Studies could impact the spread of Zika, treatments for RSV infections
and Crohn’s disease in children
[August 4, 2016; Philadelphia, PA] – Three new studies, facilitated by Penn Vet’s Center for Host-Microbial Interactions, could provide novel approaches for the prevention and treatment of viruses that impact both animals and humans. The studies will explore how microbes impact viral susceptibility, infection response, and infection predisposition.
The projects are funded by generous gifts from Robert and Hope Sheft and Jay Goldman.
“Thanks to the generosity of the Shefts and Mr. Goldman, the Center for Host-Microbial Interactions has facilitated cutting-edge, interdisciplinary research at Penn Vet,” said Center Director Dr. Christopher Hunter. “At a time when Zika and Ebola are issues of global concern, it is imperative that we better understand how viruses can influence health and disease. With the resources available through the Center, our researchers can actively study genomic approaches to improve the health of both animals and people.”
The role of the insect microbiome on viral susceptibility
Dr. Sara Cherry, Associate Professor of Microbiology, Perelman School of Medicine
Dr. Michael Povelones, Assistant Professor of Pathobiology, Penn Vet
Mosquitoes are vectors for many viruses that cause serious human disease, from Dengue fever to West Nile virus and Zika. For these diseases to be transmitted to humans, a mosquito must become infected, yet little is known about the factors that regulate this process. Recent work by Dr. Cherry in fruit flies – a model insect – showed that the microbiome can help “prime” fruit flies to be resistant to infection with certain viruses. Recognizing Penn Vet’s expertise and resources in mosquito-transmitted diseases, Dr. Cherry is collaborating with Dr. Povelones to address this question in mosquitoes. Understanding the details of the natural mosquito defense system could elucidate novel strategies for controlling the spread of viruses by insect vectors, and more broadly inform our understanding of how normal gut bacteria protect animals and humans from infection by pathogens.
The role of defective viral genomes on infection response
Dr. Carolina Lopez, Associate Professor of Microbiology and Immunology, Penn Vet
Research has shown that some viruses make defective copies of themselves, known as defective viral genomes (DVGs). No longer just lab anomalies, DVGs have been found in infections in people. In particular, DVGs have been found in nasopharyngeal samples of children infected with Respiratory Syncytial Virus (RSV), a leading cause of severe respiratory illness in children. There is no way to predict the outcome of an RSV infection, which could range from a mild respiratory illness to death, nor are there approved vaccines to prevent infection.
DVGs have proven to be good at priming the immune system. In mice with RSV infections, the presence of a high content of DVGs resulted in reduced disease severity and faster viral clearance. Dr. Lopez postulates that the presence of specific immunostimulatory DVGs during respiratory viral infections can lead to viral clearance and full disease recovery in humans.
Because many different DVGs are generated during an infection and not all DVGs are equally immunostimulatory, Dr. Lopez will work to better understand the RNA sequences of immunostimulatory DVGs that occur in patients. Working with samples from the Children’s Hospital of Philadelphia (CHOP), she will sequence DVGs from patients infected with RSV to identify the predominant species that stimulate the immune response. Her findings could eventually be used to develop a method to predict the speed of virus control and the clinical outcome of common respiratory viral infections.
The impact of MAP on the gut microbiome of calves
Dr. Marie-Eve Fecteau, Associate Professor of Food Animal Medicine and Surgery
Dr. Raymond Sweeney, Professor of Medicine
Johne's disease (JD) is a widespread chronic gastrointestinal disease of cattle caused by a bacterial infection with Mycobacterium avium subsp. paratuberculosis (MAP). MAP infections result in inflammation of the intestinal lining, chronic diarrhea, weight loss, and death. Currently, no drugs are approved for the prevention or treatment of JD in cattle in the U.S., and vaccination is not fully protective. Nearly 90% of all U.S. dairy herds have MAP-infected cattle, costing producers hundreds of millions of dollars. But the impact of MAP on the gut microbiome of calves has never before been studied. The aim of this study is to identify bacterial genes that could have a role in modulating the intestinal inflammatory response.
Drs. Fecteau and Sweeney have demonstrated that fecal bacterial communities of MAP-positive cows varied significantly from their exposed and MAP-negative herdmates. These findings are similar to the gastrointestinal microbial imbalance demonstrated in human patients suffering from IBD, particularly Crohn’s disease. The parallels in disease progression and pathology between Johne’s disease and human Crohn’s disease, taken together with the high prevalence of MAP in the environment, have prompted collaboration between Penn Vet and CHOP’s Division of Gastroenterology, Hepatology, and Nutrition. The interdisciplinary team of veterinary microbiologists, large animal veterinarians, and pediatric gastroenterologists will be well positioned to determine whether MAP could be involved in a subset of Crohn’s disease in humans, potentially leading to new diagnostic and treatment approaches for intestinal disease in both animals and humans.
CHOP has generously provided support to fund this study.
About the Center for Host-Microbial Interactions
The Center for Host-Microbial Interactions is designed to facilitate collaborative projects that leverage genomics to study the intersection of microbes and disease. In doing so, researchers gain insight into how bacteria, parasites, viruses, and other organisms interact with their animal and human hosts in ways that either maintain health or lead to disease. Each year, the Center invites researchers to submit proposals for funding. Additionally, the Center provides ongoing support and training for Penn Vet faculty and their labs to carry out analyses of the complex datasets generated by genomic approaches. For more information about the Center, click here.