Bovine leukemia virus discovered in human blood

Gertrude C Buehring,HuaMin Shen,Michael N Bates,Daniel A Schwartz,Niema Razavian,Anne DeLaney,Zach R Demkovich,David L Chu

doi:10.1186/s12879-019-3891-9

Abstract

BackgroundBovine leukemia virus (BLV) infection is widespread in cattle globally and is present in marketed beef and dairy products. Human infection with BLV has been reported in breast and lung cancer tissues and was significantly associated with breast cancer in 3 case-control studies. The purpose of this current research was to determine if BLV is present in human blood cells and if antibodies to BLV are related to blood cell infection.MethodsStandard liquid PCR and Sanger DNA sequencing were used to test for BLV in buffy coat cells (leukocytes and platelets) of blood specimens from 95 self-selected female subjects.Enzyme-linked immunosorbent assay (ELISA) for IgG, IgM, and IgA was used to detect antibodies to BLV in the plasma of the corresponding blood samples.ResultsBLV DNA was detected in the buffy coat cells of blood in 33/95 (38%) of the subjects by PCR and DNA sequencing. IgG antibodies were detected in 30/95(32%), IgM in 55/95(58%), and IgA in 30/95(32%) of the subjects. There was no significant correlation between presence of the antibodies and presence of BLV DNA.ConclusionsThis first report of BLV in human blood raises the question of whether infection of leukocytes could conceivably lead to leukemia as it does in infected cattle. Also, system wide circulation of infected blood cells could facilitate BLV transit to various internal tissues/organs with potential for their infection and subsequent development of cancer. The most likely route of BLV transmission to humans would be zoonotic, as a foodborne infection. Although eradicated from cattle in some countries, BLV still has a high rate of infection in the Americas, the Middle East, and parts of Europe and Asia. This report of BLV in the blood layer containing human leukocytes/platelets adds important information which could be useful to elucidate possible routes of transmission of BLV to humans and to prevent further human infection.

Highlights

Bovine leukemia virus (BLV) infection is widespread in cattle globally and is present in marketed beef and dairy products
These studies obtained slightly different frequencies of women whose breast tissues were positive for BLV, which would be expected because the proportions of women with breast cancer vs. normal controls were different and the populations were from different countries with distinct variations in ethnicity and dietary preferences: Columbia = 43/105 (41%) [7]; Australia = 59/96 (61%) [10]; Argentina = 12/25(48%) [11]; and two different regions of the USA: East and Southeast = 97/ 218 (44%) [8], and Texas = 73/214 (34%) [9]
Samples positive for the long terminal repeat (LTR) promoter region were sequenced because the LTR is a highly conserved BLV genome region, i.e. not deleted out of the virus genome, and the largest number of subjects were positive for this region

Summary

Introduction

Bovine leukemia virus (BLV) infection is widespread in cattle globally and is present in marketed beef and dairy products. Human infection with BLV has been reported in breast and lung cancer tissues and was significantly associated with breast cancer in 3 case-control studies. Retrotranscribed BLV DNA has been independently identified in the breast tissue (both benign and malignant) of human females in Columbia [7], the USA [8, 9], Australia [10], and Argentina [11] in 5 separate investigations using standard liquid PCR and/ or in situ PCR. This microarray method is estimated to have a sensitivity somewhat less than standard PCR but more than generation sequencing (NGS), which detects only viral DNA integrated into the human genome, often present in concentrations too low (< 1% of the reads) to be detected without amplification [13]

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