Limits...
Distinguishing molecular features and clinical characteristics of a putative new rhinovirus species, human rhinovirus C (HRV C).

McErlean P, Shackelton LA, Andrews E, Webster DR, Lambert SB, Nissen MD, Sloots TP, Mackay IM - PLoS ONE (2008)

Bottom Line: In silico comparisons confirmed that HRV-QPM was most closely related to the major group HRVs.These observations contributed to an objective clinical impact ranging from mild to severe.The divergent strains did not meet classification requirements for any existing species of the genus Rhinovirus or Enterovirus.

View Article: PubMed Central - PubMed

Affiliation: Queensland Paediatric Infectious Diseases Laboratory, Sir Albert Sakzewski Virus Research Centre, Royal Children's Hospital, Brisbane, Queensland, Australia.

ABSTRACT

Background: Human rhinoviruses (HRVs) are the most frequently detected pathogens in acute respiratory tract infections (ARTIs) and yet little is known about the prevalence, recurrence, structure and clinical impact of individual members. During 2007, the complete coding sequences of six previously unknown and highly divergent HRV strains were reported. To catalogue the molecular and clinical features distinguishing the divergent HRV strains, we undertook, for the first time, in silico analyses of all available polyprotein sequences and performed retrospective reviews of the medical records of cases in which variants of the prototype strain, HRV-QPM, had been detected.

Methodology/principle findings: Genomic analyses revealed that the six divergent strains, residing within a clade we previously called HRV A2, had the shortest polyprotein of all picornaviruses investigated. Structure-based amino acid alignments identified conserved motifs shared among members of the genus Rhinovirus as well as substantive deletions and insertions unique to the divergent strains. Deletions mostly affected regions encoding proteins traditionally involved in antigenicity and serving as HRV and HEV receptor footprints. Because the HRV A2 strains cannot yet be cultured, we created homology models of predicted HRV-QPM structural proteins. In silico comparisons confirmed that HRV-QPM was most closely related to the major group HRVs. HRV-QPM was most frequently detected in infants with expiratory wheezing or persistent cough who had been admitted to hospital and required supplemental oxygen. It was the only virus detected in 65% of positive individuals. These observations contributed to an objective clinical impact ranging from mild to severe.

Conclusions: The divergent strains did not meet classification requirements for any existing species of the genus Rhinovirus or Enterovirus. HRV A2 strains should be partitioned into at least one new species, putatively called Human rhinovirus C, populated by members detected with high frequency, from individuals with respiratory symptoms requiring hospital admission.

Show MeSH

Related in: MedlinePlus

Neighbour-joining phylogeny based on representative full-length picornavirus polyprotein sequences.Trees are unrooted and relevant nodes are labelled with bootstrap values (%) (see materials and methods for details). Species are indicated next to vertical bars. CV-Coxsackievirus A; EV-Echovirus; HEV-Enterovirus; HPV-Poliovirus.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2268738&req=5

pone-0001847-g006: Neighbour-joining phylogeny based on representative full-length picornavirus polyprotein sequences.Trees are unrooted and relevant nodes are labelled with bootstrap values (%) (see materials and methods for details). Species are indicated next to vertical bars. CV-Coxsackievirus A; EV-Echovirus; HEV-Enterovirus; HPV-Poliovirus.

Mentions: Previously, phylogenies had been estimated using subgenomic sequences from HRV A2-like strains [31]–[33]. To test whether this approach accurately represented inter-strain relationships, we compared the entire polyprotein sequences from 120 previously described and, for the first time, all six newly-identified picornavirus strains (Figure 6). We confirmed that the newly-identified HRVs occupy a distinct phylogenetic position with the genus Rhinovirus [34] and are most closely related to the HRV A strains (also supported by SimPlot mapping; Figure 3). We also found support for our earlier data [31] that this clade is divided into two distinct subgroups. In the 2C and 3CD regions, these subgroups share less than 70% amino acid identity, which also occurs among members of the existing HRV species.


Distinguishing molecular features and clinical characteristics of a putative new rhinovirus species, human rhinovirus C (HRV C).

McErlean P, Shackelton LA, Andrews E, Webster DR, Lambert SB, Nissen MD, Sloots TP, Mackay IM - PLoS ONE (2008)

Neighbour-joining phylogeny based on representative full-length picornavirus polyprotein sequences.Trees are unrooted and relevant nodes are labelled with bootstrap values (%) (see materials and methods for details). Species are indicated next to vertical bars. CV-Coxsackievirus A; EV-Echovirus; HEV-Enterovirus; HPV-Poliovirus.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2268738&req=5

pone-0001847-g006: Neighbour-joining phylogeny based on representative full-length picornavirus polyprotein sequences.Trees are unrooted and relevant nodes are labelled with bootstrap values (%) (see materials and methods for details). Species are indicated next to vertical bars. CV-Coxsackievirus A; EV-Echovirus; HEV-Enterovirus; HPV-Poliovirus.
Mentions: Previously, phylogenies had been estimated using subgenomic sequences from HRV A2-like strains [31]–[33]. To test whether this approach accurately represented inter-strain relationships, we compared the entire polyprotein sequences from 120 previously described and, for the first time, all six newly-identified picornavirus strains (Figure 6). We confirmed that the newly-identified HRVs occupy a distinct phylogenetic position with the genus Rhinovirus [34] and are most closely related to the HRV A strains (also supported by SimPlot mapping; Figure 3). We also found support for our earlier data [31] that this clade is divided into two distinct subgroups. In the 2C and 3CD regions, these subgroups share less than 70% amino acid identity, which also occurs among members of the existing HRV species.

Bottom Line: In silico comparisons confirmed that HRV-QPM was most closely related to the major group HRVs.These observations contributed to an objective clinical impact ranging from mild to severe.The divergent strains did not meet classification requirements for any existing species of the genus Rhinovirus or Enterovirus.

View Article: PubMed Central - PubMed

Affiliation: Queensland Paediatric Infectious Diseases Laboratory, Sir Albert Sakzewski Virus Research Centre, Royal Children's Hospital, Brisbane, Queensland, Australia.

ABSTRACT

Background: Human rhinoviruses (HRVs) are the most frequently detected pathogens in acute respiratory tract infections (ARTIs) and yet little is known about the prevalence, recurrence, structure and clinical impact of individual members. During 2007, the complete coding sequences of six previously unknown and highly divergent HRV strains were reported. To catalogue the molecular and clinical features distinguishing the divergent HRV strains, we undertook, for the first time, in silico analyses of all available polyprotein sequences and performed retrospective reviews of the medical records of cases in which variants of the prototype strain, HRV-QPM, had been detected.

Methodology/principle findings: Genomic analyses revealed that the six divergent strains, residing within a clade we previously called HRV A2, had the shortest polyprotein of all picornaviruses investigated. Structure-based amino acid alignments identified conserved motifs shared among members of the genus Rhinovirus as well as substantive deletions and insertions unique to the divergent strains. Deletions mostly affected regions encoding proteins traditionally involved in antigenicity and serving as HRV and HEV receptor footprints. Because the HRV A2 strains cannot yet be cultured, we created homology models of predicted HRV-QPM structural proteins. In silico comparisons confirmed that HRV-QPM was most closely related to the major group HRVs. HRV-QPM was most frequently detected in infants with expiratory wheezing or persistent cough who had been admitted to hospital and required supplemental oxygen. It was the only virus detected in 65% of positive individuals. These observations contributed to an objective clinical impact ranging from mild to severe.

Conclusions: The divergent strains did not meet classification requirements for any existing species of the genus Rhinovirus or Enterovirus. HRV A2 strains should be partitioned into at least one new species, putatively called Human rhinovirus C, populated by members detected with high frequency, from individuals with respiratory symptoms requiring hospital admission.

Show MeSH
Related in: MedlinePlus