Pathogenicity for humans of human rhinovirus type 2 mutants resistant to or dependent on chalcone Ro 09-0410.
Mutants of human rhinovirus type 2 (HRV-2) resistant to and dependent on the antirhinoviral compound chalcone Ro 09-0410 were selected in cell culture under clean laboratory conditions. A total of 42 volunteers were challenged with either the drug-resistant mutant [SR2-410(r)] (15 volunteers), the drug-dependent mutant [SR2-410(d)] (15 volunteers), or a wild-type HRV-2 which had a similar passage level in vitro as the mutants but without the drug (12 volunteers). Of volunteers challenged with the wild-type HRV-2, 33, 67, and 82% developed cold symptoms, shed virus, and showed serological evidence of infection, respectively. In contrast, only 13, 27, and 23% of volunteers challenged with the drug-resistant mutant developed colds, shed virus, and showed serological evidence of infection, respectively. None of the volunteers challenged with the drug-dependent virus became infected or had symptoms of colds. These results demonstrate that a drug-resistant rhinovirus was capable of infecting humans and producing disease, although its infectivity was reduced when compared with that of the wild type. In contrast, a drug-dependent virus had lost its ability to infect humans.
Yasin
S R
SR
Medical Research Council Common Cold Unit, Harvard Hospital, Salisbury, Wiltshire, United Kingdom.
al-Nakib
W
W
Tyrrell
D A
DA
D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology*; D002599:Chalcone / Q000031:analogs & derivatives / Q000494:pharmacology*; D047188:Chalcones; D004352:Drug Resistance, Microbial / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009154:Mutation; D009500:Neutralization Tests; D011427:Propiophenones / Q000494:pharmacology*; D011897:Random Allocation; D012229:Rhinovirus / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity*
D000998:Antiviral Agents; D047188:Chalcones; D011427:Propiophenones; D002599:Chalcone; C036425:Ro 09-0410