Allele-specific adaptation of poliovirus VP1 B-C loop variants to mutant cell receptors

作者：Liao S; Racaniello V

来源：Journal of Virology, 1997, 71(12): 9770-9777.

Previous work has shown that three different mutations in domain 1 of the poliovirus receptor (Pvr), two in the predicted C'-C '' ridge and one in the D-E loop, abolish binding of the P1/Mahoney strain. All three receptor defects could be suppressed by a mutation in the VP1 B-C loop of the viral capsid that was present in all 16 P1/Mahoney isolates adapted to the mutant receptors. To identify allele-specific mutations that enable poliovirus to utilize mutant receptors, and to understand the role of the VP1 B-C loop in adaptation, we selected mutant receptor-adapted viruses derived from two P1/Mahoney variants, one which lacks the VP1 B-C loop and one in which the VP1 B-C loop is replaced with the corresponding sequence from the P2/Lansing strain. Six adapted viral isolates were obtained after passage on mutant receptor-expressing cell lines. Sequence analysis revealed that each virus contained three to five mutations, and a total of 18 amino acid changes at 17 capsid residues were identified. Site-directed mutagenesis was used to evaluate the role of these mutations in adaptation to mutant Pvr. The results demonstrate that mutations in the viral canyon floor and rim are allele specific and compensate only for receptor defects in the C'-C '' ridge of Pvr, suggesting that these sites interact in the virus-receptor complex. Furthermore, mutations in the VP1 E-F loop suppressed Pvr D-E loop defects, implying that the Pvr D-E loop contacts the VP1 E-F loop. Most of the other mutations mapped to interior capsid residues, some interacting with the fivefold- or threefold related protomers. These mutations may regulate receptor interaction by controlling the structural flexibility of the viral capsid. In viruses lacking the VP1 B-C loop, single mutations were not sufficient to confer the adapted phenotype, in contrast to the 414 virus, which contains the B-C loop. Although the VP1 B-C loop appeared to be dispensable for adaptation, it may have provided a selective advantage in adaptation of P1/Mahoney to mutant Pvr.

• 出版日期1997-12