Arch Virol (2005) 150: 797–803
Cell-mediated cytotoxicity of murine
cytomegalovirus-infected target cells allows
for release of residual infectious virus
R. D. Dix
and S. W. Cousins
Department of Ophthalmology, Harvey & Bernice Jones Eye Institute,
University of Arkansas for Medical Sciences, Little Rock, Arkansas, U.S.A.
Department of Microbiology and Immunology, University of Arkansas
for Medical Sciences, Little Rock, Arkansas, U.S.A.
Department of Ophthalmology, Bascom Palmer Eye Institute,
University of Miami School of Medicine, Miami, Florida, U.S.A.
Received October 4, 2004; accepted November 1, 2004
Published online December 21, 2004
Summary. Although cell-mediated cytotoxicity effectively kills target virus-
infected cells, no careful consideration has been given to the fate of infectious
progeny virus contained within target cells following the cytolytic event. To
address this issue with respect to murine cytomegalovirus (MCMV) pathogen-
esis, we developed a rapid semiquantitative assay for infectious MCMV based
on expression of β-galactosidase using a LacZ-expressing recombinant MCMV.
Simultaneous use of this assay in combination with a modiﬁed cell-mediated cyto-
toxicity assay revealed that cytotoxicity of MCMV-infected target cells mediated
by MCMV-immune splenic cells does not lead to inactivation of intracellular
Virus infection stimulates an immune response within the host that often leads to
the clearance of virus-infected cells through a variety of mechanisms that include
cytotoxic effector cells such as natural killer (NK) cells and cytotoxic CD8+
T cells. Two distinct pathways of lymphocyte-mediated cytotoxicity have been
recognized that fall under the broad categories of perforin-mediated cytotoxicity
and receptor-mediated cytotoxicity[5, 7, 9]. These pathways use distinct mediators
of cytolysis, but both involve induction of a series of intracellular events that
ultimately lead to the death of the virus-infected target cell via lysis and/or