Zika virus: checking its progress and harnessing its power

Research scientists believe they have figured out how the Zika virus, which scourged Latin America in 2015-2016, can be fenced off from infecting brain cells and, even more extraordinary, used to help fight brain cancer.  One of the most devastating impacts of Zika virus infection is microcephaly—a condition where babies of infected mothers are born with abnormally small heads.  As reported in Medical Xpress (January 16, 2020), two teams of researchers at UC San Diego are conducting complementary investigations into how the Zika virus gains access to brain cells.  Both teams have preliminarily concluded that one molecule, avb5 integrin, is singularly essential to the virus’s ability invade brain stem cells.  Integrin molecules, embedded in cell surfaces, are believed to be critical to cell adherence and communication; they are also associated with cancer progression and metastasis.

The first team, led by Tariq Rana, Ph.D, focused on figuring out how the Zika virus gains entry to certain brain cancer cells (glioblastoma).    After isolating 92 different human brain stem genes necessary to Zika infection and replication in a brain cell, researchers determined that the gene for the one that encodes avb5 integrin was uniquely necessary to the process.  Other viruses have multiple points of entry; Zika appears to have just the one. 

The second investigation team, led by Jeremy Rich, M.D., took the identification to the next step: trying to determine if blocking or inhibiting avb5 would prevent Zika infection.  The results were impressive.  Rich’s study found that, by using antibodies or deactivating the gene, they “almost completely blocked the ability of the virus to infect brain cancer stem cells and normal brain stem cells.”

Rana’s team conducted similar testing using two experimental cancer drugs that target avb5 with similarly positive results.   Rana plans a further confirmatory study using an engineered mouse model that lacks the avb5 integrin altogether. 

Building on a study he helped to complete in 2017 which demonstrated the Zika virus’ highly selective preference for glioblastoma stem cells (over healthy brain stem cells) and capitalizing on the virus’ ability to shrink brain tissue, Rich hopes to use the Zika virus to aid in the battle against glioblastoma.  Working with other UC San Diego researchers, including Alysson Muotri, Ph.D. and Pinar Mesci, Ph.D., Rich was able to generate a new brain tumor laboratory model that confirmed that the Zika virus selectively eliminates the brain cancer stem cells.   Rich concludes that “we would likely need to modify the normal Zika virus to make it safer to treat brain tumors, we may also be able to take advantage of the mechanisms the virus uses to destroy cells to improve the way we treat glioblastoma.”  Rich points to the potential surrounding viruses noting that they are “very good at targeting and entering specific cells in the body.” 

~~ David Walsh