Arch Virol (2000) 145: 2411–2420
Murine gammaherpesvirus M11 gene product inhibits apoptosis
and is expressed during virus persistence
D. J. Roy, B. C. Ebrahimi, B. M. Dutia, A. A. Nash, and J. P. Stewart
Department of Veterinary Pathology, University of Edinburgh, Edinburgh, Scotland, U.K.
Accepted May 31, 2000
Summary. The murine gammaherpesvirus (MHV-68) M11 gene encodes a pro-
tein with BH1 domain homology to Bcl-2. We found that the M11 gene product
(MHVBcl-2) protected murine epithelial cells from TNF-␣ induced apoptosis.
M11 was transcribed during early lytic infection in vitro. During early infection
of mice, M11 message was detected in spleen and lung along with lytic cycle
messages. During persistence, lytic cycle gene expression was undetectable but
M11 RNA was still present. This suggests that MHVBcl-2 promotes virus sur-
vival by protecting not only productively infected but also persistently infected
cells from apoptotic death.
Murine gammaherpesvirus (MHV-68) infection of mice offers a small animal
model relevant to aspects of Epstein-Barr virus (EBV) and Kaposi’s sarcoma-
associated virus (KSHV) infection (for review see ). Following intranasal
inoculation, MHV-68 replicates transiently in lungs followed by spread to B cells
and macrophages in the spleen . A splenomegaly then ensues in concert with
a peak in latently infected splenocytes approximately 14 d post infection (p.i.).
Splenomegaly resolves around 21 d p.i. and the spleen then become a reservoir of
latently infected B cells and macrophages [22, 25, 32]. The virus also establishes
long-term persistence in other tissue sites, primarily alveolar epithelial cells in
the lung .
Apoptosis or programmed cell death is a controlled process of cell suicide
that is essential for embryonic development and homeostasis in adult tissues.
However, this process is also important in eliminating cells whose survival might
prove harmful to the organism, thereby providing a defence mechanism against
virus infection. Many viruses encode proteins that inhibit apoptosis of infected