana
Microbiology

Awards

2005
Who's Who in Medical Science Educatio
Sponsor: AcademicKeys

2003
Fellows Award For Research Excellence
Sponsor: NIH
Location: Bethesda, MD

2002
Finalist - Norman P. Salzman Memorial Award In Virology
Sponsor: NIH
Location: Bethesda MD

2002
Fellows Award For Research Excellence
Sponsor: NIH
Location: Bethesda MD

2001
Finalist - Norman P. Salzman Memorial Award In Virology
Sponsor: NIH
Location: Bethesda MD

2001
Fellows Award For Research Excellence
Sponsor: NIH
Location: Bethesda MD

1998 - 2003
Intramural Research Training Assistant Postdoctoral Fellowship
Sponsor: NIH
Location: Bethesda MD

1994
Francis M. and Harlie M. Clark Research Grant
Sponsor: University of Illinois
Location: Urbana- Champaign, IL

1991 - 1992
Howard Hughes Undergraduate Research Fellowship
Sponsor: Indiana University
Location: Bloomington, IN

1991 - 1992
High Scholastic Achievement
Sponsor: Indiana University
Location: Bloomington, IN

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Publications

Journal Articles

2/2014
Baker JL, Ward BM. "Development and comparison of a quantitative TaqMan-MGB real-time PCR assay to three other methods of quantifying vaccinia virions." Journal of virological methods.. 2014 Feb 0; 196:126-32. Epub 2013 Nov 08.

2013
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 pathogens.. 2013 9(6):e1003481. Epub 2013 Jun 27.

8/2012
Chan WM, Ward BM. "The A33-dependent incorporation of B5 into extracellular enveloped vaccinia virions is mediated through an interaction between their lumenal domains." Journal of virology.. 2012 Aug 0; 86(15):8210-20. Epub 2012 May 23.

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