Medicine News

Ebola as MEDICINE? Protein expressed by Ebola virus enables selective targeting and elimination of brain tumors

The Ebola virus (EBOV) is notorious for causing outbreaks and a deadly disease known as a viral hemorrhagic fever. An aggressive pathogen by nature, EBOV not only infects different organs and cells, it also produces several proteins that help it evade the human body’s immune response to viruses.

But researchers recently discovered a way to manipulate and put one of these proteins to good use. Using recombinant technology, a team from Yale University School of Medicine and Albany Medical College created an artificial virus that expresses this protein and showed that it can selectively target and eliminate brain tumors in mice without causing a brain infection.

Why use a virus?

One of the things viruses are known for is their selectivity. As in the case of polioviruses, which target and destroy motor neurons, most viruses have an affinity for a specific type of cell or tissue. In fact, there are viruses that show a tendency to infect and kill cancer cells exclusively. Called oncolytic viruses, this group includes viruses that can be found in nature, as well as viruses that have been modified by scientists to enhance their targeting efficiency. To date, only one genetically modified oncolytic virus has been approved by the US Food and Drug Administration, and it is used for the treatment of melanomas. (Related: Flu viral strain found to actually CURE liver cancer in groundbreaking research that obliterates medical narratives of the status quo.)

Another reason why scientists find viruses attractive tools for cancer therapy is that most cancer cells lack the ability to defend themselves against viruses. This strategy, however, carries an inherent risk: As the team led by Yale researchers discovered in their previous study, an artificially created (chimeric) virus can remain active in the brain after destroying tumor cells. It can then cause widespread infection of normal brain cells and jeopardize the survival of patients despite eliminating the brain tumor.

Scientists take advantage of EBOV’s inability to infect nerve cells

For their study, the researchers used a modified version of the vesicular stomatitis virus (VSV). Normal VSV selectively targets cells of the central nervous system. The team replaced the gene responsible for VSV’s toxic effect on nerve cells with a gene from EBOV. Despite its reputation as a deadly and aggressive pathogen, EBOV is not neurotropic, meaning it does not attack the nervous system. By using a chimeric VSV that expresses the Ebola protein, the team mitigated the risk of a brain infection while ensuring the selective targeting of brain tumor cells.

The Ebola gene they inserted into the chimeric VSV encodes a glycoprotein with a mucin-like domain (MLD). The researchers believe that this MLD is part of the reason why EBOV can evade immune system detection. They hope that it would give their chimeric VSV the same ability so it could work more efficiently against brain cancer cells.

Using mice with gliomas — a dangerous type of brain tumor — the researchers compared the effects of a chimeric VSV expressing MLD and a chimeric VSV that expresses the Ebola glycoprotein but without MLD. They found that the latter replicated itself at a much faster rate than the chimeric VSV with MLD. On the other hand, while the VSV with no MLD targeted gliomas, it did not prolong the survival of mice with gliomas.

In contrast, the VSV expressing the full Ebola protein including MLD showed substantially better targeting and elimination of brain tumors. It also increased the survival of the brain tumor-bearing mice. While the VSV without MLD began infecting normal brain cells after eliminating tumors, the VSV with MLD caused relatively little infection, suggesting that the Ebola glycoprotein’s MLD protected normal brain cells from viral infection. When tested in mice without gliomas, neither of the two VSVs showed substantive infection in the brain.

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