Should we be more concerned about bovine leukemia virus?

I was at a meeting in Ottawa when a colleague pointed out to me that there was an exciting new study associating the bovine leukemia virus (BLV) with breast cancer in humans. This is of both veterinary and general interest.

Enzootic bovine leukosis was first recognized in cattle almost 150 years ago but the causative agent, BLV, was not isolated until 1969. Today, BLV is a worldwide concern and, in Canada and the United States, it is considered to cost the dairy industry hundreds of millions of dollars each year. In Canada, 78% of 315 dairy herds from 7 provinces had antibodies to BLV in a 2015 study (1), and it is estimated that 84% of dairy herds in the United States are infected (2). Less than 5% of infected cattle develop clinical disease but subclinically infected animals have the virus in milk, blood, saliva, and nasal secretions. Economic losses are due to reduced production, limitations on exports, deaths, and sequelae to immune dysfunction.

The idea that BLV might infect and cause disease in humans is not new. In the 1970s several studies investigated whether exposure to food products from cattle might result in infection of humans. No antibodies to BLV were detected in human serum samples in these studies and scientists concluded that there was no evidence that BLV was capable of infecting humans. In 2003, however, Gertrude Buehring and coworkers at the School of Public Health, University of California, Berkeley, re-examined the issue, using immunological techniques that were about 100-fold more sensitive than those used in the 1970s (3). They found that 39% of 257 human serum samples tested had antibodies against the BLV p24 capsid antigen. They noted that these findings indicated exposure to BLV antigen and not necessarily infection with BLV. In 2014, these researchers examined 219 human breast tissue samples for the presence of BLV DNA and showed that 44% were positive (4). They also demonstrated that the viral DNA was confined to the secretory mammary epithelial cells and that 6% were positive for BLV p24 capsid protein. These observations are consistent with the notion that the virus may be replicating in some humans.

This brings us to the most recent publication by the same group. In September 2015, Guehring and colleagues reported the results of a case-control study on association of BLV with healthy and cancerous breast tissue (5). They examined 239 archived formalin-fixed paraffin-embedded breast tissue samples for the presence of BLV DNA in mammary epithelial cells. The 239 samples came from 114 women diagnosed with breast cancer, 21 with premalignant changes in breast tissue, and 104 women with neither malignant nor premalignant cells. The researchers determined that BLV DNA was present in 59% of breast tissues from women with breast cancer, from 38% of women with premalignant breast changes, and from 29% of normal control samples. The authors argue that the finding of BLV DNA in almost a third of breast tissues from normal women is not surprising since it may take 20 to 30 years from initiation of carcinogenic events to clinically detectable tumor and that the life cycle of deltaretroviruses is consistent with the findings.

There is no information on how humans become infected with BLV. Transmission from cattle through raw milk and inadequately cooked beef, and from infected humans are considered to be potential routes. The Berkeley researchers point to the need for others to conduct similar studies and for investigations into whether viral infection precedes development of breast cancer.

It is not clear whether this is a good news or a bad news story. If subsequent studies show that BLV does cause breast cancer in humans this will have significant repercussions for the cattle industry. Perhaps attempts should be made to eradicate the infection from cattle now, rather than wait for the final word. On the good side, if BLV is shown to be a cause of some breast cancers, it would likely be possible to screen for infection with BLV and to possibly prevent some breast cancers through elimination of BLV by therapy or vaccination.