Interference with viral infection by transgenesis or tissue specific expression.

Two strategies to target molecules interfering with virus replication into mucosal areas have been developed. One strategy is based on the development of expression vectors based on RNA minigenomes or full-length infectious cDNAs derived from coronavirus (TGEV), and the other one, the development of transgenic animals providing virus neutralizing antibodies in the milk during lactation. The helper dependent expression system produced significant amounts of the heterologous antigens (1 to 8 mug/10(6) cells). These expression levels were considerably increased with the single genome vectors (> 20 mug/10(6) cells). The possibility of engineering the tissue and species tropism will make the coronavirus very flexible expression systems, since the same vector could be modified to target expression to different organs and animal species, including humans. Transgenic mice expressing in the milk high levels of TGEV neutralizing rIgG and rIgA under WAP and beta -lactoglobulin promoters, respectively, have been obtained. These animals produce virus neutralizing antibodies in the milk that reduce virus infectivity more than one million-fold. Since mAbs specific for many viruses infecting the enteric tract are available, this strategy could be a general procedure to generate animals resistant to viral infections of the enteric tract.