Seroconversion of sheep experimentally infected with enzootic nasal tumor virus

Abstract

Background: Enzootic nasal tumor virus (ENTV-1) is an exogenous betaretrovirus of sheep that transforms epithelial cells lining the ethmoid turbinates leading to a disease called enzootic nasal adenocarcinoma (ENA). A unique feature of ENA is the apparent absence of a specific humoral immune response to the virus, despite the highly productive infection in nasal tumors. The sheep genome contains approximately 27 copies of endogenous ovine betaretroviral sequences (enJSRVs) and expression of enJSRVs in the ovine placenta and uterine endometrium throughout gestation is thought to induce immunological tolerance to exogenous ovine betaretroviruses, a factor that may influence the likelihood of exogenous ENTV infection and disease outcome. Nevertheless, we recently demonstrated the presence of neutralizing antibodies directed against the ENTV-1 envelope glycoprotein in sheep naturally exposed to ENTV-1.

Findings: Here, we employed an ENTV-1 envelope glycoprotein surface subunit specific ELISA and a virus neutralization assay to monitor serum antibody responses to ENTV-1 in a group of lambs experimentally infected with ENTV-1 virus containing filtered ENA tumor homogenate. Seroconversion and development of neutralizing antibodies was detected in one of six experimentally infected lambs.

Conclusions: Our results demonstrate that sheep can respond immunologically and seroconvert following ENTV-1 infection suggesting that anti-viral immune responses may play a role in the development of ENA.

Fig. 1

ELISA detection of serum antibodies reactive against the ENTV-1 envelope protein and causing neutralization of an ENTV-1 envelope protein pseudotyped retroviral vector. Sheep serum samples were evaluated in an indirect ELISA using purified ENTV-1 envelope (ESU-IgG) protein as the target antigen. The dashed line represents the background cut off value generated using serum from SPF sheep. The solid line with circular points represents results from the sheep that seroconverted following ENTV-1 infection and the dotted line with square points is representative of a non-seroconverter. ENTV-1 envelope pseudotyped MLV particles carrying the human placental alkaline phosphatase reporter gene were incubated with the indicated serum samples prior to infection of NIH 3T3/LL2SN cells [11]. The percent reduction in hPLAP positive foci is graphed