What We Have Learned from Animal Models of HCMV

Abstract

Although human cytomegalovirus (HCMV) primary infection is generally asymptomatic, in immune-compromised patients HCMV increases morbidity and mortality. As a member of the betaherpesvirus family, in vivo studies of HCMV are limited due to its species specificity. CMVs from other species are often used as surrogates to express HCMV genes/proteins or used as models for inferring HCMV protein function in humans. Using innovative experiments, these animal models have answered important questions about CMV's life cycle, dissemination, pathogenesis, immune evasion, and host immune response. This chapter provides CMV biologists with an overview of the insights gained using these animal models. Subsequent chapters will provide details of the specifics of the experimental methods developed for each of the animal models discussed here.

Comparison of monovalent glycoprotein B with bivalent gB/pp65 (GP83) vaccine for congenital cytomegalovirus infection in a guinea pig model: Inclusion of GP83 reduces gB antibody response but both vaccine approaches provide equivalent protection against pup mortality

“…Small animal models for the study of CMV vaccines require use of the strain unique to that specific species[13, 14]. Guinea pigs provide a particularly valuable model for study of vaccines against congenital infection, since the guinea pig CMV (GPCMV) is able to cross the placenta and cause congenital infection[15-19].…”

Repair of a Mutation Disrupting the Guinea Pig Cytomegalovirus Pentameric Complex Acquired during Fibroblast Passage Restores Pathogenesis in Immune-Suppressed Guinea Pigs and in the Context of Congenital Infection

“…Preclinical modeling of vaccines against congenital infection must rely on the study of species-specific CMVs, since HCMV will not infect nonhuman cells (3,4). The study of guinea pig cytomegalovirus (GPCMV) is particularly valuable, since this virus will cross the placenta and infect pups in utero, leading to congenital transmission (5).…”

There's Always Another Way! Cytomegalovirus’ Multifaceted Dissemination Schemes

“…Predominantly mouse CMV (MCMV) has been used to draw conclusion about CMV dissemination. The mouse model is appealing for studying dissemination because MCMV has similar infection and pathogenesis to HCMV [101], MCMV contains homologues and/or orthologues of many HCMV genes, the mouse has a well-characterized immune system, and there are numerous reagents available including transgenic and knockout mice [102].…”