The prevalence of proviral bovine leukemia virus in peripheral blood mononuclear cells at two subclinical stages of infection

Abstract

The bovine leukemia virus (BLV) is an oncogenic retrovirus that is associated with the development of persistent lymphocytosis (PL) and lymphoma in cattle. While B lymphocytes have been shown to be the primary cellular target of BLV, recent studies suggest that some T lymphocytes and monocytes may be infected by the virus. Because virally altered functions of monocytes and/or T cells could contribute to the development of lymphoproliferative disease, we sought to clarify the distribution of the BLV provirus in subpopulations of peripheral blood mononuclear cells in seropositive cows with and without PL. CD2 ؉ T cells, monocytes, and CD5 ؉ and CD5 ؊ B cells were sorted by flow cytometry and tested for the presence of BLV by single-cell PCR. We did not obtain convincing evidence that peripheral blood monocytes or T lymphocytes contain the BLV provirus in seropositive cows with or without PL. In seropositive cows without PL (n ‫؍‬ 14), BLV-infected CD5 ؉ and CD5 ؊ B cells accounted for 9.2% ؎ 19% and 0.1% ؎ 1.8% of circulating B lymphocytes, respectively. In cows with PL (n ‫؍‬ 5), BLV-infected CD5 ؉ and CD5 ؊ B cells accounted for 66% ؎ 4.8% and 13.9% ؎ 6.6% of circulating B lymphocytes, respectively. The increase in lymphocyte numbers in cows with PL was entirely attributable to the 45-fold and 99-fold expansions of infected CD5 ؉ and CD5 ؊ B-cell populations, respectively. Our results demonstrate that B cells are the only mononuclear cells in peripheral blood that are significantly infected with BLV. On the basis of the absolute numbers of infected cells in seropositive, hematologically normal animals, there appear to be differences in susceptibility to viral spread in vivo that may be under the genetic control of the host.

Cattle Infected with Bovine Leukaemia Virus may not only Develop Persistent B‐cell Lymphocytosis but also Persistent B‐cell Lymphopenia

“…In PL + cattle, 70-80% of the PBL were found to be expanding B cells positive for sIgM and CD5. These results are consistent with earlier reports (Fossum et al, 1988;Depelchin et al, 1989;Matheise et al, 1992;Levkut et al, 1995;Mirsky et al, 1996). Furthermore, our data show that in animals with PL, the number of CD5 ) sIgM + B cells can also increase, but only slightly compared with CD5 + .…”

“…These observations reflect the divergent findings of other authors (Williams et al, 1988;Gatei et al, 1989;Taylor et al, 1992;Sordillo et al, 1994;Stone et al, 1994). The increased number of T cells may imply an activated T-cell-mediated immunity, and is consistent with the findings of Mirsky et al (1996), who observed a tendency towards T lymphocytosis in cattle genetically predisposed to PL. It is assumed that in the pathogenesis of EBL, the genetically controlled immune system is deregulated.…”

“…It is possible that cytotoxic T cells are involved in B-cell elimination in PL ) animals. This is plausible as CD5 + sIgM + B cells represent the major target cells for BLV (Mirsky et al, 1996). However, the reason for the decrease in the number of non-sIgM + B cells is unclear.…”

Comparative organization and function of the major histocompatibility complex of domesticated cattle

“…Over a course of 1 to 3 years, PL develops in 15% to 30% of infected animals. Persistent lymphocytosis is characterized by a chronic increase in the absolute number of provir us-positive CDS' B cells in peripheral blood (66). Tbe development of PL bas been found to be under the control of BoLA in different herds and breeds throughout the world (67)(68)(69)(70)(71)(72).…”

Bovine leukemia virus reduces anti‐viral cytokine activities and NK cytotoxicity by inducing TGF‐β secretion from regulatory T cells

“…Bovine leukemia virus (BLV) is related to the human T-cell leukemia retrovirus type 1 (HTLV-1) and causes enzootic bovine leucosis (EBL) [18,19]. BLV infections are latent in the aleukemic (AL) state, but can emerge as persistent lymphocystosis (PL) with non-malignant polyclonal expansion of CD5 þ B-cells that predominantly harbor BLV provirus, and rarely as malignant B-cell lymphoma in various lymph nodes after long periods of latency [18]. During BLV infection, reduced cellular immune responses play major roles in disease progression and lead to increased susceptibility to other infections [20][21][22].…”