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The
Molecular Basis of Viral Pathogenesis 
Our lab studies the replication and pathogenesis of several viruses that
produce disease in humans:
1. Kaposi's sarcoma-associated herpesvirus (KSHV). KSHV is a large DNA
virus whose genome was initially discovered in Kaposi's sarcoma (KS),
an endothelial tumor common in AIDS patients. A member of the lymphotropic
family of herpesviruses, KSHV's principal reservoir is the B cell. Our
group has developed systems to grow this virus in cultured B cells and
endothelia; using these systems we generated blood tests for viral infection
and explored the distribution of infection in the population. These epidemiologic
studies strongly implicated KSHV in the causation of KS. Current work
centers on identifying the viral genes expressed in KS tumors and in other
latently infected cells, and on understanding how these genes link infection
to tumorigenesis. We are also identifying and characterizing viral genes
linked to the stimulation of angiogenesis and the evasion of host immunity,
and are studying the molecular mechanisms that promote viral reactivation
from latency.
2. Hepatitis delta virus (HDV). HDV is an RNA virus that produces severe
acute and chronic liver injury. It employs an RNA-dependent RNA replication
reaction, but unlike all other RNA viruses does not encode its own polymerase.
Current work seeks to identify and characterize the responsible host replication
machinery, believed by many to involve RNA polymerase II.
Selected Publications:
Lagunoff,M, Majeti,R, A Weiss and D Ganem (1999) Deregulated signal transduction
by the K1 gene product of the Kaposi's sarcoma-associated herpesvirus.
Proc Nat Acad Sci USA 96: 5704-5709.
Lukac,D, J Kirshner and D Ganem (1999) Transcriptional activation by the
ORF 50 protein of KSHV/HHV-8 is required for lytic viral reactivation
in B cells. J. Virol. 73: 9348-9361.
Bell, P, R Brazas, D Ganem and G Maul (2000) Hepatitis delta replication
generates complexes of L-HDAg and antigenomic RNA that affiliate with
and alter ND10 domains. J. Virol, 74:5329-5336.
Coscoy, L and D Ganem (2000) Kaposi's sarcoma-associated herpesvirus encodes
two novel proteins that downregulate cell surface MHC class I chains by
enhancing their endocytosis. Proc Nat Acad Sci USA Proc Nat Acad Sci USA
97: 8051-8056: 2000
Coscoy, L and D Ganem (2001) A viral protein that selectively downregulates
ICAM-1 and B7-2, key components of immunological synapse formation and
T cell costimulation, submitted.
Lukac, D.M., Garibyan, L., Kirshner, J. and Ganem, D. (2001) DNA binding
by the Kaposi's sarcoma-associated herpesvirus lytic switch protein is
necessary for transcriptional activation of two viral delayed early promoters.
J. Virol. 75: 6786-6799.
Coscoy, L, Sanchez, D. and Ganem, D. (2001) A novel class of herpesvirus-encoded,
membrane-bound E3 ubiquitin ligases regulates endocytosis of proteins
involved in immune recognition. J. Cell Biol. 155:1265-1273.
Liu, Y-T., Brazas, R. and Ganem, D. (2001) Efficient hepatitis delta virus
RNA replication in avian cells requires permissive factor(s) from mammalian
cells. J. Virol. 75: 7489-7493.
Lagunoff, M, Roy, A-M., Venetsanakos, E., Abbey, N., Herndier, B., Bechtel,
J., McMahon, M. and Ganem, D. (2002) De novo infection and serial transmission
of Kaposi's sarcoma-associated herpesvirus (KSHV) in cultured endothelial
cells. J. Virol. 76:2440-2448.
Sanchez, D, Coscoy, L. and Ganem, D. (2002) Functional organization of
MIR2, a novel viral regulator of selective endocytosis. J Biol Chem. 277:6124-6130.
Baron, J.L., Gardiner, L., Nishimura, S., Locksley, R. and Ganem, D. (2002)
A novel NKT cell subset mediates liver injury in a transgenic mouse model
of hepatitis B virus infection. Immunity, in press.
Contact Information:
Email: ganem@cgl.ucsf.edu
Phone: 415/ 476-2826
Address: Box 0414, Room HSE 420
The University of California, San Francisco, CA 94143, (415) 476-9000
Copyright 2003, The Regents of the University of California.
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