Murine Gammaherpesvirus 68: A Small Animal Model for Gammaherpesvirus-Associated Diseases

Abstract

Murine gammaherpesvirus 68 (MHV68) is a naturally occurring pathogen of murid rodents that is genetically related to the human gammaherpesviruses Epstein-Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV). Viral, immunologic, and disease parameters following experimental infection of laboratory mice with MHV68 closely resemble what occurs during primary EBV infection of humans, which suggests that MHV68 infection of mice offers a small animal model to study in general the pathogenesis of gammaherpesvirus infections. Diseases elicited by MHV68 infection include lymphoproliferative diseases, idiopathic pulmonary fibrosis, and autoimmune diseases, ailments also associated with EBV infection of humans. Furthermore, MHV68 infection also is linked to the development of vasculitis, encephalomyelitis, and other disorders that resemble pathologies with viral and nonviral etiologies in humans. This review aims to provide an overview of MHV68-associated diseases in infected mice that may provide a model for understanding basic mechanisms by which similar diseases in humans occur and can be treated.

More than just oncogenes: mechanisms of tumorigenesis by human viruses

“…Hence, while studies with murine polyomavirus have provided important insights into human carcinogenesis [12], this virus is not an appropriate animal model for MCPyV-mediated human carcinogenesis. For γ-herpesviruses, the murine herpesvirus 68 (MHV-68) is used to study acute infection in vivo , virus dissemination and development of latency [13]. Formation of tumors with this virus occurs in a minority of cases and only after nine months of infection, unless the infected mice are immunosuppressed due to genetic mutations or drug treatment [14].…”

An endothelial cell line infected by Kaposi’s sarcoma–associated herpes virus (KSHV) allows the investigation of Kaposi’s sarcoma and the validation of novel viral inhibitors in vitro and in vivo

“…Murine gamma-2 herpesvirus 68 (MHV-68) was proposed as a model to mimic KSHV infection in the mouse [14]. Similarly to KSHV it establishes latent infection in B cells, which may lead to lymphoproliferative pathology [15,16]. However, MHV-68 fails to establish tumors of endothelial origin and therefore cannot be used as a small animal model for Kaposi's sarcoma.…”

Recombinant IFN-γ from the bank vole Myodes glareolus: a novel tool for research on rodent reservoirs of zoonotic pathogens

“…Voles are also a natural reservoir for the murid herpesvirus 4. Isolates of it (MHV-68) serve as models for human gammaherpesviruses 64 and IFN-γ is known to control gene expression during MHV-68 latency in vivo in mice 65 . However, previous studies have pointed out various differences in pathogenesis between lab mice and natural hosts like A .…”