Virological and pathological features of mice infected with murine gammaherpesvirus 68

TLDR

Intranasal inoculation of MHV‑68 primarily infects the lung, targeting alveolar epithelium and mononuclear cells. The study examined primary MHV‑68 infection in BALB/c mice and proposed the model as a tool for investigating natural gamma‑herpesvirus infections in humans and animals. The infection was productive for 10 days, with viral DNA detectable up to 30 days and persisting latently in the spleen up to 90 days; lymphoproliferative lesions and germinal centers appeared in the lung, and virus was recovered from heart, kidney, adrenal gland, and spleen, while sick animals showed thymus and spleen atrophy and asymptomatic animals displayed splenomegaly, mirroring the pattern seen in human infectious mononucleosis.

Abstract

The primary infection of BALB/c mice with murine herpesvirus 68 (MHV-68) was investigated. When the virus was introduced intranasally, the lung was the main tissue infected, the virus being associated with alveolar epithelium and mononuclear cells. A productive infection lasted for 10 days, after which viral DNA could be detected by in situ hybridization up to 30 days after infection. At that time lymphoproliferative accumulations were also observed in the lung, with formation of germinal centres. Virus could also be recovered from the heart, kidney, adrenal gland and spleen during the primary infection. In addition, the spleen appeared to be the major site of virus persistence, with latently infected cells detected up to 90 days post-infection. During the primary infection, there was atrophy of the thymus and spleen of clinically sick animals. In contrast, lymphoproliferative responses, typified by splenomegaly, were frequently seen in asymptomatic animals. The pattern of infection observed in MHV-68-infected mice is similar to that seen in infectious mononucleosis of man following Epstein–Barr virus infection. The model described in this paper may prove to be useful in studying natural gamma-herpesvirus infections of man and domestic animals.