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

December 7, 2017, Virginia Commonwealth University

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. Now, in a study recently published in the journal PLOS ONE, a team of scientists from VCU Massey Cancer Center have shown a genetic relationship between the reactivation of hCMV and the onset of graft-versus-host disease (GVHD), a potentially deadly condition in which the immune system attacks healthy tissue following a bone marrow or stem cell transplant.

This new finding is the latest in a line of research led by physician-scientist, Amir Toor, M.D. Toor and his colleagues have been working to create computer models that simulate immune system recovery following stem cell transplantation in hopes of reducing complications such as GVHD and making transplantation an option for more patients. While the relationship between GVHD and hCMV has been described in medical literature since the 1980s, the connection was not well understood until one of Toor's mentees, Charles Hall, M.S., showed genetic similarities between the virus and tissue expressing GVHD.

"Until now, physicians have taken a 'wait and see' approach to antiviral therapies following transplantation," says Toor, a hematologist-oncologist in the Bone Marrow Transplant Program and member of the Developmental Therapeutics research program at VCU Massey Cancer Center as well as professor in the Division of Hematology, Oncology and Palliative Care at the VCU School of Medicine. "But, based on our data, we believe there is a case for early intervention with personalized antiviral treatments following stem cell transplantation in order to suppress hCMV reactivation."

Toor and his team sequenced the DNA of 77 stem cell donors and their recipients. They found a significant number of patients (18) experienced hCMV reactivation and GVHD, and a majority (13) of those patients experienced hCMV reactivation prior to GVHD onset. Using the information they uncovered through DNA sequencing along with data from a new database established by the Center for the Study of Biological Complexity at VCU called Cross Reactive Open Source Sequence Database, developed by Charles Hall, M.S., and Vishal Koparde, Ph.D., the team uncovered a novel connection between the virus and GVHD.

The scientists found similarities in HLA-bound peptide sequences between human and hCMV genomes. The HLA (human leukocyte antigen) is a system of genes responsible for regulating immune responses, and peptides are short chains of amino acids that play key roles in regulating the activities of other molecules. It turns out that hCMV peptides are very similar to peptides expressed in GVHD-affected tissue.

"We developed a computer model that shows how the immune system can react to hCMV peptides to trigger a graft-versus-host response," explained Toor. "By sequencing the DNA of stem cell donors and recipients, we believe we can use computer modeling to further identify patients at risk and better personalize post-transplant care to decrease the potential for graft-versus-host disease."

Toor hopes to further explore the relationship between hCMV and GVHD. His team is currently working to secure funding to apply their model to larger patient data sets.

Explore further: Researchers identify patients at risk for stem cell transplant complications

More information: Charles E. Hall et al. Sequence homology between HLA-bound cytomegalovirus and human peptides: A potential trigger for alloreactivity, PLOS ONE (2017). DOI: 10.1371/journal.pone.0178763

Related Stories

Researchers identify patients at risk for stem cell transplant complications

June 8, 2015
Researchers at VCU Massey Cancer Center's Bone Marrow Transplant Program have recently published findings from a phase 2 clinical trial that demonstrate lymphocyte recovery in related and unrelated stem cell transplant recipients ...

Antibodies from rabbits improve survival and relapse outcomes of leukemia and myelodysplasia

July 6, 2012
Researchers at Virginia Commonwealth University (VCU) Massey Cancer Center's Bone Marrow Transplant Program have demonstrated that the use of antibodies derived from rabbits can improve the survival and relapse outcomes of ...

Depletion of naive T cells from stem cell grafts limits chronic graft-versus host disease

June 8, 2015
Stem cell transplantation is used to treat hematologic malignancies, such as leukemia. Patients that receive donor cells are at risk of developing graft-versus host disease (GVHD). This potentially fatal complication results ...

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 ...

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 ...

New test helps guide treatment for bone marrow transplant patients with graft vs. host disease

January 13, 2015
A new test can guide treatment for patients with graft versus host disease (GVHD), an often life-threatening complication of bone marrow and stem cell transplants, according to research from the University of Michigan published ...

Recommended for you

New findings cast light on lymphatic system, key player in human health

October 16, 2018
Scientists at the Oklahoma Medical Research Foundation have broken new ground in understanding how the lymphatic system works, potentially opening the door for future therapies.

Age-related increase in estrogen may cause common men's hernia

October 16, 2018
An age-related increase in estrogen may be the culprit behind inguinal hernias, a condition common among elderly men that often requires corrective surgery, according to a Northwestern Medicine study was published Oct. 15 ...

New model suggests cuffless, non-invasive blood pressure monitoring possible using pulse waves

October 16, 2018
A large team of researchers from several institutions in China and the U.S. has developed a model that suggests it should be possible to create a cuffless, non-invasive blood pressure monitor based on measuring pulse waves. ...

Discovery of inner ear function may improve diagnosis of hearing impairment

October 15, 2018
Results from a research study published in Nature Communications show how the inner ear processes speech, something that has until now been unknown. The authors of the report include researchers from Linköping University, ...

Widespread errors in 'proofreading' cause inherited blindness

October 12, 2018
Mistakes in "proofreading" the genetic code of retinal cells is the cause of a form of inherited blindness, retinitis pigmentosa (RP) caused by mutations in splicing factors.

Team's study reveals hidden lives of medical biomarkers

October 12, 2018
What do medical biomarkers do on evenings and weekends, when they might be considered off the clock?

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.