All humans become infected with multiple
herpesviruses during childhood. After clearance of acute infection,
herpesviruses enter a dormant state known as latency. Latency persists for the
life of the host and is presumed to be parasitic, as it leaves the individual at
risk for subsequent viral reactivation and disease. Here we show that herpesvirus latency also
confers a surprising benefit to the host. Mice latently infected with either
murine gammaerpesvirus 68 or murine cytomegalovirus, which are genetically
highly similar to the human pathogens Epstein–Barr virus and human
cytomegalovirus, respectively, are resistant to infection with
the bacterial pathogens
Listeria monocytogenes and
Yersinia pestis. Latency-induced protection is not
antigen specific but involves prolonged production of the antiviral cytokine
interferon-gamma and
systemic activation of macrophages. Latency thereby upregulates the basal
activation state of innate immunity against subsequent infections. We speculate
that herpesvirus latency may also sculpt the immune response to self and
environmental antigens through establishment of a polarized cytokine
environment. Thus, whereas the immune evasion capabilities and lifelong
persistence of herpesviruses are commonly viewed as solely pathogenic, our data
suggest that latency is a symbiotic relationship with immune benefits for the
host.