Sequence and structure of human rhinoviruses reveal the basis of receptor discrimination.
The sequences of the capsid protein VP1 of all minor receptor group human rhinoviruses were determined. A phylogenetic analysis revealed that minor group HRVs were not more related to each other than to the nine major group HRVs whose sequences are known. Examination of the surface exposed amino acid residues of HRV1A and HRV2, whose X-ray structures are available, and that of three-dimensional models computed for the remaining eight minor group HRVs indicated a pattern of positively charged residues within the region, which, in HRV2, was shown to be the binding site of the very-low-density lipoprotein (VLDL) receptor. A lysine in the HI loop of VP1 (K224 in HRV2) is strictly conserved within the minor group. It lies in the middle of the footprint of a single repeat of the VLDL receptor on HRV2. Major group virus serotypes exhibit mostly negative charges at the corresponding positions and do not bind the negatively charged VLDL receptor, presumably because of charge repulsion.
Vlasak
Marketa
M
Institute of Medical Biochemistry, University of Vienna, Vienna Biocenter (VBC), A-1030 Vienna, Austria.
Blomqvist
Soile
S
Hovi
Tapani
T
Hewat
Elizabeth
E
Blaas
Dieter
D
D000595:Amino Acid Sequence; D001665:Binding Sites; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011973:Receptors, LDL / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism*; D012229:Rhinovirus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D012703:Serotyping; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism
D011973:Receptors, LDL; D011991:Receptors, Virus; D014764:Viral Proteins; C074995:viral protein 1, rhinovirus