PUBLIC RELEASE DATE:

30-Oct-2013

Contact: Jim Fessenden james.fessenden@umassmed.edu 508-856-2000 University of Massachusetts Medical School

WORCESTER, MA New insights into how human cytomegalovirus (CMV), the leading cause of birth defects associated with infection spreads from pregnant mother to fetus and from organ to organ in newborns provides translational researchers an exciting new avenue for investigation that may lead to the development of therapeutic interventions. Using next generation sequencing and population genetic modeling, scientists at the University of Massachusetts Medical School (UMMS) and the Ecole Polytechnique Fdrale de Lausanne (EPFL) have found that CMV evolves rapidly and dramatically in humans. These findings, published in PLoS Genetics, provide new genetic targets that could impede the evolution of CMV and prevent its spread.

"These findings have important implications for how we think about and develop new therapeutic treatments for CMV," said Timothy F. Kowalik, PhD, associate professor of microbiology and physiological systems and senior author of the study. "Although CMV is able to infect a wide variety of organs throughout the body, there are a substantial number of genetic changes that occur before the virus can spread and replicate efficiently in different anatomic niches. If these genetic changes can be prevented, it may be possible to isolate and block the spread of CMV."

CMV is a ubiquitous virus that infects most of the human population and can move throughout the body from organ to organ. Infection is usually asymptomatic in healthy hosts, but may cause severe symptoms for patients with a compromised immune system, such as organ transplant recipients, HIV-infected persons, newborn infants or the fetus during gestation.

Congenital CMV infection, which is passed from a pregnant mother to fetus, is a significant cause of birth defects, and remains a high priority for vaccine development according to the nonprofit, Institute of Medicine. An estimated 30,000 infants per year in the U.S. are diagnosed with congenital CMV infection, and nearly 20 percent exhibit permanent neurologic effects such as hearing loss or developmental delay.

To better understand how CMV evolves in fetuses and newborns during symptomatic congenital infection, researchers at UMMS and the University of Minnesota Medical School collected samples from the plasma and urine of five congenitally infected infants during the first year after birth. Using next generation DNA sequencing, Kowalik and colleagues studied the diversity and changes in viral DNA sequences over time and between organs. Though the DNA sequences from viruses taken from the same type of sample (e.g. plasma) were similar to each other, the study's authors found dramatic differences between the sequences collected from viruses in the plasma and urine of the same infant. Surprisingly, the plasma and urine sequences from the same infant were as different as sequences from two unrelated infants.

These results suggest that CMV is able to evolve very quickly as the differences between the plasma and urine sequences likely occurred in the short period between the initial, in utero infection, and the first year after birth. However, the mechanism driving this phenomenon remained unclear.

To answer this question, researchers used mathematical modeling and statistical inference to uncover evidence that population bottlenecks and expansions may play a significant role in the virus' evolution after infection. Characterized by a substantial reduction in viral copies followed by a quick rebound, population bottlenecks and expansions can lead to dramatic changes in DNA sequences that result in two related populations quickly becoming dissimilar. In the case of CMV infection, this phenomenon appeared to coincide with the virus moving from the mother to the fetus and later migrating from the plasma to the kidneys.

Originally posted here:
Research points to potential window for treating CMV and preventing mother-to-child transmission

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