Featured Research

from universities, journals, and other organizations

Potential window for treating CMV, preventing mother-to-child transmission

Date:
October 30, 2013
Source:
University of Massachusetts Medical School
Summary:
Using next generation sequencing and population genetic modeling, scientists have found that CMV evolves rapidly and dramatically in humans. These findings provide new genetic targets that could impede the evolution of CMV and prevent its spread.

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 Fιdιrale 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.

Related Articles


"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.

The model also suggests that the timing of initial fetal infection in the patients was at 13 to 18 weeks gestational age, while viral spread from blood plasma to the kidneys occurred about 11 weeks later. "This timing," said Kowalik, "may provide an important window for treating CMV when it is most vulnerable and before it can evolve and spread."

Additional study showed that natural selection, the process through which certain advantageous biological traits become more common, results in as much as 20 percent of the viral genes changing as it moved from one biological niche to another. "Not surprisingly, the genes impacted by this selection process affect several viral functions involved in dissemination, including viral replication in distinct cell types and evasion of the host immune response, and are required to allow the virus to move to and replicate efficiently in different organs," said lead author of the study, Nicholas Renzette, PhD, a postdoctoral fellow at UMMS.

This new understanding of how CMV adapts and evolves after infection provides researchers with potential targets for treating the disease, said Kowalik. "This work shows that CMV infection spreads during a relatively small window during gestation, suggesting an opportunity for preventative treatments," he said. "Furthermore, the delay between initial fetal infection and dissemination to the kidneys, may present a window for stopping spread of the virus throughout the body, thereby preventing symptoms of infection, such as hearing loss."

The next step for Renzette, Kowalik and colleagues is to determine which genetic changes associated with immune responses to infection may be amendable to potential treatments.


Story Source:

The above story is based on materials provided by University of Massachusetts Medical School. Note: Materials may be edited for content and length.


Journal Reference:

  1. Nicholas Renzette, Laura Gibson, Bornali Bhattacharjee, Donna Fisher, Mark R. Schleiss, Jeffrey D. Jensen, Timothy F. Kowalik. Rapid Intrahost Evolution of Human Cytomegalovirus Is Shaped by Demography and Positive Selection. PLoS Genetics, 2013; 9 (9): e1003735 DOI: 10.1371/journal.pgen.1003735

Cite This Page:

University of Massachusetts Medical School. "Potential window for treating CMV, preventing mother-to-child transmission." ScienceDaily. ScienceDaily, 30 October 2013. <www.sciencedaily.com/releases/2013/10/131030125619.htm>.
University of Massachusetts Medical School. (2013, October 30). Potential window for treating CMV, preventing mother-to-child transmission. ScienceDaily. Retrieved April 25, 2015 from www.sciencedaily.com/releases/2013/10/131030125619.htm
University of Massachusetts Medical School. "Potential window for treating CMV, preventing mother-to-child transmission." ScienceDaily. www.sciencedaily.com/releases/2013/10/131030125619.htm (accessed April 25, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Saturday, April 25, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

85 Killed in Niger by Meningitis Since Start of Year

85 Killed in Niger by Meningitis Since Start of Year

AFP (Apr. 24, 2015) — A meningitis outbreak in Niger has killed 85 people since the start of the year prompting authorities to close schools in the capital Niamey until Monday. Video provided by AFP
Powered by NewsLook.com
C-Section Births a Trend in Brazil

C-Section Births a Trend in Brazil

AFP (Apr. 24, 2015) — More than half of Brazil&apos;s babies are born via cesarean section, as mothers and doctors opt for a faster and less painful experience despite the health risks. Duration: 02:02 Video provided by AFP
Powered by NewsLook.com
Anti-Malaria Jab Hope

Anti-Malaria Jab Hope

Reuters - News Video Online (Apr. 24, 2015) — The world&apos;s first anti-malaria vaccine could get the go-ahead for use in Africa from October if approved by international regulators. Paul Chapman reports. Video provided by Reuters
Powered by NewsLook.com
3D Food Printing: The Meal of the Future?

3D Food Printing: The Meal of the Future?

AP (Apr. 23, 2015) — Developers of 3D food printing hope the culinary technology will revolutionize the way we cook and eat. (April 23) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins