Viral Protein Could Help Fight Infection, Cancer or Autoimmune Diseases

Researchers evaluate how DNA viruses work and how they can be stopped.

The fight against cancer got a little bit easier recently after Florida State University scientists uncovered a viral cellular protein in that inhibits a major DNA sensor and thus the body’s response to viral infection.

The findings suggest that this cellular pathway could be manipulated to help a person fight infection, cancer or autoimmune diseases. The protein is named KicGas.

“We can manipulate the protein and/or the sensor to boost or tune down the immune response in order to fight infectious and autoimmune diseases, as well as cancers,” said Fanxiu Zhu, the FSU Margaret and Mary Pfeiffer Endowed Professor for Cancer Research.

The researchers focused on DNA viruses and how they can cause cancer, a topic that is widely debated by scientists around the world. About 15% of human cancer cases are caused by viruses, so scientists have been seeking answers about how the body responds to viral infection and how some viruses maintain life-long infections.

In recent years, the major DNA sensor in cells, known as cGas, has been identified by scientists. The discovery of this DNA sensor led scientists to further research, as this sensor should have been alerting the body to fight disease brought by a DNA virus.

A DNA virus is an intracellular parasite that contains genetic material. Smallpox, herpes and chickenpox are all examples of diseases caused by DNA viruses. The diseases are very difficult to cure because they take over the cellular machinery of their human host, making it impossible to kill the virus without also harming the body.

While the body is equipped with sophisticated immune systems to cope with infection, many viruses have adapted to these systems, evading and suppressing the body’s immune responses to make infection easy and eradication extremely difficult. The discovery of the new protein is crucial to further exploration of how these DNA viruses work and how they can be stopped.

Zhu’s team of scientists studies Kaposi’s sarcoma-associated herpesvirus (KSHV), a human herpesvirus that causes some forms of lymphoma and Kaposi’s sarcoma, a cancer commonly occurring in AIDS patients and other immunocompromised individuals.

In the study, scientists screened 90 total proteins in a KSHV cell. Findings indicated that one of them directly inhibited the DNA sensor called cGas. Scientists then infected human cell lines with the Kaposi’s sarcoma virus to mimic natural infection. They found that when they eliminated the inhibitor protein, KicGas, the cells produced a stronger immune response.

Zhu has also collaborated with other scientists to better understand how the inhibitor functions.

“Once we figure that out, we can hopefully design something to fight the disease,” Zhu said.

As scientists get closer to understanding the newly found protein, so too do they get closer to being able to manipulate the protein in favor of fighting viral DNA. Only then will researchers be able to truly say they have developed a new route to fighting disease, cancer, and autoimmune disorders.