Evidence for bovine leukemia virus in mammary epithelial cells of infected cows

Abstract

Background: Bovine leukemia virus (BLV), a retrovirus, usually causes a subclinical infection of dairy and beef cattle, but in < 1% of infected cattle a B cell lymphoma may develop after several years of infection. BLV is transmitted horizontally among cattle, and infected animals have anti-BLV titers. Expression of BLV antigen, however, is silent in peripheral blood lymphocytes in vivo. The tropism of BLV has been assumed to be limited to B lymphocytes, because no other cell type has been found to harbor the virus in vivo. Since retrovirus-like particles had been identified in milk, and infection can be transmitted by milk, we decided to investigate whether BLV was in mammary epithelial cells.

Experimental design: Pure cultures of mammary epithelial cells were established from cells shed into the milk of 28 cows. BLV was searched in these cultures by immunocytochemistry and the polymerase chain reaction, the specificity of the latter confirmed by Southern blot hybridization and DNA sequencing. BLV was searched immunocytochemically in mammary tissue sections from 12 cows.

Results: Antigenic and/or molecular evidence of BLV was found in the cultured cells of 20 cows. Antigenic evidence of BLV was found in tissue sections from 10 cows, indicating virus expression in vivo. Simultaneous detection of BLV p24 and cytokeratins, localized antigen expression to the mammary epithelial cells.

Conclusions: These indications of BLV in mammary epithelial cells in vivo suggest that BLV is capable of infecting and expressing antigen in glandular epithelium in vivo and has a broader tissue tropism than was previously thought. They raise the question of how persistent mammary infection by BLV may influence the course of bovine lymphoma, and what effect the virus may have on the mammary gland.