Abstract
Recent reports suggested that chronic herpesvirus infection, as a constituent of the so-called virome, may not only exert harmful effects but may also be beneficial to the host, for example mediating increased resistance to secondary infections or to tumors. To further challenge this concept, specifically regarding increased resistance to tumors, we infected chimeric HLA-DR4-H2-E (DR4) mice, a mouse strain which spontaneously develops hematological tumors, with the rodent herpesvirus murine gammaherpesvirus 68 (MHV-68). Using this model, we observed that infection with wildtype MHV-68 completely prevented tumor formation. This happened, however, at the cost of hyposplenism. In contrast to wildtype infection, infection with a latency-deficient mutant of MHV-68 neither prevented tumor formation nor induced hyposplenism. The underlying mechanisms are not known but might be related to an infection-mediated priming of the immune response, resulting in the suppression of a tumor promoting endogenous retrovirus. Thus, under certain circumstances, chronic herpesvirus infection may prevent the development of tumors.
Highlights
Herpesviruses are broadly recognized as important pathogens, causing a variety of diseases in humans and in other species
When we analyzed the mice with regard to the development of tumors [10], we observed that infection with wt murine gammaherpesvirus 68 (MHV-68) completely prevented tumor formation (Fig 1A)
Using chimeric HLA-DR4-H2-E (DR4) mice that spontaneously develop diverse hematological malignancies starting around eight months of age, we demonstrate that infection with wt MHV-68 completely prevented tumor formation, albeit at the cost of hyposplenism
Summary
Herpesviruses are broadly recognized as important pathogens, causing a variety of diseases in humans and in other species. Since herpesviruses establish a lifelong chronic infection and are present in almost every individual, yet cause disease in only a limited number of predisposed individuals, they are considered to be part of the so-called virome [3,4] This new and emerging concept includes the view that herpesviruses, as constituents of the virome, may exert harmful effects but may be beneficial to the host [4]. Evidence to support this hypothesis comes, for example, from experimental infection of mice with a gammaherpesvirus called murine gammaherpesvirus 68 (MHV-68), which serves as a small animal model to investigate gammaherpesvirus pathogenesis [5]. Barton et al demonstrated that chronic infection of mice with a gammaherpesvirus increased
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