Map of the RSV genome and spectrum of attenuation exhibited by gene-deletion viruses. (a) Map of the RSV genome, a single negative-sense RNA of 15.2 kb. Each viral gene is represented by a box, and the gene-start and gene-end transcription signals that flank each gene are indicated by gray and black bars, respectively. The 3′ and 5′ ends of the genome consist of the extragenic leader (Le) and trailer (Tr) regions, respectively. The genes are separated by short intergenic regions except in the case of the M2 and L genes, which overlap but are nonetheless transcribed into separate mRNAs, as are all of the other genes (1). The diagram is only approximately to scale. (b) Mean peak virus titers in the upper (nasopharynx) and lower (tracheal lavage) respiratory tract of chimpanzees that had been inoculated by the intranasal and intratracheal routes simultaneously with the indicated gene-deletion virus or, as controls, with wild-type RSV or with the rRSVcpts248/404 virus. This last virus serves as a reference point for a virus with mild residual virulence for seronegative infants (4).