Clinical and molecular features of human rhinovirus C

Abstract

A newly discovered group of human rhinoviruses (HRVs) has been classified as the HRV-C species based on distinct genomic features. HRV-Cs circulate worldwide, and are important causes of upper and lower respiratory illnesses. Methods to culture and produce these viruses have recently been developed, and should enable identification of unique features of HRV-C replication and biology.

Fig. 1

HRV-C genome organization and distinct features. (A) Schematic representation of the HRV-C genome encoding single polyprotein open reading frame, flanked by 5’- and 3’-UTRs. Indicated nucleotide positions correspond to HRV-C15 complete genome sequence (GenBank accession number GU219984). HRV-C-specific genomic features are shown in green. (B) Structural motifs predicted from HRV-C15 genomic RNA and their genomic locations.

Fig. 2

Neighbor-joining phylogenetic tree based on partial 1A/1B (VP4/VP2) nucleotide sequences (positions 608–1002 of HRV-C15 complete genome, accession number GU219984) of all sequenced types of HRV-C species, and representatives of major branches of HRV-A and HRV-B species, constructed using MEGA 4.1 software [78]. All major nodes are labeled with bootstrap values (1000 replicates, with its value more than 70%). Branch lengths are proportional to nucleotide similarity (p-distance). Human enteroviruses (polio- and coxsackieviruses) are included as an outgroup. HRV-C types followed by GenBank accession numbers correspond to the recent classification proposal [59]. Fully-sequenced (genomes or ORFs) and provisionally assigned (pat) HRV-C types are shown by filled and open diamonds, respectively.

Fig. 3

Putative interspecies recombination in HRV-C 5’-UTR. Similarity plot (A) and bootscanning (B) analyses of the HRV-C7 strain NY-074 (GenBank accession number DQ875932) implemented by the RDP and Bootscan methods (window size 200, step size 20, 1000 replicates), respectively, in RDP3.31 show the predicted recombination crossover site in 5’-UTR. Phylogenetic trees constructed from (C) the putative recombinant sequence (5’-UTR positions 150–594) and (D) the rest of genome reveals incongruent clustering of recombinant strain. Parental strains are shown by red (HRV-A) and green (HRV-C) colors, and the recombinant strain is shaded in green.