Molecular characterization and distinguishing features of a novel human rhinovirus (HRV) C, HRVC-QCE, detected in children with fever, cough and wheeze during 2003

Abstract

Background: Human rhinoviruses (HRVs) are associated with more acute respiratory tract infections than any other viral group yet we know little about viral diversity, epidemiology or clinical outcome resulting from infection by strains, in particular the recently identified HRVs.

Objectives: To determine whether HRVC-QCE was a distinct HRV-C strain, by determining its genome and prevalence, by cataloguing genomic features for strain discrimination and by observing clinical features in positive patients.

Study design: Novel real-time RT-PCRs and retrospective chart reviews were used to investigate a well-defined population of 1247 specimen extracts to observe the prevalence and the clinical features of each HRV-QCE positive case from an in- and out-patient pediatric, hospital-based population during 2003. An objective illness severity score was determined for each HRVC-QCE positive patient.

Results: Differences in overall polyprotein and VP1 binding pocket residues and the predicted presence of a cis-acting replication element in 1B defined HRVC-QCE as a novel HRV-C strain. Twelve additional HRVC-QCE detections (1.0% prevalence) occurred among infants and toddlers (1-24 months) suffering mild to moderate illness, including fever and cough, who were often hospitalized. HRVC-QCE was frequently detected in the absence of another virus and was the only virus detected in three (23% of HRVC-QCE positives) children with asthma exacerbation and in two (15%) toddlers with febrile convulsion.

Conclusions: HRVC-QCE is a newly identified, genetically distinct HRV strain detected in hospitalized children with a range of clinical features. HRV strains should be independently considered to ensure we do not overestimate the HRVs in asymptomatic illness.

Fig. 1

Alignment of HRV amino acids in the regions that are known to interact with ICAM-1. A circular representation of HRV strains (some strain titles removed for clarity) created from a set of discontinuous VP3 and VP1 amino acids reflecting the ICAM-1 footprint. Nucleotide and amino acid alignments using Muscle (64 iterations) were created in Geneious Pro 4.7. Neighbour-joining consensus trees constructed in Mega 4.1 were used to infer phylogeny.

Fig. 2

Alignment of the 25 key VP1 amino acids making contact with pleconaril. Representative HRV-A, -B and -C strains were included. The consensus amino acid sequence and a graphical representation of the contribution of residues occupying each position are shown above the alignment. Consensus residue numbering is from Ref. .

Fig. 3

Alignment of complete VP1 coding sequences. Complete VP1 sequences of known HRV-A, -B, -C and representative HEV strains (those included in Palmenberg et al.; f-field strain). The HRVC-QCE (GenBank accession number GQ323774 and bankit numbers, 1304337, 1304336, 1304343, 1304341, 1304344, 1304335, 1304320) and HRVC-QPM strain variants are indicated with three-digit numbers. Phylogeny was inferred by using MEGA 4.1. Evolutionary distances are in the units of the number of amino acid substitutions per site (243 positions in the final dataset). Rooted on the midpoint. Only early bootstrap (n = 500) support values are shown. PV = Human Poliovirus, CV-A = Coxsackievirus A.