Augmentation of Bovine Leukemia Virus (BLV)‐Specific Lymphocyte Proliferation Responses in Ruminants by Inoculation with BLVenv‐Recombinant Vaccinia Virus: Their Role in the Suppression of BLV Replication

Abstract

Lymphocyte proliferation responses were investigated in sheep and cattle, in which the replication of bovine leukemia virus (BLV) had been known to be suppressed by inoculation with recombinant vaccinia virus (rVV) expressing BLV envelope glycoprotein (gp60). Enhanced lymphocyte proliferation responses were observed in animals inoculated with rVV, regardless of whether they were naive or BLV carriers. These responses were roughly inversely correlated to the growth of BLV in the peripheral blood leukocytes. In contrast, there was no apparent correlation between humoral immune response and BLV growth. Based on these results, it was suggested that rVV rendered its suppressive effect of BLV replication primarily via augmentation of cell-mediated immunity.Bovine leukemia virus (BLV) is a type C retrovirus which causes a malignancy of B-cell lineage termed enzootic bovine leukosis in cattle, and shares biological and pathological properties with human T-lymphotropic leukemia virus types I and II (HTLV-I, -II) (1, 5, 10). Determination of the complete nucleotide sequences of these viruses (16)(17)(18)(19) revealed that the organization of their genes is similar. BLV infection usually occurs horizontally and is characterized by a long latent period. It also induces leukemia in sheep at a high incidence within a relatively short period (7, 13), making sheep a good animal model for research on BLV.An increasing amount of data show that the induction of strong humoral immune response to BLV envelope glycoprotein was able to completely protect naive sheep against BLV infection (8,14). Our knowledge is sparse, however, of the immunological mechanisms controlling the replication of BLV after its infection of an animal. To investigate this, we conducted a series of experiments in sheep 131 7

Host Immune Responses in the Course of Bovine Leukemia Virus Infection.

“…Thus, production of PGE 2 and the change of macrophage functions contribute to the suppression of CMI responses in the disease-progressed animals. Ohishi et al also supported the critical roles of CMI to eliminate BLV infected cells [41,42,59]. Recombinant vaccinia virus encoding BLVenv gene (rVVenv) was constructed and injected into sheep.…”

“…Both humoral and cell-mediated immunity (CMI) are known to be induced in natural BLV-infection, and these play roles in protection of hosts from BLV infection [20,29,41,42,45]. However, their relative roles in protection remain to be elucidated.…”

“…However, their relative roles in protection remain to be elucidated. In this regard, a series of recent studies have postulated that particularly CMI against BLV antigens contributes to the suppression of BLV replication, this leading to the delay of disease progression [42,59]. Orlik and Splitter have shown that CMI responses to BLV antigens were suppressed in correlation to disease progression [46].…”

“…Sheep which were immunized with rVVenv and protected from the infection showed no antibody responses but good DTH response, which is supposed to be mediated by helper T cell type 1 (Th1) [7]. In addition, statistical analysis demonstrated the relationship among BLV titers in peripheral blood mononuclear cell (PBMC) and lymphocyte proliferative responses against BLV antigens [42].…”

“…Sheep which were immunized with rVVenv and protected from the infection showed no antibody responses but good DTH response, which is supposed to be mediated by helper T cell type 1 (Th1) [7]. In addition, statistical analysis demonstrated the relationship among BLV titers in peripheral blood mononuclear cell (PBMC) and lymphocyte proliferative responses against BLV antigens [42].In order to prevent BLV infection or disease progression, a vaccine should be able to induce BLV-specific CMI responses. Recently, it has been reported that inactivated protein antigens with adjuvants can induce CMI including the activation of cytotoxic T lymphocyte (CTL) response [33,51,56,61].…”