Thursday, 12 September 2013

Happy Birthday rhinoviruses (RVs) - 60 years old today!

Predicted capsid model of HRV-QPM (Q=Queensland;
PM-initials of the then PhD student who did all the work).
This distinct virus is now known as HRV-C3.
It was the first HRV-C type to be sequenced,
clinically, epidemiologically and virologically
characterised and modelled. It was the third HRV-C
polyprotein sequence to be placed on  GenBank.
On September 12th 1953, the Common Cold Unit (CCU, Salisbury, United Kingdom) reported isolating the agent of the common cold in laboratory cultures. The article was authored by Dr (later Sir)Christopher Andrewes and colleagues in The Lancet.

The isolate, called D.C. after Dr Donna M. Chaproniere's donated cold sample, was only able to be grown while the lung tissue from a particular embryo remained. Once stock was exhausted, the viral culture failed. The D.C. type was not able to be characterized until 1968, by which time another variant of that type had already be given a name; RV-9.


More reliable, repeatable RV culture were achieved in 1956 Price et al (the JH type) and 1957 by Pelon et al (the 2060 type). Back at the CCU, it was found that increasing the acidity, lowering temperatures and rotating the cultures increased the success of virus isolation. The use of increased acidity was discovered by accident when CCU's Dr David Tyrrell had to replace some medium that was killing his cultures. He borrowed (as we do) others' stocks to tide him over. During this process he noted a sign of viral replication  his cultures were being killed  He eventually deduced it was because of the acidity of the new medium compared to his previous work.


 21,915 days later there have been a number of interesting developments to come from the study of RVs:

  • type is the name for a distinct RV; that type found in another patient anywhere around the world is called a variant of the type. Specific criteria now exist to define types and variants, and to identify a new HRV type.
  • Recently, HRVs became RVs - the host bit was dropped but their individual names remain "HRV" and they now have the species name included e.g. HRV-A1
  • There are >150 distinct RV types
  • As many as 70 RV types can circulate at a single site at one study period
  • The early RVs were initially classified as echoviruses (ECHO-28; later RV-1) and have also been called ERC viruses, muriviruses, Salisbury strains, coryzaviruses and enterovirus-like viruses
  • RV-Cs do not grow using any routinely used cell culture lines, but can be grown in primary tissues and differentiated multilayer cell cultures at the air-liquid interface
  • RVs are the most frequent virus to be detected in children and adults with acute upper respiratory tract infections including the "common cold"
  • RV infection of adult chronic obstructive pulmonary disease ( COPD) patients may precipate outgrowth of Haemophilus influenzae, not seen among healthy RV infectees
  • RVs are also associated with fever and influenza-like illness (ILI), where and they can be near impossible to discriminate from some ILIs without laboratory testing
  • RVs are the viruses most frequently detected in wheezing exacerbations ("attacks") in those with asthma where they, more than any other virus, seem to take advantage of antiviral immune deficiencies. While RV-Cs appear to be more exacerbatory, I personally believe this is just an artefact of small, short studies
  • RVs are found more often than other viruses in people without overt signs of respiratory disease; but as a proportion of all viruses, RVs are less often found in well people compared to most other respiratory viruses. 
  • RVs do not persist (a given RV type is not detected beyond 2-4 weeks) except in those with serious immune deficiency such as those undergoing lung transplant
  • There used to be a genus Rhinovirus, but that was abolished and now the three RV species (A, B, C) sit under the genus Enterovirus
  • There is no vaccine or broadly available antiviral for HRVs although both are being actively researched now.
  • Prior to the use of PCR to detect RVs in 1988/1989, epidemiology studies looking at the impact of a specific respiratory could not account for 50+ HRV-Cs (and perhaps some fastidious HRV-As and Bs)
  • RV-Bs are considered "wimps" by those in the know and they are always under-represented when found i.e they appear to circulate in smaller numbers than chance would dictate they should
So, many happy returns little guys. Long may you educate our immune systems with your constant challenges, long may you interfere with the seasons of other viruses and long may you make me write silly titles for reviews when under your mind-altering influence (that's my excuse anyway). 

Much may have been written about other respiratory viruses over the years, but the HRVs are always with us, always challenging us and always causing problems for us. To study RVs is to study all respiratory viruses and diseases of the upper and lower respiratory tract. To exclude them from study or test is to fail to understand these diseases.

Some literature...

  1. Hilding,A. The Common Cold. Arch Otolaryngol. Head Neck Surg. 12, 133-150 (1930). 
  2. Tyrrell,D.A.J. & Fielder,M. Cold wars: The fight against the common cold (Oxford University Press, New York, 2002).
  3. Propagation of common-cold virus in tissue cultures.
  4. Outgrowth of the Bacterial Airway Microbiome following Rhinovirus Exacerbation of Chronic Obstructive Pulmonary Disease
  5. Newly identified respiratory viruses in children with asthma exacerbation not requiring admission to hospital.
  6. Newly identified human rhinoviruses: molecular methods heat up the cold viruses.
  7. Human rhinoviruses: coming in from the cold.
  8. Do rhinoviruses reduce the probability of viral co-detection during acute respiratory tract infections?
  9. Molecular characterization and distinguishing features of a novel human rhinovirus (HRV) C, HRVC-QCE, detected in children with fever, cough and wheeze during 2003.
  10. Prior evidence of putative novel rhinovirus species, Australia.
  11. Human rhinoviruses: the cold wars resume.
  12. Distinguishing molecular features and clinical characteristics of a putative new rhinovirus species, human rhinovirus C (HRV C).
  13. Frequent detection of human rhinoviruses, paramyxoviruses, coronaviruses, and bocavirus during acute respiratory tract infections.