Abstract
Development of a vaccine against congenital infection with human cytomegalovirus is complicated by the issue of re-infection, with subsequent vertical transmission, in women with pre-conception immunity to the virus. The study of experimental therapeutic prevention of re-infection would ideally be undertaken in a small animal model, such as the guinea pig cytomegalovirus (GPCMV) model, prior to human clinical trials. However, the ability to model re-infection in the GPCMV model has been limited by availability of only one strain of virus, the 22122 strain, isolated in 1957. In this report, we describe the isolation of a new GPCMV strain, the CIDMTR strain. This strain demonstrated morphological characteristics of a typical Herpesvirinae by electron microscopy. Illumina and PacBio sequencing demonstrated a genome of 232,778 nt. Novel open reading frames ORFs not found in reference strain 22122 included an additional MHC Class I homolog near the right genome terminus. The CIDMTR strain was capable of dissemination in immune compromised guinea pigs, and was found to be capable of congenital transmission in GPCMV-immune dams previously infected with salivary gland‑adapted strain 22122 virus. The availability of a new GPCMV strain should facilitate study of re-infection in this small animal model.
Highlights
Development of a vaccine against human cytomegalovirus (HCMV) is a major public health priority [1]
The availability of a second strain of guinea pig cytomegalovirus (GPCMV) should enable the study of re-infection and, potentially, the development of vaccine strategies designed to protect against maternal re-infection in the guinea pig model of congenital cytomegalovirus infection
This further implies that despite potential bottlenecks imposed by selective breeding, GPCMV, as it exists within commercial breeding colonies, exhibits significant strain diversity of a nature similar to that of HCMV
Summary
Development of a vaccine against human cytomegalovirus (HCMV) is a major public health priority [1]. A number of recent studies have described fetal HCMV transmission in women with preconception immunity, due to re-infection with new strains of HCMV [7,8,9,10,11,12] Such infections can produce sequelae identical to those observed in congenitally infected infants born to women with primary HCMV infection in pregnancy [13,14]. Seven of 40 (17.5%) study women, but only 5 of 109 (4.6%) controls acquired antibodies reactive with new HCMV strains during pregnancy (p = 0.002), suggesting that maternal reinfection by new strains of HCMV is a major source of congenital infection in this population. The availability of a second strain of GPCMV should enable the study of re-infection and, potentially, the development of vaccine strategies designed to protect against maternal re-infection in the guinea pig model of congenital cytomegalovirus infection
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