Nature 366, 748 - 751 (30 December 1993); doi:10.1038/366748a0

Potential virulence determinants in terminal regions of variola smallpox virus genome

Robert F. Massung^*, Joseph J. Esposito^*†, Li-ing Liu^‡§, Jin Qi^*, Theresa R. Utterback^‡§, Janice C. Knight^*, Lisa Aubin^‡§, Thomas E. Yuran^*, Joseph M. Parsons^*, Vladimir N. Loparev^*, Nickolay A. Selivanov^‡, Kathleen F. Cavallaro^*, Anthony R. Kerlavage^‡§, Brian W. J. Mahy^* & J. Craig Venter^‡§

^*Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA
^‡National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA
^§The Institute for Genomic Research, Gaithersburg, Maryland 20878, USA
^†To whom correspondence should be addressed.

SMALLPOX eradication culminated the most successful antimicrobial campaign in medical history¹. To characterize further the linear double-stranded DNA genome of the aetiological agent of smallpox, we have determined the entire nucleotide sequence of the highly virulent variola major virus, strain Bangladesh-1975 (VAR-BSH; 186,102 base pairs, 33.7% G + C; Genbank accession number, L22579). Here we highlight features of the molecule and focus on a few of the 187 putative proteins that probably contribute to pathogenicity and virus host-range properties. One hundred and fifty proteins were markedly similar to those of vaccinia virus (smallpox vaccine), for which a complete sequence has been reported^2,3 for strain Copenhagen (VAC-CPN; 191,636 base pairs, 33.3% G + C). The remaining 37 proteins reflected variola-specific sequences or open reading frame divergences for variant proteins, which are often truncated or elongated compared with their vaccinia counterparts.

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