Lk. Crawfordmiksza et Dp. Schnurr, ADENOVIRUS SEROTYPE EVOLUTION IS DRIVEN BY ILLEGITIMATE RECOMBINATIONIN THE HYPERVARIABLE REGIONS OF THE HEXON PROTEIN, Virology, 224(2), 1996, pp. 357-367
The origin of AIDS-associated adenoviruses (AV 43-AV 49) was investiga
ted by examining evolutionary relationships among 18 serologically rel
ated subgenus D serotypes and 3 intermediates and determining the muta
tion rate of a single serotype, AV 48, among clinical isolates from AI
DS patients over a 6-year period. Nucleotide sequence of conserved and
seven hypervariable regions (HVRs) of the hexon protein, the pVI core
protein signal peptide, and noncoding region between the two genes wa
s determined. Among AV 48 isolates the base misincorporation rate was
3.2 per 10,000 bases over 6 years. A 6-bp deletion occurred in one iso
late between short direct repeats in HVR 7, Among subgenus D serotypes
mutation rates were extremely low in the pVI peptide, the 5' hexon no
ncoding region, and first 187 bases of hexon protein. Small 2-and 3-bp
deletions between short direct repeats in a polypurine stretch in the
noncoding region occurred in 3 strains, Mutation increased with proxi
mity to the HVRs. Within HVR 1, 2, 4, 5, and 7 variability consisted o
f extensive intrachromosomal illegitimate recombination, including del
etions between short direct repeats, insertions and duplications in re
petitive polypurine stretches, and numerous base substitutions. All se
rotypes and intermediates differed by at least one illegitimate recomb
ination event, with one exception. We conclude that AV serotype evolut
ion is driven by illegitimate recombination events (antigenic shift),
concommitant with single base mutation (antigenic drift), and that the
HVRs are ''hot spots'' for both. These events could be explained by s
lippage-misalignment of the AV DNA polymerase in repetitive polypurine
stretches during single-strand DNA replication. This mutability in th
e suriace regions of the major viral coat protein confers a distinctsu
rvival advantage to this family of viruses. (C) 1996 Academic Press, I
nc.