Intrahost evolutionary dynamics of canine influenza virus in naive and partially immune dogs

Abstract

The patterns and dynamics of evolution in acutely infecting viruses within individual hosts are largely unknown. To this end, we investigated the intrahost variation of canine influenza virus (CIV) during the course of experimental infections in naïve and partially immune dogs and in naturally infected dogs. Tracing sequence diversity in the gene encoding domain 1 of the hemagglutinin (HA1) protein over the time course of infection provided information on the patterns and processes of intrahost viral evolution and revealed some of the effects of partial host immunity. Viral populations sampled on any given day were generally characterized by mean pairwise genetic diversities between 0.1 and 0.2% and by mutational spectra that changed considerably on different days. Some observed mutations may have affected antigenicity or host range, including reversions of CIV host-associated mutations. Patterns of sequence diversity differed between naïve and vaccinated dogs, with some presumably antigenic mutations transiently reaching high frequency in the latter. CIV populations are therefore characterized by the rapid generation and clearance of genetic diversity. Potentially advantageous mutations arise readily during the course of single infections and may give rise to antigenic escape or host range variants.

FIG. 1.

Minimum spanning trees of the challenge virus (yellow) and virus sequences isolated from the two naïve dogs (dog 8271 [light, medium, and dark blue]) and dog 7151 [pink, red, and brown] on days 2 to 4 postinoculation. Mutations (except for singletons) are indicated on the respective branches, and nonsynonymous mutations are indicated in bold type. The size of each circle is proportional to the number of sequences representing the node. Hypothetical nodes are indicated by broken lines. SP, mutation located in signal peptide.

FIG. 2.

Minimum spanning trees of the challenge virus (yellow) and virus sequences isolated from the two vaccinated dogs (dog 5981 [light and dark blue] and dog 6685 [red and brown]) on days 2 and 3 postinoculation. Mutations (except for singletons) are indicated on the respective branches, and nonsynonymous mutations are indicated in bold type. The size of each circle is proportional to the number of sequences representing the node. Hypothetical nodes are indicated by broken lines. SP, mutation located in signal peptide.