You are out for a stroll during a warm summer evening and a mosquito bites your arm. You immediately recall a recent article in The Blade about Zika virus.

Zika virus, which has recently been detected in the United States, is in the daily news after being suspected in a surge of birth defects in Brazil. But before now most Americans had never heard of the Zika virus because it previously was isolated to Africa and Asia. The first sign of the virus spreading to other regions was seen in 2007 during an outbreak on Yap Island in the Southwestern Pacific Ocean.

Within the last year, Zika virus has traveled to the Americas, with the Centers for Disease Control and Prevention reporting active Zika virus transmission in more than 20 countries and territories.

We now know that the Zika virus is just one member of a group of different flaviviruses causing disease in geographical areas that had previously been disease-free. Other flaviviruses recently discovered in the United States include West Nile virus, Powassan virus, and dengue virus.

Mosquitoes and ticks carry these flaviviruses and can transmit the virus to you when they feed on your blood. The resulting viral infection can range from being undetectable to life-threatening, such as brain inflammation or dangerously high fever and organ failure. Luckily, the percentage of people who become sick after infection is low. For example, only about 1 in 5 individuals infected with Zika virus develops symptoms.

Unfortunately for those who do become ill, there are no specific antiviral treatments available for any flavivirus infection, including Zika virus. The development of such needed therapeutics is a huge challenge. 

In Dr. Travis Taylor’s laboratory at the University of Toledo college of medicine and life sciences, we focus on understanding how flaviviruses and human host cells interact at the molecular level. Specifically, I investigate the interaction between a viral protein called nonstructural protein 3 and a host protein called tumor necrosis factor receptor associated factor 6 or TRAF6. We have selected to study the viral nonstructural protein 3 because it is essential for viral replication, which makes it an ideal antiviral target. 

The human TRAF6 protein works as part of the cellular defense against viruses. Human cells can recognize virus invasion and use TRAF6 to send a message to activate an antiviral response, similar to calling 911 when the burglar alarm goes off in your house. When TRAF6 is not working correctly in a human cell, the cell is more susceptible to virus infection because the message is never sent to turn on antiviral defenses.

Using Langat virus, a model flavivirus, we discovered that nonstructural protein 3 appears to interact directly with TRAF6 during virus infection. Knowing how important TRAF6 is to the human cell antiviral defense, we infected host cells that do not have TRAF6 and measured viral replication.

We expected to see an increase in the amount of virus produced within these defenseless host cells. To our surprise, we found the exact opposite of what we predicted. The production of flavivirus in the TRAF6-deficient host cells was reduced compared to cells that have TRAF6.

To further test this discovery, we treated normal human cells with a drug that inhibits TRAF6. This also caused lower virus replication.

Imagine you are hoping to get help to stop a burglar from breaking in and your 911 call brought police who, instead of helping you, helped the burglar.

We now know from our research that some flaviviruses use the host TRAF6 protein to help themselves multiply, instead of this protein behaving as a host defense molecule as it does for other types of viral infections.

We are currently working to determine exactly how nonstructural protein 3 and TRAF6 interact to help the virus instead of the host cell. We then will focus on how to molecularly disrupt this interaction for therapeutic benefit. Our ultimate goal is to aid in the development of new antiviral treatments against flavivirus infections.

Brian Youseff is an M.D./​Ph.D. student in the infection, immunity, and transplantation track in the department of medical microbiology and immunology in the University of Toledo college of medicine and life sciences biomedical science program. For more information, contact Brian.Youseff@rockets.utoledo.edu or go to utoledo.edu/​med/​grad/​biomedical.

First Published February 1, 2016, 5:00 a.m.