William
J. Britt, M.D.
Professor of Pediatrics
Phone: 205-996-7762
E-mail:
wbritt@uab.edu
Dr. Britt received his B.A. in chemistry and M.D. from the
University of Arizona. He then completed internship at
McGill University and residency at the University of Minnesota
in pediatrics. After four years as a medical officer in the
Laboratory of Persistent Viral Diseases, NIAID, NIH in Hamilton,
MT, he joined the UAB faculty in 1994. He has a secondary
appointment in the Departments of Microbiology and Neurobiology
and is the Charles A. Alford Professor of Pediatric
Infectious Diseases.
Dr. Britt’s laboratory focuses on two important aspects of the
biology of herpesviruses: virus assembly and the pathogenesis of
human cytomegalovirus (CMV) infections. Regarding virus
assembly, he and his colleagues have developed in vitro
assay systems that permit the identification and
characterization of critical protein interactions related to
virus assembly. Using BAC-derived infectious clones, he
has utilized virus genetics to understand the role of different
viral proteins in the assembly of an infectious particle.
His results show that interactions between viral tegument and
envelope proteins are essential for infectious particle assembly
and that inhibition of these interactions can limit envelopment
and, therefore, virus assembly. Regarding herpesvirus
pathogenesis, his laboratory has played a key role in
elucidating the role of cytokines in the pathogenesis of
CMV-induced mucosal disease in the human gastrointestinal tract.
His laboratory also has investigated a small animal model of
central nervous system (CNS) disease associated with CMV
infections.
He has exploited a finding that newborn mice infected with
murine CMV develop CNS infection that leads to maldevelopment of
the CNS, including abnormalities in cellular migration. This
system is now being characterized both in terms of host
responses and viral genes that are required for this disease
phenotype.
Selected Publications
-
Britt, W.J., Jarvis, M.A.,
Seo,
J.Y., Drummond, D.D. and JA Nelson. Rapid genetic
engineering of human cytomegalovirus using a lambda phage based linear
recombination system: Demonstration that pp28 (UL99) is essential for
production of infectious virus.
J.Virol. 78:539-543, 2004.
-
Jarvis, M.A., Jones, T.R., Drummond, D.D., Smith,
P.P., Britt, W.J., Nelson, J.A. and Baldick,
C.J. Phosphorylation of human cytomegalovirus glycoprotein B (gB)
at the acidic cluster (AC) casein kinase 2 site (Ser900)
is required for localization of gB
to the trans-Golgi network
and efficient virus replication. J.Virol. 78:285-293, 2004.
-
Wang, Z.,
LaRosa, C.,
Maas, R., Ly H.,, Brewer, J.,
Mekhoubad, S., Daftarian, P.,
Longmate, J.,
Britt, W.J. and Diamond, D.J. Recombinant modified
vaccinia virus Ankara expressing a
soluble form of glycoprotein B causes durable immunity and
neutralizing antibodies against multiple strains of human
cytomegalovirus. J.Virol.
78:3965-3976, 2004.
-
Netterwald, J.R.,
Jones, T.R., Britt, W.J., Yang, S.J., McCrone, I.P. and Zhu, H.
Postattachment events associated
with viral entry are necessary for induction of
interferon-stimulated genes by human cytomegalovirus. J.Virol. 78:6688-6691,
2004.
-
Britt, W.J. and
Boppana,
S. Human cytomegalovirus virion
proteins. Hum.
Immunol.
65:395-402, 2004.
-
Varnum, S.M., Streblow, D.N., Monroe, M.E., Smith,
P., Auberry, K.J., Pasa-Tolic, L.,
Wang, D., Camp II, D.G., Rodland,
K., Wiley, S., Britt, W., Shenk, T.,
Smith, R.D. and Nelson, J.A. Identification of proteins in
human cytomegalovirus (HCMV) particles: the HCMV proteome. J. Virol. 78:10960-10966,
2004.
-
Gredmark, S., Britt,
W.J., Xie, X., Lindom, L. and
Söderberg-Nauclér,
C. Human cytomegalovirus induces inhibition of macrophage
differentiation by binding to human aminopeptidase
N/CD13. J.Immunol.
173:4897-907, 2004.
-
Yu, X., Shah, S.,
Atanasov,
I., Lo, P., Liu, F., Britt, W.J. and ZH Zhou, Z.H.
Three-dimensional localization of the
smallest capsid protein in the human cytomegalovirus capsid. J.Virol. 79:1327-1332,
2005.
-
Britt, W.J., Jarvis, M., Drummond, D. and Mach,
M. Antigenic domain 1 (AD-1) is required for
oligomerization
of human cytomegalovirus glycoprotein B. J.
Virol. 79:4066-4079, 2005.
-
Mach, M.,
Kropff, B.,
Kryzyzaniak, M. and Britt, W.
Complex formation of glycoproteins M and N of human
cytomegalovirus: structural and functional aspects. J.Virol. 79:2160-2170,
2005.