Arch Virol (2001) 146: 2219–2225
Inhibition of apoptosis by primary isolates
of herpes simplex virus
K. R. Jerome, R. Fox, Z. Chen, P. Sarkar
, and L. Corey
Department of Laboratory Medicine, University of Washington, Seattle,
Washington, and Program in Infectious Diseases, Fred Hutchinson
Cancer Research Center, Seattle, Washington, U.S.A.
Accepted June 19, 2001
Summary. HSV-1 inhibits apoptosis of the infected cell, presumably to increase
viral yield. Weaker anti-apoptotic activity was previously reported in laboratory-
adapted HSV-2, but not in two low-passage clinical HSV-2 isolates, suggesting
that the anti-apoptotic effect might result from adaptation to laboratory growth.
We therefore assembled a large panel of clinical strains of HSV-1 and HSV-2.
Clinical and laboratory strains of HSV-1 strongly inhibited apoptosis of Jurkat
cells, as determined by morphologic change or caspase activation, while clin-
ical HSV-2 strains showed no inhibitory activity in Jurkat cells. These ﬁndings
suggest fundamentaldifferences between HSV-1 and HSV-2in their manipulation
of host cell apoptosis.
Viruseshave evolved mechanisms to evade the defense responses of their hosts.As
one defense, many infected cells respond to viral infection by undergoing apop-
tosis ; failing this, infected cells can be induced into apoptosis by members of
the immune system such as cytotoxic T lymphocytes (CTL) . Apoptosis pre-
sents a major threat to viruses, since apoptotic cells are poor hosts for viral replica-
tion . Thus, many viruses have evolved intricate anti-apoptotic mechanisms.
Herpes simplex virus (HSV) protects infected cells from apoptosis through
the action of several genes and gene products, including Us3 , Us5 (gJ) ,
ICP22 , ICP27 , and LAT . Together, these proteins protect infected
Current address: P. Sarkar, Mount Sinai School of Medicine, New York, NY 10027,