A Review of Murine Cytomegalovirus as a Model for Human Cytomegalovirus Disease—Do Mice Lie?

Abstract

Since murine cytomegalovirus (MCMV) was first described in 1954, it has been used to model human cytomegalovirus (HCMV) diseases. MCMV is a natural pathogen of mice that is present in wild mice populations and has been associated with diseases such as myocarditis. The species-specific nature of HCMV restricts most research to cell culture-based studies or to the investigation of non-invasive clinical samples, which may not be ideal for the study of disseminated disease. Initial MCMV research used a salivary gland-propagated virus administered via different routes of inoculation into a variety of mouse strains. This revealed that the genetic background of the laboratory mice affected the severity of disease and altered the extent of subsequent pathology. The advent of genetically modified mice and viruses has allowed new aspects of disease to be modeled and the opportunistic nature of HCMV infection to be confirmed. This review describes the different ways that MCMV has been used to model HCMV diseases and explores the continuing difficulty faced by researchers attempting to model HCMV congenital cytomegalovirus disease using the mouse model.

Advances in Model Systems for Human Cytomegalovirus Latency and Reactivation

“…The strict cellular tropism of HCMV has long been a barrier in understanding viral latency and reactivation in vivo . While murine CMV and rat CMV have served as surrogates for in vivo studies, they differ substantially from HCMV in their genome organization ( 90 ). For instance, they lack homologs of the UL133-138 locus and the RL11 gene UL7, which have been shown to play critical roles during different stages of viral latency and reactivation ( 20 , 27 , 91 – 95 ).…”

Epigenetic regulation of natural killer cell memory*

“…Several aspects of human CMV (HCMV) can be recapitulated in the mouse system using mouse CMV (MCMV), which has proven to be instrumental in unveiling many mechanisms of host responses. 24 CMV exposure can initiate an acute systemic infection, affecting such organs as the spleen, liver, lung, and salivary glands. Upon resolution, CMV becomes latent in most peripheral organs where virions cannot be detected, with the exception of the salivary gland, where it becomes locally persistent.…”

Immune Prophylaxis and Therapy for Human Cytomegalovirus Infection

“…Mouse CMV (MCMV) is another model virus that has been widely used to investigate HCMV infection and disease. The utility and limitations of this model have been recently reviewed [36], so we will not describe this model in detail. We will, however, draw attention to recent developments with humanized mouse models that contain a functional cellular and humoral human immune system (HIS) [37].…”