Abstract

BackgroundCytomegalovirus (CMV) congenital infection is the major viral cause of well-documented birth defects in human. Because CMV is species-specific, the main obstacle to developing animal models for congenital infection is the difference in placental architecture, which preludes virus transmission across the placenta. The rat placenta, resembling histologically to that of human, could therefore facilitate the study of CMV congenital infection in human.ResultsIn this report, we present clear evidences of the transplacental property of a new rat CMV (RCMV), namely ALL-03, which had been isolated from placenta and uterus of the house rat. Our study signifies the detection of infectious virus, virus particles, viral protein and DNA as well as immune response to demonstrate a natural model of acute CMV infection including the immunocompetent and immunocompromised host associated with or without pregnancy. It is characterized by a full range of CMV related clinical signs; lesions and anatomical virus distribution to uterus, placenta, embryo, fetus, neonate, lung, kidney, spleen, liver and salivary gland of the infected rats in addition to the virus-specific seroconversion. The preference of the virus for different organs mimics the situation in immunocompromised man. Most interestingly, the placenta was observed to be involved in the maternofetal infection and hence confirmed the hypothesis that the RCMV strain ALL-03 is capable to cross the placenta and infect the offsprings congenitally.ConclusionThe maternal viremia leading to uterine infection which subsequently infecting to the fetus through the placenta is the most likely phenomenon of CMV vertical transmission in our study.

Highlights

  • Cytomegalovirus (CMV) congenital infection is the major viral cause of welldocumented birth defects in human

  • guinea pig CMV (GPCMV) provides a well-characterized model of transplacental viral infection, studies in this system have been hampered by a lack of genetic knowledge of the animal itself

  • We demonstrate a natural model of acute rat CMV (RCMV) infection, which includes the characteristic organ distribution of RCMV in male rats and female rats with or without pregnancy as well as the immune response to the infection

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Summary

Introduction

Cytomegalovirus (CMV) congenital infection is the major viral cause of welldocumented birth defects in human. The expenses of the primates and pigs, as well as the rarity of their CMV seronegative animals make these models impractical for large-scale vaccine studies For these reasons, rats, mice, and guinea pigs came into favor because of their small size, low cost, short life span, ease of handling and high reproductive rate. Rats, mice, and guinea pigs came into favor because of their small size, low cost, short life span, ease of handling and high reproductive rate These CMVs (RCMV, MCMV and GPCMV) closely resemble HCMV. The rat system is a significant advance on the guinea pig or mouse model for studying various aspects of viral pathogenesis, the effect of therapeutic intervention as well as the evaluation of vaccine candidates for CMV congenital infection in humans

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