THE COMPLETE GENOMIC SEQUENCE OF THE MODIFIED VACCINIA ANKARA STRAIN - COMPARISON WITH OTHER ORTHOPOXVIRUSES

The complete genomic DNA sequence of the highly attenuated vaccinia st rain modified vaccinia Ankara (MVA) was determined. The genome of MVA is 178 kb in length, significantly smaller than that of the vaccinia C openhagen genome, which is 192 kb. The 193 open reading frames (ORFs) mapped in the MVA genome probably correspond to 177 genes, 25 of which are split and/or have suffered mutations resulting in truncated prote ins. The left terminal genomic region of MVA contains four large delet ions and one large insertion relative to the Copenhagen strain. In add ition, many ORFs in this region are fragmented, leaving only eight gen es structurally intact and therefore presumably functional. The insert ed DNA codes for a cluster of genes that is also found in the vaccinia WR strain and in cowpox virus and includes a highly fragmented gene h omologous to the cowpox virus host range gene, providing further evide nce that a cowpox-like virus was the ancestor of vaccinia. Surprisingl y, the central conserved region of the genome also contains some fragm ented genes, including ORF F5L, encoding a major membrane protein, and ORFs F11L and O1L, encoding proteins of 39.7 and 77.6 kDa, respective ly. The right terminal genomic region carries three large deletions: a ll classical poxviral immune evasion genes and all ankyrin-like genes located in this region are fragmented except for those encoding the in terleukin-1 beta receptor and the 68-kDa ankyrin-like protein B18R. Th us, the attenuated phenotype of MVA is the result of numerous mutation s, particularly affecting the host interactive proteins, including the ankyrin-like genes, but also involving some structural proteins. (C) 1998 Academic Press.