New insight into widespread virus behind birth defects

April 12, 2018 by Anna Williams, Northwestern University
An artistically adapted confocal image of HCMV-infected fibroblast cells fixed at seven days post-infection and stained for acetylated microtubules (lower light blue strokes), the viral assembly compartment (magenta staining, glycoprotein B) and the host nucleus (upper turquoise region, DNA stain Hoechst). The image appeared on the cover of the journal Developmental Cell. Credit: Northwestern University

A Northwestern Medicine study published in Developmental Cell provides new insights into how cytomegalovirus—a common virus in the herpes family—replicates within human cells, and identifies proteins that may be therapeutically targeted to suppress infection.

Human cytomegalovirus (HCMV) is widespread around the world, infecting between 60 to 100 percent of all adults. There is currently no cure or vaccine for HCMV; once infected, people carry the virus for life.

Although HCMV typically does not cause any symptoms in healthy adults, the virus can be life-threatening for people with weakened immune systems or babies infected before birth. In fact, HCMV is the leading cause of and can result in long-term health problems, including hearing loss, small head size, vision impairment and developmental delay.

"HCMV has been described as a 'silent global burden' because it is so widespread, yet people remain largely unaware of its effects on the fetus and on child development," said principal investigator Derek Walsh, Ph.D., associate professor of Microbiology-Immunology.

Previous research has shown that during the viral replication process, HCMV forms a unique structure in the cytoplasm of called the assembly compartment (AC), where viral particles mature. Little was known, however, about how this structure behaves or functions during infection.

In the current study, the scientists developed new multi-color live cell imaging approaches in order to study the AC in living cells, in real-time. Their findings revealed that the compartment is highly dynamic and acts as a novel form of microtubule organizing center that allows the virus to remodel the host cell. In order to do so, it takes control of specialized microtubule regulatory proteins.

In collaboration with scientists at the University of Illinois at Chicago, the team also developed small peptides that target such and block the process of infection—with potential implications for the development of antiviral drugs in the future.

"This is an attractive option, as targeting specialized host proteins rather than evolutionarily adaptable viral proteins avoids the emergence of drug-resistant strains," Walsh explained.

The authors note that beyond just advancing understanding of how HCMV replicates and identifying new therapeutic targets, the study also provided new insights into how microtubules are regulated and function in the cell.

In future research, the scientists intend to continue to use HCMV as a model system to understand microtubule regulation within the cell and how this benefits the virus, as well as further investigate whether the small peptides developed in the study might have therapeutic benefit.

Dean Procter, Ph.D., a postdoctoral fellow in Walsh's laboratory, was the first author of the study.

The study was the featured paper in the latest issue of Developmental Cell and appeared on its cover. It also includes time-lapse images of HCMV infection. "I enjoy generating data that captivates the audience and ignites an inquisitive spark. I think our live-cell movies of HCMV assembly compartment maturation and nuclear rotation do just that," Procter said.

Explore further: Scientists ID human protein essential for human cytomegalovirus replication

More information: Dean J. Procter et al. The HCMV Assembly Compartment Is a Dynamic Golgi-Derived MTOC that Controls Nuclear Rotation and Virus Spread, Developmental Cell (2018). DOI: 10.1016/j.devcel.2018.03.010

Related Stories

Scientists ID human protein essential for human cytomegalovirus replication

May 11, 2017
Scientists have demonstrated that a human protein known as valosin containing protein (VCP) is essential for replication of human cytomegalovirus (HCMV). The findings, published in PLOS Pathogens, identify VCP as a potential ...

A common virus may help inform treatment planning for stem cell transplant patients

December 7, 2017
Most healthy people barely notice infection with the human cytomegalovirus (hCMV), a form of the herpes virus that has evolved with humans over thousands of years and usually lays dormant in the body after initial infection. ...

Proteins expressed by human cytomegalovirus mapped

November 23, 2012
(Medical Xpress)—A new study in the US and Germany has added to our understanding of the human cytomegalovirus (HCMV) and how it manipulates the cells it infects.

What viruses do to neuronal stem cells—effects of congenital transmission

April 14, 2016
Congenital transmission (from mother to unborn child) of viruses can cause abnormal brain development in the fetus. Examples of viruses that can pass through the placenta and into the fetal brain include cytomegalovirus, ...

Purging a virus from organ transplants

April 7, 2015
Human cytomegalovirus (HCMV) is an extremely common virus, which as other members of the herpes virus family causes life-long infections in humans. Most individuals are exposed to HCMV during childhood, yet symptoms can be ...

Recommended for you

Deadly Rift Valley fever: New insight, and hope for the future

July 19, 2018
Health control measures alone could be ineffective in the long term fight against the deadly Rift Valley fever which affects both humans and animals, a new study in the journal PNAS reports.

New guidelines to diagnose, manage rare endocrine disorders

July 19, 2018
International guidelines have been published for the first time to help doctors around the globe diagnose and manage patients with a very rare set of endocrine diseases known as pseudohypoparathyroidism and its related disorders, ...

Overuse of antibiotics not what the doctor ordered

July 19, 2018
With increased use of antibiotics worldwide linked to growing antibiotic resistance, a world-first study co-authored by a QUT researcher has highlighted the growing impact of non-prescription supply of antibiotics in community ...

Alcohol-related cirrhosis deaths skyrocket in young adults

July 18, 2018
Deaths from cirrhosis rose in all but one state between 1999-2016, with increases seen most often among young adults, a new study shows.

Hidden blood in feces may signal deadly conditions

July 17, 2018
(HealthDay)—Even if it's not visible to the naked eye, blood in the stool can be serious—a sign of a potentially fatal disease other than colon cancer, new research suggests.

Childhood abuse linked to greater risk of endometriosis, study finds

July 17, 2018
Endometriosis, a painful condition that affects one in 10 reproductive-age women in the U.S., has been linked to childhood physical and sexual abuse, according to findings published today in the journal Human Reproduction.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.