Gamma interferon-dependent clearance of cytomegalovirus infection in salivary glands

Cytomegalovirus (CMV), similar to other members of the
Herpesviridae family, can establish both persistent and latent
infections. Each of the CMVs that are found in many animal species
replicates in the salivary gland, and oral secretion represents a
source of horizontal transmission. Locally restricted replication
characterizes the immunocompetent individual, whereas in the
immunocompromised host, protean disease manifestations occur due to
virus dissemination. The virus is cleared by immune surveillance,
and CD8+ T lymphocytes play a major role. Remarkably, certain cell
types of salivary gland tissues are exempt from CD8+ T-lymphocyte
control of murine CMV infection and require the activity of CD4+ T
lymphocytes. The results presented here suggest that this activity
is a function of Th1 cells. Neutralization of endogenous gamma
interferon abrogated the antiviral activity of Th1 cells but not
that of CD8+ T lymphocytes in other tissues. Neutralization of
endogenous gamma interferon did not interfere with the induction of
the cellular and humoral immune response but acted during the
effector phase. Recombinant gamma interferon could not replace the
function of Th1 cells in vivo and had limited direct antiviral
activity in vitro. The results therefore suggest that gamma
interferon represents one, but not the only, essential factor
involved in salivary gland clearance, establishment of CMV latency,
and, eventually, the control of horizontal transmission.