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9/26/2014  |   4:30 PM - 6:00 PM   |  

Maternal CD4+ T cells play an important role in determining fetal outcome following congenital cytomegalovirus infection in the rhesus macaque model of transplacental cytomegalovirus transmission

Transplacental transmission of human cytomegalovirus (CMV) is the leading infectious cause of sensorineural hearing loss (SNHL) and brain damage in infants worldwide. Each year, approximately 40,000 infants are affected in the U.S, of which 20% are born with or develop CMV-associated sequelae. Protection against congenital CMV transmission is thought to be provided in part by components of the maternal immune response elicited through natural HCMV infection as infants born to HCMV-seropositive women have low frequency and severity of congenital disease. Identification of the protective immune correlates has been hindered by lack of a relevant large animal model. We report for the first time, primary congenital CMV transmission in nonhuman primates and a role for CD4+ T cells in determining fetal outcome. Four rhesus CMV (RhCMV)-seronegative pregnant females were inoculated intravenously during first trimester with RhCMV one week after administration of an anti-CD4+ T cell antibody. Three additional rhCMV-seronegative non-CD4+ T cell-depleted, immunocompetent females were infected at a similar gestational time point. In the CD4+ T cell-depleted group, three females underwent spontaneous abortion, whereas the fourth advanced to full-term. Within the immunocompetent group, all pregnancies were carried to full-term. A third group including three RhCMV-seropositive, CD4+ T cell-depleted females also carried their infants to term, indicating RhCMV infection and not CD4+ T cell-depletion caused high abortion rates. Congenital RhCMV infection in the CD4+ T cell-depleted group was confirmed by detection of RhCMV in two aborted fetuses using qPCR in addition to signs of neutropenia and RhCMV DNA in the saliva and urine of the surviving infant. Altogether these data suggest an important role for CD4+ T cells in determining fetal outcome of primary maternal CMV infection. Our nonhuman primate model for congenital CMV transmission provides a critical tool for future studies aimed at testing vaccines that protect against congenital CMV transmission.

Kristy Bialas (Primary Presenter), Kristy.Bialas@dm.duke.edu;
I am a trained virologist with a specific interest in viral transmission and pathogenesis. I received my Bachelors of Science degree from Gettysburg College and my Masters of Science and PhD in Virology from the University of Rochester School of Medicine and Dentistry. Previously, I studied influenza virus morphology and the effect morphology has on the efficiency of viral spread in vitro. Currently, my research as a post-doctorate scholar at the Duke Human Vaccine Institute focuses on the identification of unique genomic characteristics of congenitally transmitted CMV founder virus populations, as well as characterization of the maternal immune factors which influence the rate of congenital infection and disease severity of CMV-infected infants. The Permar laboratory has recently developed a nonhuman primate model of congenital CMV transmission for this purpose

ASHA DISCLOSURE:

Financial - No relevant financial relationship exist.

Nonfinancial - No relevant nonfinancial relationship exist.

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