Darwinian principles acting on highly mutable viruses

Domingo, Esteban

doi:10.1016/b978-0-12-816331-3.00003-9

Cited by 2 publications

(3 citation statements)

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“…Notably, a higher relative fitness and increased replication level may translate into higher excreted virus doses during infection. If higher doses are transmitted on average, this will inevitably increase the viral capability to adapt to humans [30,36]. In addition, reduced cytokine induction is often considered to be an indicator of increased virulence.…”

Section: Discussionmentioning

confidence: 99%

“…Cell culture growth kinetics can suffer from systematic and random errors, parts of which can be controlled for by competitive replication studies in which viral isolates compete in one same culture dish. A given virus is likely to have superior relative fitness if it can become dominant in a virus population in spite of starting as a minority population in the initial virus seed dose used for infection [30]. To test this, Calu-3 cells were infected with a mixture of representative virus of lineage 5 and lineage 3 in two different ratios (1 : 1 and 9 : 1; lineage 3 : lineage 5).…”

Section: Competitive Replicative Fitnessmentioning

confidence: 99%

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Functional comparison of MERS-coronavirus lineages reveals increased zoonotic potential of the recombinant lineage 5

Schroeder

Mache

Kleine-Weber

et al. 2020

Preprint

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Middle East respiratory syndrome coronavirus (MERS-CoV) can cause severe pneumonia in humans. The virus is enzootic in dromedary camels across the Middle East and Africa. It is acquired through animal contact and undergoes limited onward transmission particularly in hospitals. Because of this initial potential for human-to-human transmission, we monitor the virus for phenotypic changes related to its pandemic potential. Potential phenotypic changes have been suspected since the year 2015, when a novel recombinant clade (MERS-CoV lineage 5) caused large nosocomial outbreaks in Saudi Arabia and South Korea that effectively swept other, hitherto co-circulating viral lineages. To this day, lineage 5 remains the only circulating MERS-CoV lineage on the Arabian Peninsula. In spite of available sequence data, no studies of viral phenotype have been carried out to date. Here we performed a comprehensive in-vitro and ex-vivo comparison of live virus isolates taken in Saudi Arabia immediately before and after the shift toward lineage 5. We characterized seven isolates representing the recombination-parental lineage 3, eight isolates representing parental lineage 4, as well as eight isolates representing lineage 5. Replication of lineage 5 viruses is significantly increased over isolates from parental lineages in cell culture and ex-vivo lung models. Transcriptional profiling by real-time RT-PCR shows that several key immune genes (IFNb1, CCL5, IFNL1) are significantly less induced in lung cells infected with lineage 5 MERS-CoV compared to parental strains. In IFN receptor knock out cells, as well as under chemical inhibition of IFN signalling, the differences in replication level between lineage 5 and parental lineages are reduced, suggesting that phenotypic differences may be determined by IFN antagonism. Concordantly, lineage 5 shows increased resilience against interferon (IFN) pre-treatment of Calu-3 cells and maintains a 10-fold higher replication level under low and high concentrations of IFN. Reduced immune activation combined with enhanced virus replication and IFN resilience may explain the dominance of lineage 5 on the Arabian Peninsula. This phenotypic difference is highly relevant with regard to pandemic potential, and has remained undiscovered in spite of viral sequence surveillance.

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Section: Discussionmentioning

confidence: 99%

Section: Competitive Replicative Fitnessmentioning

confidence: 99%

Functional comparison of MERS-coronavirus lineages reveals increased zoonotic potential of the recombinant lineage 5

Schroeder

Mache

Kleine-Weber

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Typically, a ratio > 1 could be qualified as "positive selection" and, due to the biological function of this region, could represent evidence of preferential selection of variants with changes in T cell-directed epitopes to evade immune detection or either due to replication advantages. Alternatively, they could represent transient deleterious mutations that are tolerated by this simple coding region in a low selective pressure environment, rather than a real positive selection (Domingo, 2015;Pybus et al, 2007;Torres et al, 2013).…”

Section: Discussionmentioning

confidence: 99%