Scientists pinpoint protein that helps cancer-causing viruses evade immune response

The viruses Kaposi sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) have been linked to several cancers. For the first time, UNC School of Medicine scientists have discovered that these viruses use a human protein called barrier-to-autointegration factor 1, or BAF, to evade our innate immune response, allowing the viruses to spread and cause disease.

These findings, published in Nature Communications, suggest that BAF and related proteins could be therapeutic targets to prevent these viruses from spreading and leading to cancers, such as Kaposi sarcoma, non-Hodgkin lymphoma, Hodgkin lymphoma, multicentric Castleman disease, nasopharyngeal carcinoma, and gastric cancer.

"Viruses are in a constant battle with the cellular immune system, which includes the protein cyclic GMP-AMP synthase, or cGAS, which binds to viral DNA and sounds the alarm to trigger immune responses and fight the viral invaders," said senior author Blossom Damania, PhD, the Boshamer Distinguished Professor of Microbiology and Immunology and member of the Lineberger Comprehensive Cancer Center. "We've discovered that KSHV and EBV use a different host cell protein, BAF, to prevent cGAS from sounding the alarm."

Viruses have evolved with humans for millions of years, so it's no surprise they've evolved tricks to evade our natural, or innate, immune responses. Finding out precisely how viruses do this is the basis for creating vaccines and therapeutics to overcome their tricks.

In the case of KSHV and EBV, the expression of BAF is increased upon infection, suggesting that these viruses take advantage of this host protein to blunt the immune response to infection. In a series of experiments, Damania’s lab found that BAF contributes to the degradation of the cGAS DNA sensor. With less cGAS protein available in the infected cell to detect DNA, the cells mount weaker immune responses, which allows these two viruses to replicate and spread more efficiently.

"BAF enables EBV and KSHV to reactivate from latency, replicate, and make more of themselves," said first author Grant Broussard, a graduate student in the Genetics and Molecular Biology Curriculum at UNC Lineberger. "Our study highlights the prominent role that DNA detection pathways like the cGAS pathway play in controlling viral infection."

He stressed that disrupting BAF activity with targeted therapies could reduce its immunosuppressive effects, thus restricting replication of these viruses to prevent the spread of disease.

Damania, who is a Leukemia and Lymphoma Society Scholar and a Burroughs Wellcome Fund Investigator in Infectious Diseases, added, "Preventing lytic replication will prevent transmission of these viruses and also reduce the global cancer burden associated with these two viruses."

Broussard, G., Ni, G., Zhang, Z. et al.
Barrier-to-autointegration factor 1 promotes gammaherpesvirus reactivation from latency.
Nat Commun 14, 434, 2023. doi: 10.1038/s41467-023-35898-2

Most Popular Now

Engineered bacteria find tumors, then alert the au…

Combining discoveries in cancer immunology with sophisticated genetic engineering, Columbia University researchers have created a sort of "bacterial suicide squad" that ...

Scientists reveal a potential new approach to trea…

Scientists at the National Institutes of Health and Massachusetts General Hospital in Boston have uncovered a potential new approach against liver cancer that could lead ...

Pfizer invests $43 billion to battle cancer

Pfizer Inc. (NYSE: PFE) and Seagen Inc. (Nasdaq: SGEN) today announced that they have entered into a definitive merger agreement under which Pfizer will acquire Seagen, a...

First nasal monoclonal antibody treatment for COVI…

A pilot trial by investigators from Brigham and Women's Hospital, a founding member of the Mass General Brigham healthcare system, tested the nasal administration of the ...

AstraZeneca launches call for entries to the 2023 …

AstraZeneca has announced the launch of the 2023 R&D Postdoctoral Challenge, an initiative designed to accelerate ideas to transform the treatment of some of the world’s ...

US FDA Advisory Committee votes to support effecti…

GSK plc (LSE/NYSE: GSK) announced that the US Food and Drug Administration (FDA) Vaccines and Related Biological Products Advisory Committee (VRBPAC) voted that the avail...

Tumour cells' response to chemotherapy is driven b…

Cancer cells have an innate randomness in their ability to respond to chemotherapy, which is another tool in their arsenal of resisting treatment, new research led by the...

Pfizer's ZAVZPRET™ (zavegepant) migraine nasal spr…

Pfizer Inc. (NYSE: PFE) today announced the U.S. Food and Drug Administration (FDA) has approved ZAVZPRET™ (zavegepant), the first and only calcitonin gene-related peptid...

Normalizing tumor blood vessels may improve immuno…

A type of immune therapy called chimeric antigen receptor (CAR)-T cell therapy has revolutionized the treatment of multiple types of blood cancers but has shown limited e...

Gene and cell therapies to combat pancreatic cance…

Pancreatic cancer is an incurable form of cancer, and gene therapies are currently in clinical testing to treat this deadly disease. A comprehensive review of the gene an...

DNA treatment could delay paralysis that strikes n…

In virtually all persons with amyotrophic lateral sclerosis (ALS) and in up to half of all cases of Alzheimer's disease (AD) and frontotemporal dementia, a protein called...

Novartis Tafinlar + Mekinist approved by FDA for p…

Novartis today announced the U.S. Food and Drug Administration (FDA) granted approval for Tafinlar® (dabrafenib) + Mekinist® (trametinib) for the treatment of pediatric p...