Within-host variation of avian influenza viruses

Iqbal, Munir; Xiao, Hiaxia; Baillie, Gregory J.; Warry, Andrew; Essen, Steve; Löndt, Brandon Z.; Brookes, Sharon M.; Brown, Ian H.; McCauley, John W.

doi:10.1098/rstb.2009.0088

Cited by 28 publications

(25 citation statements)

References 26 publications

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“…Although the level of intra-host diversity we report for ZYMV (mean = 0.02%) is on average less than that recently observed in intra-host studies of animal influenza viruses using similar methodologies, there was considerable overlap among estimates and fewer clones were analyzed in this case (Hoelzer et al, 2010; Iqbal et al, 2009; Murcia et al, 2010). For example, a study of 2366 sequences of equine influenza virus resulted in a mean intra-host diversity of 0.04% (range 0.01 – 0.12% among samples) (Murcia et al 2010).…”

Section: Discussioncontrasting

confidence: 80%

Rapid turnover of intra-host genetic diversity in Zucchini yellow mosaic virus

2011

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Genetic diversity in RNA viruses is shaped by a variety of evolutionary processes, including the bottlenecks that may occur at inter-host transmission. However, how these processes structure genetic variation at the scale of individual hosts is only partly understood. We obtained intra-host sequence data for the coat protein (CP) gene of Zucchini yellow mosaic virus (ZYMV) from two horizontally transmitted populations -one via aphid, the other without -and with multiple samples from individual plants. We show that although mutations are generated relatively frequently within infected plants, attaining similar levels of genetic diversity to that seen in some animal RNA viruses (mean intra-sample diversity of 0.02%), most mutations are likely to be transient, deleterious, and purged rapidly. We also observed more population structure in the aphid transmitted viral population, including the same mutations in multiple clones, the presence of a sub-lineage, and evidence for the short-term complementation of defective genomes.

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Section: Discussioncontrasting

confidence: 80%

Rapid turnover of intra-host genetic diversity in Zucchini yellow mosaic virus

2011

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“…The frequency of individual mutations at any nucleotide site was only 1.8 ϫ 10 Ϫ4 , which is similar to that observed by Iqbal et al (17) where within-host variability of avian influenza viruses was assessed in vivo using a variety of avian species. However, because our sampling depth allowed consistent detection of only the more common (Ͼ5 to 10% of the population) variants, it is likely that greater variation exists at a lower frequency than is reported here.…”

Section: Vol 84 2010supporting

confidence: 69%

Intra- and Interhost Evolutionary Dynamics of Equine Influenza Virus

Murcia

Baillie

Daly

et al. 2010

J Virol

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113

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Determining the evolutionary basis of cross-species transmission and immune evasion is key to understanding the mechanisms that control the emergence of either new viruses or novel antigenic variants with pandemic potential. The hemagglutinin glycoprotein of influenza A viruses is a critical host range determinant and a major target of neutralizing antibodies. Equine influenza virus (EIV) is a significant pathogen of the horse that causes periodical outbreaks of disease even in populations with high vaccination coverage. EIV has also jumped the species barrier and emerged as a novel respiratory pathogen in dogs, canine influenza virus. We studied the dynamics of equine influenza virus evolution in horses at the intrahost level and how this evolutionary process is affected by interhost transmission in a natural setting. To this end, we performed clonal sequencing of the hemagglutinin 1 gene derived from individual animals at different times postinfection. Our results show that despite the population consensus sequence remaining invariant, genetically distinct subpopulations persist during the course of infection and are also transmitted, with some variants likely to change antigenicity. We also detected a natural case of mixed infection in an animal infected during an outbreak of equine influenza, raising the possibility of reassortment between different strains of virus. In sum, our data suggest that transmission bottlenecks may not be as narrow as originally perceived and that the genetic diversity required to adapt to new host species may be partially present in the donor host and potentially transmitted to the recipient host.

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“…A single-nucleotide change was observed in 2 of the 5 genes that were compared (data not shown), suggesting that the cloning steps did not contribute significantly to the observed sequence variation. A previous study that addressed the within-host variation of avian influenza viruses in individually infected birds generated similar concerns regarding the error rates associated with the reverse transcription and PCR amplification steps (11). These authors utilized a two-step RT-PCR that targeted the HA and NS gene segments on RNA that was extracted directly from swab specimens collected from experimentally infected turkeys, chickens, and ducks.…”

Section: Discussionmentioning

confidence: 99%