The most amazing thing about the “common cold”, or at least, the proportion of this spectrum of diseases which is caused by rhinoviruses (as opposed to adenoviruses, coronaviruses, or something else), is how little we still know about it. A few years ago I was involved in a proposal for a large project which would look at some of the issues adressed by a new research paper which has just appeared. That proposal eventually collapsed under its own weight, so it’s fascinating to read these new results and see what we might have found.
The new study describes a phylogenetic analysis to compare the relative distribution of HRV species or serotypes according to the respiratory site (upper respiratory tract (URT) versus lower respiratory tract (LRT) ) and in protracted infection in hospital patients and immunosuppressed lung transplant recipients. In one case, rhinovirus genome variation was followed in the URT and LRT over a period of 27 months using both classical and ultra-deep sequencing methods.
Based on phylogenetic analysis, the frequency distribution of strains infecting the URT and LRT did not reveal any apparent correlation between a given HRV serotype or species and their ability to infect the LRT. Five lung transplant recipients were chronically infected with HRV during periods of time ranging from three to 27 months. Mutation mapping along the HRV genome showed that synonymous changes were roughly spread along the entire ORF, whereas non-synonymous changes clustered mostly in the capsid VP2, VP3, and VP1 genes. The capsid genes are also the most variable during acute infections in immunocompetent hosts.
As expected, the data suggests that immunocompromised patients cannot clear virus infections as well as immunocompetent individuals, and represent a potential reservoir for the emergence of new variants and inter-host transmission due to chronic virus infection. In addition, these patients may be co-infected by two viruses, thus opening the door to recombination, another putative driving force of rhinovirus evolution. With the emergence of new therapies and progress in transplantation, the population of immunocompromised patients is constantly increasing. Our results suggest that this could accelerate the ability of viruses to adapt to the host, evolve, and propagate and may favor a more rapid emergence of new viral variants.
Rhinovirus Genome Variation during Chronic Upper and Lower Respiratory Tract Infections. (2011) PLoS ONE 6(6): e21163. doi:10.1371/journal.pone.0021163
Routine screening of lung transplant recipients and hospital patients for respiratory virus infections allowed to identify human rhinovirus (HRV) in the upper and lower respiratory tracts, including immunocompromised hosts chronically infected with the same strain over weeks or months. Phylogenetic analysis of 144 HRV-positive samples showed no apparent correlation between a given viral genotype or species and their ability to invade the lower respiratory tract or lead to protracted infection. By contrast, protracted infections were found almost exclusively in immunocompromised patients, thus suggesting that host factors rather than the virus genotype modulate disease outcome, in particular the immune response. Complete genome sequencing of five chronic cases to study rhinovirus genome adaptation showed that the calculated mutation frequency was in the range observed during acute human infections. Analysis of mutation hot spot regions between specimens collected at different times or in different body sites revealed that non-synonymous changes were mostly concentrated in the viral capsid genes VP1, VP2 and VP3, independent of the HRV type. In an immunosuppressed lung transplant recipient infected with the same HRV strain for more than two years, both classical and ultra-deep sequencing of samples collected at different time points in the upper and lower respiratory tracts showed that these virus populations were phylogenetically indistinguishable over the course of infection, except for the last month. Specific signatures were found in the last two lower respiratory tract populations, including changes in the 5′ UTR polypyrimidine tract and the VP2 immunogenic site 2. These results highlight for the first time the ability of a given rhinovirus to evolve in the course of a natural infection in immunocompromised patients and complement data obtained from previous experimental inoculation studies in immunocompetent volunteers.