Wednesday, 1 April 2015

Rhinoviruses (RVs)...a primer

Schematic of a human rhinovirus (RV) genome. (+)ssRNA genome.
Based on GenBank accession no. NC_001490 for HRV-C3 (f.QPM).
Use images freely but please cite 
and Dr. Ian M Mackay as their source.
Click on image to enlarge
More than 100 serologically distinct types (serotypes), and another 50 or more genotypically defined and distinct types (genotypes) of human rhinovirus (RV; Greek rhin = nose) exist within the genus Enterovirus. Along with other members of the family Picornaviridae, the RVs are unenveloped viruses with a positive sense, single-stranded RNA genome that is preceded by a genome-linked protein (5' VPg) and terminated with a poly(A) tract (3').

Other genera within the family include Aphthovirus, Aquamavirus, Avihepatovirus, Cardiovirus, Cosavirus, Dicipivirus, Enterovirus, Erbovirus, Hepatovirus, Kobuvirus, Megrivirus, Parechovirus, Salivirus, Sapelovirus, Senecavirus, Teschovirus and Tremovirus.

HRV discovery...

Click on image to enlarge.
The first rhinovirus to be isolated in cell culture was at the Common Cold Unit (Salisbury, UK).[4] By 1967, 55 serologically distinct (sero)types had been recognized. In 2006 the first report[3] defining a distinct genetic grouping of RV types not previously recognized by Mackay and colleagues contributed to the addition of 50 more distinct types assigned to a new species, RV-C. In 2014, a number of additional RV genomes, as well as known ones, were sequenced and published.[7,8,9]

HRV taxonomy: a tale of types and variants...

Predictive capsid model of a rhinovirus C virion (RV-C3, f.QPM).
3D rendering of predicted RV-C3 capsid providing imagery
similar to that obtained by cryo-electron microscopy
reconstruction at 10 Å resolution.
doi:10.1371/journal.pone.0001847.g005 [10]  
RV genotypes and serotypes are most simply referred to as "types". Keep in mind that individual types are still written as “HRV-blahblah” whereas the species shorthand or conversationally written form has dropped the “H” to leave “RV”. The 2 best RV schemes for genetically defining an RV type versus a variant of an RV type (the same RV type, but detected in another patient - very little genetic distance separates one RV variant from another in any region of the genome), have been described by Prof Peter Simmonds and colleagues.[5,6] For the latest naming development check the Picornavirus Study Group’s websites.[1,2]

HRVs and pneumonia...

Pneumonia is a disease that of the young and the elderly in particular. It is responsible for millions of deaths each year and is associated with viral and/or bacterial infections. Pneumonia requires an X-Ray confirmation of inflammatory infiltration of the lung tissue. Community-acquired pneumonia (CAP) in children is frequent in developing countries. CAP can also make existing chronic medical conditions worse and takes advantage of the ageing immune system.

HRVs play some role in the development of bacterial pneumonia, but the extent is likely to be underestimated. Determining the cause of pneumonia is made difficult by the low frequency of sampling the lower respiratory tract, by studies that are  conducted over short periods of time and by the complexity of the viral and bacterial mix involved. Quick and  easy sampling of the upper airways is ideal for routine sampling of patients. This convenience and reduced risk  associated with some sampling methods (needle aspirates for example) sampling of the lower respiratory tract  means that often, detection of putative viral or bacterial pathogens in the upper airways is assumed to be related  to LRT disease, especially in children under the age of 5 years. Studies of pneumonia studies are also  complicated by the infrequent inclusion of a control patient group and by the fact that sputum is not produced  from the healthy lower airway. 

Before PCR methods, respiratory syncytial virus (RSV) and then RVs were described as the major viral  contributors to CAP (between 1 and 2 thirds of cases). In the golden PCR age, RVs are increasingly the major  viral group detected from both upper and lower respiratory tract (sputum) specimens from children with CAP.  These findings are supported even when studies span more than a 12-month period, which should encompass  change in the prevalence of seasonal viruses. 

Viruses, including RVs, are thought to pave the way for bacterial super-infection in some direct or indirect way.  There are data from laboratory research studies which support this as well as clinical data finding a high proportion of  RV and bacterial co-detections. Despite considerable comment in the literature, rhinoviruses are in fact less likely to be co-detected with another virus, than are many other viruses.[11]
  1. Nick Knowles, Chair of the Picornavirus Study Group's excellent Picornaviridae website 
  2. The official Picornaviridae Study Group website 
  3. KE Arden et al. Frequent detection of human rhinoviruses, paramyxoviruses, coronaviruses, and bocavirus during acute respiratory tract infections. J Med Virol.  2006. 78(9):1232-40 
  4. IM Mackay, Human rhinoviruses: The cold wars resume. J Clin Virol. 2008. 42:297-320 
  5. P Simmonds and colleagues. Proposals for the classification of human rhinovirus species C into genotypically assigned types. J Gen Virol. 2010. 91(Pt 10):2409- 19
  6. CL McIntyre and colleagues. Proposals for the classification of human rhinovirus species A, B and C into genotypically assigned types. J Gen Virol. 2013  94(Pt8):1791-806
  7. Liggett and colleagues. Genome sequences of rhinovirus C isolates from Wisconsin pediatric respiratory studies. Genome Announc. 2014 2(2) e00203-14
  8. Liggett and colleagues. Genome sequences of rhinovirus B isolates from Wisconsin pediatric respiratory studies. Genome Announc. 2014 2(2) e00202-14
  9. Liggett and colleagues. Genome sequences of rhinovirus A isolates from Wisconsin pediatric respiratory studies. Genome Announc. 2014 2(2) e00200-14
  10. McErlean and colleagues. Distinguishing molecular features and clinical characteristics of a putative new rhinovirus species, human rhinovirus C (HRV C). PLoS  One. 2008 3(4):e1847
  11. Greer and colleagues. Do rhinoviruses reduce the probability of viral co-detection during acute respiratory tract infections? J Clin Virol. 2009 45(1):10-5