Zika Virus: An unlikely hero?

“Only time and peer-reviewed research will tell,” says Dr. Verma

Dr. Verma and his team

Dr. Verma and his team (from left to right): Kammi Dingman, Samantha Solomon, Namrata Gupta, Timsy Uppal, Prerna Dabral, Roxanne Strahan, Majid Khan and Subhash Verma, Ph.D.

Zika virus (ZIKV) made international headlines just before the 2016 Summer Olympics in Brazil when a South American epidemic was reported after alarming rates of infants were born with abnormal brain development, resulting in small heads, also known as microcephaly.

Ever since, ZIKV has rapidly become a hot research subject for investigators across the world.

One such study quickly garnered national attention with its claim, "Zika virus kills brain cancer stem cells." Researchers out of Washington University School of Medicine in St. Louis and the University of California San Diego School of Medicine hypothesized that ZIKV could be used as an oncolytic virus to kill glioblastoma stem cells (GSCs) in the brain and published their findings in the Journal of Experimental Medicine on September 5, 2017.

Glioblastoma is the most prevalent and aggressive form of brain tumor. UNR Med Associate Professor in the department of Molecular Microbiology and Immunology Subhash C. Verma, Ph.D., explains, "Glioblastoma is a mixture of cells including the [GSCs], or tumor initiating cells, which have tumorigenic self-renewal capabilities, thus causing uncontrollable tumor growth." An estimated 12,000 people are diagnosed in the United States each year, recently including John McCain, U.S. Senator from Arizona. Treatment options, which usually involve a combination of surgery, radiation and chemotherapy, are limited and rarely successful in extending a patient's prognosis.

ZIKV belongs in the same family of deadly viruses such as West Nile virus, yellow fever and Dengue virus. The virus was originally discovered in non-human primates in the Ugandan Zika Forest in 1947. Since its discovery, only 14 human cases were thought to exist until a 2007 epidemiological study following an outbreak on Yap Island and the Federated States of Micronesia, where approximately 75 percent of the inhabitants were infected while few exhibited symptoms-mild fever, rash, joint pain and reddening of the eye.

Findings from the 2007 epidemiological study, in conjunction with the 2015 South America epidemic, led investigators to the conclusion that ZIKV most often affects growing neuronal cells, but not already grown, or differentiated, cells, resulting in newborns with microcephaly and adults—even pregnant mothers—with little to no symptoms.

The disparity in affected brains cells is what led authors of the glioblastoma study to the hypothesis that if ZIKV could induce neuronal cell death—also known as apoptosis—in a growing fetal brain, but not differentiated cells in a mature brain, perhaps the virus could similarly affect the growth of cancer-causing GSCs. While early results in mice and donor tissues are promising, Dr. Verma explains why there is still much to be done:

"ZIKV joins the list of already existing oncolytic viruses, including herpes simplex virus, adenovirus and poliovirus. There are several safety issues, including the host immune response triggered by the virus, which need to be addressed before it can be used therapeutically. Additionally, ZIKV was recently shown to induce apoptosis in neighboring non-infected neuronal cells."

Dr. Verma and his team at UNR Med are trying to bolster the medical community's understanding of ZIKV as their own research attempts to recognize how the virus enters the fetal brain, which is supposed to be protected from microorganisms by the transplacental barrier. Additionally, Dr. Verma's team is working towards preventing microcephaly by evaluating the effects of virus replication in various cells, including monocytes and neuronal cells, to ultimately block apoptosis and inflammation.


Contact

Julie Ardito
Senior Director, Advancement and Engagement
Office: (775) 784-6006
jardito@med.unr.edu

The University of Nevada, Reno School of Medicine is a community-based, research-intensive medical school with a statewide vision that has served Nevada for more than 48 years as its first public medical school. UNR Med's vision is a healthy Nevada, supported by our mission: establishing excellence in medical education, medical care, research and community engagement, while committing to a culture of respect, compassion and inclusion. Through targeted growth and investment in research, clinical services, education and outreach, UNR Med is a resource for improving healthcare regionally and across the country. For more information, visit: med.unr.edu.