TOPOGRAPHY OF VARIOLA SMALLPOX VIRUS INVERTED TERMINAL REPEATS

We examined the nucleotide sequences of the inverted terminal repeat ( ITR) regions adjacent to the covalently closed hairpin end sequences o f three variola major and four minor strains from smallpox outbreaks i n Europe, Asia, Africa, and South America. The ITR regions ranged in s ize from 581 to 1051 base pairs (bp) and contained no apparent open re ading frames. Two nonrepetitive sequence elements, NR1 and NR2, were c onserved and resembled nonrepetitive elements in the ITRs of other ort hopoxviruses. Depending on strain, the terminally positioned NR1 and t he more internal NR2 flanked a direct repeat region containing from no ne to four copies of a 69-bp sequence and one copy of a 54-bp related sequence partial repeat. A distinctive pattern of ITR topography of NR 1 and NR2 flanking a single copy of the 69-bp unit characterized each of three examined alastrim variola minor strains. A nonalastrim Africa n minor strain from the last natural case of smallpox in somalia in 19 77 showed the largest ITR region of the examined viruses because of a second direct repeat cluster following NR2. (C) 1995 Academic Press, I nc.