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Brian
Ward
Assistant
Professor of Microbiology & Immunology
Primary Appointment: Graduate
Degree Programs |
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| Contact Information: | ||
| University
of Rochester School of Medicine and Dentistry 601 Elmwood Ave, Box 672 Rochester, New York 14642 |
Medical
Center Room 3-9816 (Lab)/ 3-9619 (Office) Phone: (585) 275-9715 Fax: (585) 473-9573 E-Mail: Brian_Ward@URMC.Rochester.edu |
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- 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.
- A more detailed description of this laboratory and its research is also available.
- Recent Publications
- Earley AK, Chan WM, Ward BM "The Vaccinia Virus B5 Protein Requires A34 for Efficient Intracellular Trafficking from the ER to the Site of Wrapping and Incorporation into Progeny Virions." J Virol. 2007 Dec 19;
- Ward, B. M. "Visualization and characterization of the
intracellular movement of vaccinia virus intracellular mature virions."
J Virol 79(8): 4755-63, 2005.
- Ward BM. Pox, Dyes, and Videotape: Making Movies of
Fluorescently Labeled Vaccinia Virions. In S.N. Isaacs (ed.), Poxvirus
Protocols.
Methods Mol Biol. 2004;269:205-18.
Supplemental Material - 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;78 2486-2493
- 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. 78 2348-2356, 2004
- 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. 78 2357-2366, 2004
- 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.
77:4113-26, 2003.
Supplemental Material (Movies) - Moss B, Ward BM. High-speed mass transit for poxviruses on
microtubules. Nat
Cell Biol. 3:E245-6, 2001.
Supplemental Material (Movies) - Ward BM, Moss B. Vaccinia virus intracellular movement is associated with microtubules and independent of actin tails. J Virol. 75:11651-63, 2001.
- Ward BM, Moss B. Visualization of intracellular movement
of vaccinia virus virions containing a green fluorescent protein-B5R
membrane protein chimera. J Virol.
75:4802-13, 2001.
Supplemental Material (Movies) - Ward BM, Moss B. Golgi network targeting and plasma membrane internalization signals in vaccinia virus B5R envelope protein. J Virol. 74:3771-80, 2000.
- Review Publications
- Ward BM. "The longest micron; transporting poxviruses out of the cell." Cell Microbiol. 2005 Nov;7(11):1531-8. Review.
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