Evolutionary Processes Shaping Human Rhinovirus Lineages

Abstract

Human rhinovirus (HRV) is a single-stranded RNA virus, which causes upper respiratory infections and exacerbations of asthma and chronic obstructive pulmonary disease. Little is known about the evolution of the virus, the basis for >100 types (lineages), or if these lineages cause different clinical phenotypes. Methods were developed to sequence known and unknown HRV genomes in their entirety and were applied to the study of HRVs of the same lineage within a single cold season in one geographical area, very short-term transmission between individuals, and archived samples suggestive of novel lineages. Once sequence was available, analyses of the evolution of HRV were undertaken. Here, it is demonstrated that HRV genomes are shaped according to a quasispecies model. HRVs replicate in hosts producing swarms of viral genomes. The genomes constituting the viral swarms appear to be produced by host-virus interactions during replication causing mutations, insertions and deletions, and recombination events. Upon passage to a new host, shifts in the distribution of the variant genomes within the swarm are observed. The ability of an infecting HRV viral swarm to shift its genome distribution may provide increased functionality and thus maximal survival. Given the observed overall flexibility, it will be important to determine if there are relatively stable regions of the genomes within the viral swarm that could provide novel targets for therapy.