Retroviruses, HIV, Epstein Barr Virus and B cell lymphoma, $6 million, five-year grant from the National Cancer Institute

Researchers: Douglas Nixon (contact PI);  Cedric Feschotte; Ethel Cesarman, professor of pathology and laboratory medicine and an expert on herpes viruses at Weill Cornell Medicine; and Fabio Leal, a researcher at the Brazilian National Cancer Institute, who will provide samples from lymphoma patients, with and without HIV.     

People living with HIV have higher incidences of B cell lymphomas compared with the general population. Similarly, there is evidence that Epstein Barr Virus also promotes these lymphomas.

Endogenous retroviruses, which make up around 8% of the human genome, may answer this riddle. Researchers believe these viruses infected germ (egg and sperm) cells millions of years ago, were passed from mother to child, and over time their genetic sequences became incorporated in the human genome. Research shows that retroviral sequences may be involved in the development of cancers.

The team will explore how HIV and Epstein Barr Virus interact with retroviral sequences inside our genome. They will test whether HIV infections ­may activate ancient viral elements, creating feedback loops that promote inflammation that indirectly lead to lymphoma.

Also, HIV infections may activate genes that originate in retroviral elements, prompting them to express signaling proteins, which create cross-talk between cells and may disrupt regulation of B cells and promote B-cell lymphoma. The work may provide a new source of antigenic targets for immune T-cells or antibodies that could lead to lymphoma therapies.

A $75,000 Academic Integration Multi Investigator Seed Grant in 2019 to Nixon and Feschotte led to preliminary data, but perhaps more importantly created a purpose and funds for the researchers and their teams members to travel between Ithaca and New York City during the pandemic.

“Without the seed grant, we probably wouldn’t have gotten this [National Cancer Institute] grant,” Nixon said. “The person-to-person meetings and getting the younger people in our labs lab to know each other and start to collaborate has set up a long-term future of more collaborative programs.”

The seed grant began as a different study related to retroviruses and HIV latency in cells, which contributed to a separate collaboration and a recent multi-institution National Institutes of Health award for $26.5 million, including $5.7 million for Cornell. The project will be led by researchers at Gladstone Institutes, Scripps Research and Weill Cornell Medicine. Lishomwa Ndhlovu, professor of immunology in medicine at Weill Cornell Medicine is a PI, and Nixon and Feschotte are both co-investigators.