Joseph Regenstein Distinguished
Department of Molecular Genetics and
Department of Biochemistry and
The Cancer Research Center
Committee on Genetics
Committee on Microbiology
Sc.D., Johns Hopkins, 1956
Phone: (773) 702-1898
The University of Chicago
910 East 58th Street
Chicago, Illinois 60637
Related Research Interests:
Bernard Roizman, Sc.D.
Herpes Simplex Virus Genome Structure, Gene Expression,
Herpes simplex viruses are large DNA pathogens encoding
at least 84 proteins. Our research focuses on the molecular biology of
these viruses and in particular on two areas: The first concerns the
mechanisms by which the virus subjugates the infected cell, evades host
responses, and makes the cell produce many thousands of virus
particles. Current studies center on the functions of several proteins
(i) a multifunctional protein designated ICP0 that block the silencing
of the viral DNA on entry into cells and acts as a ubiquitin ligase
that targets cellular proteins potentially inimical to the virus (ii) a
protein designated UL41 that selectively degrades mRNA to block host
responses to infection, (iii) a viral protein kinase known as US3 that
blocks programmed cell death induced by viral gene products, cellular
factors or exogenous agents, and (iv), a viral protein known as ICP22
that scavenges the infected cell for a cellular protein that it uses to
enhance viral protein synthesis. The second area of research is based
on the accumulated knowledge regarding viral gene functions and the
ability to genetically engineer novel viruses. Our objective is to make
novel viruses that specifically target cancer cells and selectively
destroy them without affecting normal cells. These studies have
generated highly promising results and may lead to the transformation
of a human pathogen into a therapeutic agent.
Taddeo, B., Zhang, W., Lakeman, F., and Roizman, B.
(2004). Cells lacking NF-kB or in which NF-kB is not activated vary
with respect to ability to sustain herpes simplex virus 1 replication
and are not susceptible to apoptosis induced by a replication
incompetent virus. J. Virol. 78:11615-11621.
Escaltine, A., Taddeo, B. and Roizman, B. (2004). The UL41
protein of herpes simplex virus mediates selective degradation of
cellular mRNAs. Proc. Nat. Acad. Sci. (USA ) 101:18165-18170.
Zhou, G. and Roizman, B. (2005). Characterization
of a recombinant herpes simplex virus 1 targeted to enter cells via the
IL13Ra2 receptor of malignant glioma cells. J. Virol.79:5272-5277.
Durand, L.O, Advani, S.J. and Roizman, B. (2005). The
carboxyl-terminal domain of RNA POL II is phosphorylated by a complex
containing cdk9 and the infected-cell protein No. 22 of herpes simplex
virus 1. J. Virol, 79:6757-6762.
Poon, A.P.W. and Roizman, B. (2005). The herpes simplex
virus 1 ICP22 regulates the accumulation of a shorter mRNA and of a
truncated US3 protein kinase that exhibits altered
functions. J. Virol. 79:8470-8479.
Liang, Y., Kurakin, A., and Roizman, B. (2005). Herpes
simplex virus 1 ICP0 forms a complex with CIN85 and Cbl and mediates
the degradation of EGFR from cell surfaces. Proc. Nat. Acad. Sci (USA)
Gu., H., Liang, Y., Mandel, G. and Roizman, B. (2005).
Components of the REST/CoREST/HDAC repressor are disrupted, modified
and translocated in herpes simplex virus 1 infected cells. Proc. Nat.
Acad. Sci. (USA) 102:5771-7576.
Roizman, B., Gu, H, and Mandel, G. (2005). The frst 30
minutes in the life of a virus: unREST in the nucles. Cell
Mezhir, J.J., Advani, S.J., Smith, K.D., Darga, T.E.,
Poon, A.P.W., Schmidt, H., Posner, M.C., Roizman, B., an Weichselbaum,
R.R. (2005). Ionizing radiation activates late herpes simplex
virus 1 promoters via the p38 pathway in tumors treated with oncolytic
viruses. Cancer Research 65:9479-9484.
Hellums, E.K., Market, J.M., Parker, J.N., He, B.,
Perbal, B., Roizman, B., Whitley, R.J., Langford, C.P., Bharara, S.,
and Gillespie, G.Y. (2005). Increased efficacy of an
interleukin-12-secreting herpes simplex virus in a syngeneic
intracranial murine glioma model. Neuro-Oncology 7?213-224.
Kamiyama, H., Zhou, G., and Roizman, B. (2006). Herpes
simplex virus 1 recombinant virions exhibiting the amino terminal
fragment of urokinase-type plasminogen activator can enter cells via
the cognate receptor. Gene Ther. 13:621-629.
Smith, K.D., Mezhir, J.J., Bickenbach, K., Veerapong,
J., Charron, J., Posner, M.C., Roizman, B., and Weichselbaum, R.R.
(2006). Activated MEK suppresses activation of PKR and enables
efficientreplication and in vivo oncolysis by 134.5-
mutants of herpes simplex virus 1. J. Virol. 80:1110-1120.
Taddeo, B., Zhang, W., and Roizman, B. (2006). The UL41
protein of herpes simplex virus 1 degrades RNA by endonucleolytic
cleavage in absence of other cellular or viral proteins. Proc Nat Acad
Sci (USA) 103:2827-2832.
Benetti, L. and Roizman, B. (2006). Protein kinase B/Akt
is present in activated form throughout the entire replicative cycle of
US3 mutant virus but only at early times after infection
with wild-type herpes simplex virus 1. J. Virol. 80:3341-3348.
Liang, Y and Roizman, B. (2006). The state and role of
Src family kinases in the replication of herpes simplex virus 1. J.
Poon, A.P.W., Benetti, L., and Roizman, B. (2006). US3
and US3.5 protein kinases of herpes simplex virus 1 differ
with respect to their functions in blocking apoptosis and in virion
maturation and egress. J. Virol. 80:3752-3764.
Zhou, G., and Roizman, B. (2006). Construction and
properties of a herpes simplex virus 1 designed to enter cells solely
via the ILI32 receptor. Proc Nat Acad Sci 103:5508-5513.
Campadelli-Fiume, G., and Roizman, B. (2006). The egress
of herpesviruses from cells: the unanswered questions. Letter to the
Editor. J Virol 80:6716-6719.
Liang, L., and Roizman, B. (2006). Herpes simplex virus
1 precludes replenishment of the short-lived receptor of tumor necrosis
factor alpha by virion host shutoff-dependent degradation of its mRNA.
J Virol 80:7756-7759.
Poon, A.P.W., Gu, H., and Roizman, B. (2006). ICPO and
US3 protein kinase of herpes simplex virus 1 independently block
histone and deacetylation to enable gene expression. Proc Nat Acad Sci
Taddeo, B., and Roizman, B. (2006). The virion host
shutoff (UL41) protein of herpes simplex virus 1 is an
endoribonuclease with a substrate specificity similar to that of RNase
A. J Virol 80:9341-9345.
Roizman, B., and Taddeo, B. (2006). HSV-1 and the Host
Cell: a story of global conspiracies, plots and counterplots. Alpha Herpesviruses; Molecular and
Cellular Biology. R. Sandhi-Golidin Ed. Horizon Scientific
Advani, S., Mezhir, J.J., Roizman, B., and Weichselbaum,
R.R. (2006). ReVOLT: Radiation
Enhanced Viral Oncolytic Therapy. Int J Radiation Oncology
Biol Phys 66:637-646.
Roizman, B. and Campadelli-Fiume, G. (2006). Herpes
simplex virus. Fundamentals of
Molecular Virology. N.H. Acheson Ed. Wiley, pp134-146.
Baines, J.D., Wills, E., Jacob, R.J., Pennington, J. and
Roizman B. (2007). Glycoprotein M of herpes simplex virus 1 is
incorporated into virions during budding at the inner nuclear membrane.
J Virol 81:800-812.
Pellet, P.E. and Roizman, B. (2007). The Family
Herpesviridae: A brief introduction. Fields'
Virology 5th Edition. D.M. Knipe, P. Howley, D.E. Griffin, R.A.
Lamb, M.A. Martin, B. Roizman, and S.E. Straus, Editors.
Lippincott-Williams and Wilkins, New York, N.Y., pp2479-2499.
Roizman B., Knipe, D.M. and Whitley, R.J. (2007). The
replication of Herpes simplex viruses. Fields' Virology 5th Edition. D.M.
Knipe, P. Howley, D.E. Griffin, R.A. Lamb, M.A. Martin, B. Roizman and
S.E. Straus, Editors. Lippincott-Williams and Wilkins, New York, N.Y.
Poon, A.P.W. and Roizman, B. (2007). Separation of
receptor binding and pro-fusogenic domains of glycoprotein D of herpes
simplex virus 1 into distinct interacting proteins. Proc Nat Acad Sci
Kalamvoki, M. and Roizman, B. (2007). Bcl-2 blocks
accretion or depletion of stored calcium, but has no effect on the
redistribution of the IP3-1 receptor mediated by glycoprotein E of
herpes simplex virus 1. J Virol 81:6316-6325.
Kari, I., Syrjänen, S., Johansson, B., Peri, P.,
He, B., Roizman, B. and Hukkanen, V. (2007). Antisense RNA Directed to
the Human Papillomavirus Type 16 E7 mRNA from Herpes Simplex Virus Type
1 Derived Vectors is Expressed in CaSki Cells and Downregulates E7
mRNA. J Virol 4:47-58.
Roizman, B. and Campadelli-Fiume, G. (2007). Viral genes
and their function. Human
Herpesviruses: Biology, Therapy and Immunoprophylaxis. Arvin,
A.M., Campadelli-Fiume, G., Mocarski, E., Moore, P.S., Roizman, B.,
Whitley, R.J. and Yamanishi, K, Editors. Cambridge Univ Press, pp70-92.
Roizman, B. and Taddeo, B. (2007). The strategy of viral
replication and takeover of the host cell. Human Herpesviruses: Biology, Therapy and
Immunoprophylaxis. Arvin, A.M., Campadelli-Fiume, G., Mocarski,
E., Moore, P.S., Roizman, B., Whitley, R.J. and Yamanishi, K., Editors.
Cambridge Univ Press, pp163-173.
Taddeo, B., Sciortino, M.T., Zhang, W. and Roizman, B.
(2007). Interaction of herpes simplex virus RNase with VP16 and VP22 is
required for the accumulation of the protein but not for accumulation
of mRNA. Proc Nat Acad Sci USA 104:12163-12168.
Skelly, C.L., Amito Chandiwal, A., Vocisky, J.F., Ralph,
R., Weichselbaum, R.R. and Roizman, B. (2007). Attenuated herpes
simplex virus 1 blocks arterial apoptosis and intimal hyperplasia
induced by balloon angioplasty and reduced blood flow. Proc Nat Acad
Benetti, L. and Roizman, B. (2007). In transduced cells,
the US3 protein kinase of herpes simplex 1 precludes activation and
induction of apoptosis by transfected procaspase 3. J Virol
Veerapong, J., Bickenbach, K.A., Shao, M., Smith, K.D.,
Posner, M.C., Roizman, B. and Weichselbaum, R.R. (2007). Systemic
delivery of 134.5-deleted herpes simplex virus 1
selectively targets and treat distant human xenograft tumors that
express high MEK activity. Cancer Res 67:8301-8306.
Sciortino, M.T., Taddeo, B., Giuffrè-Cuculletto,
M., Medici, M.A., Mastino, A. and Roizman, B. (2007). Replication
competent herpes simplex virus 1 isolates selected from cells
transfected with a BAC-DNA lacking solely the UL49 gene vary
with respect to the defect in the UL41 gene encoding the
host shutoff RNase. J Virol 81:10924-10932.
Khodarev, N.N., Minn, A.J., Efimova, E.V., Darga, T.E.,
Labay, E., Beckett, M., Mauceri, H., Roizman, B. and Weichselbaum, R.R.
(2007). Signal transducer and activator of transcription 1 regulates
both cytotoxic and prosurvival functions in tumor cells. Cancer
Gu, H. and Roizman, B. (2007). Herpes simplex virus ICP0
blocks the silencing of viral DNA by dissociating HDACs from the
CoREST/REST complex. Proc Nat Acad Sci (USA) 104:17174-17139.
Yang, K., Poon, A.P.W., Roizman, B. and Baines, J.D.
(2008). Temperature-sensitive mutations in the putative herpes simplex
virus 1 terminase subunits UL15 and UL33 preclude
viral DNA cleavage/packaging and interaction with pUL28 at
the nonpermissive temperature. J Virol 82:487-494.
Kalamvoki, M., Qu, J. and Roizman, B. (2008).
Translocation and colocalization of ICP4 and ICP0 in cells infected
with herpes simplex virus 1 mutants lacking glycoprotein E,
glycoprotein I or the virion host shutoff product of UL41
gene. J Virol 82:1701-1713.
Jovasevic, V., Liang, L. and Roizman, B. (2008).
Proteolytic cleavage of VO1-2 is required for the release of herpes
simplex virus 1 DNA into the nucleus. J Virol 82:2211-2219.
Smith-Donald, B.A., Durand, L.O. and Roizman, B. (2008).
The role of cellular phosphatase cdc25C in herpes simplex virus 1
replication. J Virol 82:4527-4532.
Smith-Donald, B.A., and Roizman, B. (2008). The
interaction of herpes simplex virus 1 regulator protein ICP22 with the
cdc25C phosphatase is enabled in vitro by viral protein kinases US3
and UL13. J Virol 82:4533-4543.
Liang, L. and Roizman, B. (2008). The expression of
interferon y dependent genes is blocked independently by the virion
host shutoff RNase and by the US3 protein kinase. J Virol
Faculty and Research