UC San Diego Study Points to Virus-Related Acceleration in Some Cancers

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While the human T- cell leukemia virus type 1 (HTLV-1) is known to cause a rare cancer of the immune system’s T-cells called adult T-cell leukemia or ATL in about five percent of those infected, researchers from the San Diego Supercomputer Center (SDSC) and Moores Cancer Center at UC San Diego recently hypothesized that this virus, as well as another lesser-known “cousin” called bovine leukemia virus (BLV), may also play a role in the accelerated development of breast cancer, esophageal cancer, pancreatic cancer, and glioblastoma (brain/spinal cancer).

In a Journal of Cancer Research and Therapy paper published last month called HTLV-1 Can Be Involved in Acceleration of Different Nonhematological Cancers, Valentina Kouznetsova, Steven Chen, and Igor Tsigelny proposed the necessity of studies related to HTLV-1 and BLV affecting other cancers. Kouznetsova is a researcher affiliated with SDSC and on staff at the Moores Cancer Center, while Tsigelny is affiliated with both SDSC and Moores, Chen participated on the research team via the SDSC’s Research Experience for High School Students (REHS) summer internship program.

“One of our interesting findings was that HTLV-1 infected patients in southern Japan without any manifestations of ATL-developed various cancers correlated with the possible HTLV-1 proteins influencing a set of cancer pathways equivalent to cancerogenic mutations,” said Kouznetsova, the lead author of the study.

“This problem is not easy,” added Tsigelny. “To assume that HTLV-1 virus proteins affect different cancers, one of the assumptions would have to be that the virus may spread from T-cells where it usually lives, to other types of cells. It is not obvious how that happens, but a number of anecdotal evidences show that HTLV-1 affects various cancers, not only leukemia. It is possible that other mechanisms also are involved.”

Taking a Closer Look at HTLV-1 and BLV

Because HTLV-1 and BLV encode similar virus proteins, it is important to better understand how these two viruses really work. According to Kouznetsova, while HTLV-1 is contracted in humans via blood and sexual contact, it can also be contracted during breast-feeding as well as from mother to child during pregnancy.

Similarly, BLV is spread from infected cattle to non-infected cattle by direct contact or exposure to blood. While BLV is not believed to survive pasteurization, the virus has the potential to be transmitted from an infected cow’s raw milk to a human. Likewise, the virus may also be able to be transmitted from an infected cow’s undercooked meat to humans. While the cattle industry strives to keep infected cattle segregated from healthy cattle, several studies have found BLV in breast cancer tumors. \

A January 2018 Frontiers in Oncology study showed that 67 (59 percent) of 114 U.S. human breast cancers were positive for BLV when compared with 30 (29 percent) of 104 normal breast controls. An Australian study demonstrated that 40 (80%) of 50 breast cancers were BLV positive when compared with 19 (41 percent) of 46 normal controls. At the same time, one U.S. and one Chinese study demonstrated no BLV in breast cancer tissues.

“This is the problem in development that needs more clinical experiments,” said Tsigelny. “Nevertheless, in the event that the first studies are accurate, it became evident that attempts to eradicate BLV and conduct more studies addressing the cancer pathways activated by HTLV/BLV viruses may be extremely important. It is even more urgent when one takes into account that BLV affects a significant part of U.S. dairy herds.”

According to researchers at Michigan State University (MSU), as of 2018 BLV was prevalent in about 43 percent of all U.S. cattle. However, BLV has been completely eradicated in more than 20 nations, most of which are in Europe, and their efforts can be used as models for implementing several control strategies. Large Animal Clinical Sciences Professor Paul Bartlett at MSU is currently conducting several field trials in which the most infectious cattle are culled or segregated to reduce transmission.

“Other approaches involve controlling biting flies and implementing various management controls to reduce blood-borne transmission,” said Bartlett. “Most of our earlier work involved documenting the specific ways in which BLV disrupts the bovine immune system and discovering the unexpectedly large impact on milk production and dairy cow lifespan.”

While efforts to eradicate BLV in cattle are important by themselves, the research done to date by Kouznetsova, Chen, and Tsigelny have the potential to eventually mitigate multiple cancers’ acceleration caused by those infections.

Tsigelny, along with his work at UC San Diego, is the Chief Science Officer and co-founder of CureMatch, a company which provides decision support for doctors in personalized cancer medicine. “With 4.5 million possibilities to combine around 300 FDA-approved cancer drugs, CureMatch targets multiple cancer mutations at the same time and determines the best combination treatment for each patient,” explained Tsigelny. “While this study is not related to the current tasks of CureMatch, it may become so in the future.”

SDSC Director Michael Norman is a member of the CureMatch Advisory Board. No grant funding was used for this study.