Caprine arthritis-encephalitis virus: Intestinal transmission and neutralizing antibody responses

Caprine arthritis-encephalitis virus (CAEV) is a lentivirus genetically related to HIV, SIV, EIAV and maedi/visna. Transmission occurs most efficiently by ingestion of milk or colostrum containing CAEV. Entry of CAEV into the systemic circulation may therefore occur after crossing the gastrointestinal mucosa. Following infection with CAEV, goats develop variable neutralizing antibody responses which are typically low titer and have limited strain cross reactivity. Current data indicate that neutralizing antibody may be important in protection against lentiviral infection acquired by intravascular inoculation or across the gastrointestinal and urogenital mucosae. The goals of this project were to (1) delineate a route of CAEV transmission across the intestinal mucosa, (2) generate neutralizing antibody responses in CAEV SU vaccinated goats which may be used to block CAEV intestinal transmission and (3) investigate mechanism(s) which may explain the variability of neutralizing antibody responses in CAEV infected goats.; Intestinal transmission of CAEV was demonstrated by inoculating CAEV into a surgically isolated intestinal segment and finding CAEV infected intestinal epithelial and mononuclear cells of the mucosa and mononuclear cells of the submucosa using an in situ hybridization assay. Entry of CAEV into the systemic circulation was confirmed by detection of CAEV specific antibodies in serum and by detection of CAEV DNA in inoculated goat PBMC by PCR analysis.; Variable homologous and heterologous neutralizing antibody responses were detected in goats vaccinated with purified CAEV SU. Also, infection-enhancing antibody was detected and shown to compete with neutralizing antibodies.; These results suggested that CAEV crosses the intestinal mucosa by infecting cells at all levels of the intestinal mucosa and submucosa. Also, vaccination of goats with CAEV SU induced both homologous and heterologous neutralizing antibody. In addition to neutralizing antibody, SU vaccination induced infection-enhancing antibodies. The observed variability in neutralizing antibody responses in CAEV infected goats therefore may be due to competition between infection-enhancing and neutralizing antibodies.