When times are good or bad, happy or sad, viral quasispecies like to stay together

Image courtsey of the Wikipedia article on coral reef fish, aka Nemo and the sea anemone

Image courtsey of the Wikipedia article on coral reef fish, aka Nemo and the sea anemone

We’ve known for a long time that symbioses are important across all walks of life. Clownfish and sea anemones are obligate symbionts, and bacteria found in legume root nodules help fix nitrogen. In a nice review published recently in Evolutionary Biology (Supp 2016), Jan Supp emphasizes the importance of understanding microbial symbiosis, and how these interactions are linked to development and evolution, in particular in relation to health and disease. Recently developed molecular methods have allowed for a better understanding of how microbes influence our health.

RNA viruses mutate fast and exist in highly diverse populations composed of what are referred to as “quasispecies”. The existence of these genetic variants is thought to promote population fitness. The findings from Xue et al., published today in eLife, present an elegant example of how the fitness of a H3N2 influenza population is enhanced when diverse variants (eg. multiple quasispecies) are present. This study demonstrates how looking at population dynamics (such as selection) are essential in understanding genomic evolution.

Residue 151 in the neuraminidase (NA) has made a name for itself, because it is located in the active site of the protein, which is involved in viral exit from host cells. Plenty o’ studies have found that mutations happen often when H3N2 is kept in cell culture, and the rate of mutation is higher in viruses passaged in cell culture vs original clinical isolates.

Ambiguous identities are common at NA site 151 after 2007.

Ambiguous identities are common at NA site 151 after 2007.

The authors show that starting in 2007, frequency of mutations at NA site 151 (with aspartic acid (D) or glycine (G) at site 151). jumped to 25% of the population, and as the figure demonstrates this is the case really just in the viruses maintained in cell cultures…but why? The mutation ends up in mixed populations, but the question still exists: are the mixed populations just a snapshot of a population that hasn’t quite reached fixation? Using two isogenic strains created with reverse genetics, the group looked at the two quasispecies and found that the mixed populations consistently had the best growth rates. Furthermore, when pure populations were cultured, mutations at residue 151 arose spontaneously.

Mixed populations grow to higher titers than either pure population alone.

Mixed populations grow to higher titers than either pure population alone.

Serial passage selects for a stable mix of the two variants.

Serial passage selects for a stable mix of the two variants.

Monitoring allele frequency after serial passages demonstrated that selection balances the proportion of the genotypes in the population. Finally, they also demonstrate that this cooperation isn’t just beneficial, but required when the hemagglutinin (HA) protein lacks receptor-binding activity. Cooperation is the key! Since it turns out that one variant is good at cell entry, and the other at cell exit, together they can infect cells more efficiently. There is no “I” in team…turns out there is a G and a D…..The work here suggests that cooperation is necessary to enhance the fitness of this virus. The authors stated:

“Our work emphasizes that genetic diversity in viral populations can be more than a transient state that facilitates adaptation: it can itself be a beneficial trait that is generated and maintained by selection.” – Xue et al., 2016

This is just the first step towards determining if these two variants cooperate in clinical infections. While results from previous studies might be biased since they are not so good at picking up low-frequency variants, future efforts promise to provide new insights into our developing view of how holobionts function and evolve.

References

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About Kelle Freel

I'm currently a postdoc working at the Hawai'i Institute of Marine Biology with Dr. Mike Rappé. I'm interested in the biogeography and ecology of microbes, especially of the marine variety. After studying a unique genus of marine bacteria at Scripps Oceanography in grad school, I moved to France, where I worked with a group studying yeast population genomics. In my free time, I like to do outdoorsy stuff, travel, and cook.
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