Effects of Transmission Bottlenecks on the Diversity of Influenza A Virus

Sigal, Daniel; Reid, Jennifer; Wahl, Lindi M.

doi:10.1534/genetics.118.301510

Cited by 20 publications

(31 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The latter possibility is further supported by our results, which showed a significantly high number of non-synonymous variants at the sub-consensus level, none of which were seen at the consensus level. Similar findings were also reported in other SARS-CoV-2 studies (Sigal et al, 2018 ; Capobianchi et al, 2020 ; Shen et al, 2020 ). Still, other research groups were able to find variability hotspots in SARS-CoV-2 genomes (Ceraolo and Giorgi, 2020 ; van Dorp et al, 2020 ).…”

Section: Discussionsupporting

confidence: 90%

Within-Host Diversity of SARS-CoV-2 in COVID-19 Patients With Variable Disease Severities

Al-Khatib

Benslimane

Elbashir

et al. 2020

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Background: The ongoing pandemic of SARS-COV-2 has already infected more than eight million people worldwide. The majority of COVID-19 patients either are asymptomatic or have mild symptoms. Yet, about 15% of the cases experience severe complications and require intensive care. Factors determining disease severity are not yet fully characterized. Aim: Here, we investigated the within-host virus diversity in COVID-19 patients with different clinical manifestations. Methods: We compared SARS-COV-2 genetic diversity in 19 mild and 27 severe cases. Viral RNA was extracted from nasopharyngeal samples and sequenced using the Illumina MiSeq platform. This was followed by deep-sequencing analyses of SARS-CoV-2 genomes at both consensus and sub-consensus sequence levels. Results: Consensus sequences of all viruses were very similar, showing more than 99.8% sequence identity regardless of the disease severity. However, the sub-consensus analysis revealed significant differences in within-host diversity between mild and severe cases. Patients with severe symptoms exhibited a significantly ( p -value 0.001) higher number of variants in coding and non-coding regions compared to mild cases. Analysis also revealed higher prevalence of some variants among severe cases. Most importantly, severe cases exhibited significantly higher within-host diversity (mean = 13) compared to mild cases (mean = 6). Further, higher within-host diversity was observed in patients above the age of 60 compared to the younger age group. Conclusion: These observations provided evidence that within-host diversity might play a role in the development of severe disease outcomes in COVID-19 patients; however, further investigations are required to elucidate this association.

show abstract

Section: Discussionsupporting

confidence: 90%

Within-Host Diversity of SARS-CoV-2 in COVID-19 Patients With Variable Disease Severities

Al-Khatib

Benslimane

Elbashir

et al. 2020

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

show abstract

“…However, it is unclear whether these intra-host variants occurred before the transmission or after the transmission, which would result in different conclusions. Additionally, a bottleneck may be involved in the transmission, which could also result in the loss of diversity [18]. Nevertheless, the observation of high mutation burden in some patients emphasized the possibility of rapid-evolving of this virus.…”

Section: Discussionmentioning

confidence: 99%

Genomic Diversity of Severe Acute Respiratory Syndrome–Coronavirus 2 in Patients With Coronavirus Disease 2019

Shen

Xiao

Kang

et al. 2020

Clinical Infectious Diseases

500

428

View full text Add to dashboard Cite

An elevated level of viral diversity was found in some SARS-CoV-2 infected patients, indicating the risk of rapid evolution of the virus. Although no evidence for the transmission of intra-host variants was found, the risk should not be overlooked. Abstract:Background A novel coronavirus (SARS-CoV-2) has infected more than 75,000 individuals and spread to over 20 countries. It is still unclear how fast the virus evolved and how the virus interacts with other microorganisms in the lung. MethodsWe have conducted metatranscriptome sequencing for the bronchoalveolar lavage fluid of eight SARS-CoV-2 patients, 25 community-acquired pneumonia (CAP) patients, and 20 healthy controls. ResultsThe median number of intra-host variants was 1-4 in SARS-CoV-2 infected patients, which ranged between 0 and 51 in different samples. The distribution of variants on genes was similar to those observed in the population data (110 sequences).However, very few intra-host variants were observed in the population as polymorphism, implying either a bottleneck or purifying selection involved in the transmission of the virus, or a consequence of the limited diversity represented in the current polymorphism data. Although current evidence did not support the transmission of intra-host variants in a person-to-person spread, the risk should not be overlooked.The microbiota in SARS-CoV-2 infected patients was similar to those in CAP, either dominated by the pathogens or with elevated levels of oral and upper respiratory commensal bacteria.Conclusion SARS-CoV-2 evolves in vivo after infection, which may affect its virulence, infectivity, and transmissibility. Although how the intra-host variant spreads in the population is still elusive, it is necessary to strengthen the surveillance of the viral Downloaded from https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciaa203/5780800 by guest on 16 March 2020 4 evolution in the population and associated clinical changes.

show abstract

“…Laboratory studies using animal models [10][11][12] show that only 3-5 amino acid substitutions may be required to render H5N1 viruses mammalian-transmissible [10][11][12], and that viral variants present at frequencies as low as 5% may be transmitted by respiratory droplets [13]. Subsequent modeling studies suggest that within-host dynamics are conducive to generating human-transmissible viruses, but that these viruses may remain at frequencies too low for transmission [14,15]. Although these studies offer critical insight for H5N1 virus risk assessment, it is unclear whether they adequately describe how cross-species transmission proceeds in nature.…”

Section: Introductionmentioning

confidence: 99%

Quantifying within-host diversity of H5N1 influenza viruses in humans and poultry in Cambodia

et al. 2020

View full text Add to dashboard Cite

Avian influenza viruses (AIVs) periodically cross species barriers and infect humans. The likelihood that an AIV will evolve mammalian transmissibility depends on acquiring and selecting mutations during spillover, but data from natural infection is limited. We analyze deep sequencing data from infected humans and domestic ducks in Cambodia to examine how H5N1 viruses evolve during spillover. Overall, viral populations in both species are predominated by low-frequency (<10%) variation shaped by purifying selection and genetic drift, and half of the variants detected within-host are never detected on the H5N1 virus phylogeny. However, we do detect a subset of mutations linked to human receptor binding and replication (PB2 E627K, HA A150V, and HA Q238L) that arose in multiple, independent humans. PB2 E627K and HA A150V were also enriched along phylogenetic branches leading to human infections, suggesting that they are likely human-adaptive. Our data show that H5N1 viruses generate putative human-adapting mutations during natural spillover infection, many of which are detected at >5% frequency within-host. However, short infection times, genetic drift, and purifying selection likely restrict their ability to evolve extensively during a single infection. Applying evolutionary methods to sequence data, we reveal a detailed view of H5N1 virus adaptive potential, and develop a foundation for studying hostadaptation in other zoonotic viruses.

show abstract

Effects of Transmission Bottlenecks on the Diversity of Influenza A Virus

Cited by 20 publications

References 73 publications

Within-Host Diversity of SARS-CoV-2 in COVID-19 Patients With Variable Disease Severities

Within-Host Diversity of SARS-CoV-2 in COVID-19 Patients With Variable Disease Severities

Genomic Diversity of Severe Acute Respiratory Syndrome–Coronavirus 2 in Patients With Coronavirus Disease 2019

Quantifying within-host diversity of H5N1 influenza viruses in humans and poultry in Cambodia

Contact Info

Product

Resources

About