Monkeypox virus (MPV) causes a human disease which resembles smallpox but w
ith a lower person-to-person transmission rate. To determine the genetic re
lationship between the orthopoxviruses causing these two diseases, we seque
nced the 197-kb genome of MPV isolated from a patient during a large human
monkeypox outbreak in Zaire in 1996. The nucleotide sequence within the cen
tral region of the MPV genome, which encodes essential enzymes and structur
al proteins, was 96.3% identical with that of variola (smallpox) virus (VAR
). In contrast, there were considerable differences between MPV and VAR in
the regions encoding virulence and host-range factors near the ends of the
genome. Our data indicate that MPV is not the direct ancestor of VAR and is
unlikely to naturally acquire all properties of VAR. (C) 2001 Published by
Elsevier Science B.V. on behalf of the Federation of European Biochemical
Societies.