Sendai Viruses with Altered P, V, and W Protein Expression

Abstract

Wild-type Sendai virus expresses three proteins containing the N-terminal half of the P protein open reading frame due to mRNA editing; a full-length P protein (ca. 70% of the total), a V protein with the N-terminal half fused to a Cys-rich Zn2+-binding domain (ca. 25% of the total), and a W protein representing the N-terminal half alone (ca. 5% of the total). To examine the role of these proteins in the virus life cycle, we have prepared recombinant viruses in which the normal V mRNA expresses a W protein (V-stop; 70% P, 30% W), one which cannot edit its P gene mRNA (Δ6A; 100% P), and one which overedits its mRNA like parainfluenza virus type 3 (swap/8; 20–40% P, 30% V, 30% W). All these viruses were readily recovered and grew to similar titers in eggs, and except for the P gene products, cell lines individually infected with these viruses accumulated similar amounts of viral macromolecules. The relative competitive advantage of each virus was determined by multiple cycle coinfections of eggs and found to be rSeV-Vstop= rSeV-wt ⪢ rSeV-Δ6A > rSeV-swap/8. On the other hand, rSeV-swap/8 underwent multiple cycles of replication in C57Bl/6 mouse lungs and was highly virulent for these animals, whereas rSeV-Δ6A was avirulent in mice and this infection was quickly cleared. Remarkably, rSeV-Vstopappeared to be more virulent for inbred C57Bl/6 mice than rSeV-wt, but was partially attenuated in infections of outbred ICR mice. Thus, the expression of either the V or the W proteins is sufficient for multiple cycles of infection and pathogenesis in C57Bl/6 mice, whereas W can only partially substitute for V for pathogenesis in ICR mice.