Understanding the complex evolution of rapidly mutating viruses with deep sequencing: Beyond the analysis of viral diversity

Leung, Preston; Eltahla, Auda A.; Lloyd, Andrew R.; Bull, Rowena A.; Luciani, Fabio

doi:10.1016/j.virusres.2016.10.014

Cited by 23 publications

(12 citation statements)

References 113 publications

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“…Deep sequencing has recently become a powerful tool to analyze influenza virus genetic diversity and monitor adaptive mutations in hosts (49). In our study, we did not observe the emergence of variants with any other known mammalian adaptation markers, such as mutations in the HA to enhance binding for human-like receptors, except the increased dominance of the LPAI HK/4553 variant with PB2-K627.…”

Section: Discussioncontrasting

confidence: 54%

Risk Assessment of Fifth-Wave H7N9 Influenza A Viruses in Mammalian Models

Sun

Belser

Pappas

et al. 2019

J Virol

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The fifth wave of the H7N9 influenza epidemic in China was distinguished by a sudden increase in human infections, an extended geographic distribution, and the emergence of highly pathogenic avian influenza (HPAI) viruses. Genetically, some H7N9 viruses from the fifth wave have acquired novel amino acid changes at positions involved in mammalian adaptation, antigenicity, and hemagglutinin cleavability. Here, several human low-pathogenic avian influenza (LPAI) and HPAI H7N9 virus isolates from the fifth epidemic wave were assessed for their pathogenicity and transmissibility in mammalian models, as well as their ability to replicate in human airway epithelial cells. We found that an LPAI virus exhibited a similar capacity to replicate and cause disease in two animal species as viruses from previous waves. In contrast, HPAI H7N9 viruses possessed enhanced virulence, causing greater lethargy and mortality, with an extended tropism for brain tissues in both ferret and mouse models. These HPAI viruses also showed signs of adaptation to mammalian hosts by acquiring the ability to fuse at a lower pH threshold than other H7N9 viruses. All of the fifth-wave H7N9 viruses were able to transmit among cohoused ferrets but exhibited a limited capacity to transmit by respiratory droplets, and deep sequencing analysis revealed that the H7N9 viruses sampled after transmission showed a reduced amount of minor variants. Taken together, we conclude that the fifth-wave HPAI H7N9 viruses have gained the ability to cause enhanced disease in mammalian models and with further adaptation may acquire the ability to cause an H7N9 pandemic. IMPORTANCE The potential pandemic risk posed by avian influenza H7N9 viruses was heightened during the fifth epidemic wave in China due to the sudden increase in the number of human infections and the emergence of antigenically distinct LPAI and HPAI H7N9 viruses. In this study, a group of fifth-wave HPAI and LPAI viruses was evaluated for its ability to infect, cause disease, and transmit in small-animal models. The ability of HPAI H7N9 viruses to cause more severe disease and to replicate in brain tissues in animal models as well as their ability to fuse at a lower pH threshold than LPAI H7N9 viruses suggests that the fifth-wave H7N9 viruses have evolved to acquire novel traits with the potential to pose a higher risk to humans. Although the fifth-wave H7N9 viruses have not yet gained the ability to transmit efficiently by air, continuous surveillance and risk assessment remain essential parts of our pandemic preparedness efforts.

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Section: Discussioncontrasting

confidence: 54%

Risk Assessment of Fifth-Wave H7N9 Influenza A Viruses in Mammalian Models

Sun

Belser

Pappas

et al. 2019

J Virol

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“…As a high-throughput sequencing technology, viral metagenomics has been shown to be a powerful tool for identifying large numbers of known and novel viruses, and for investigating the viromes associated with complex disease syndromes 15 , 16 . Metagenomic sequencing has also been used to discover and characterize the viruses associated with respiratory diseases in humans, dairy and feedlot cattle 17 – 19 .…”

Section: Introductionmentioning

confidence: 99%

Viral communities associated with porcine respiratory disease complex in intensive commercial farms in Sichuan province, China

Qin

Ruan

Yue

et al. 2018

Sci Rep

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Porcine respiratory disease complex (PRDC), a common piglet disease, causes substantive economic losses in pig farming. To investigate the viral diversity associated with PRDC, the viral communities in serum and nasal swabs from 26 PRDC-affected piglets were investigated using metagenomics. By deep sequencing and de novo assembly, 17 viruses were identified in two pooled libraries (16 viruses from serum, nine from nasal swabs). Porcine circovirus (PCV)-2, porcine reproductive and respiratory syndrome virus (PRRSV) and pseudorabies virus, all commonly associated with PRDC, were identified in the two pooled samples by metagenomics, but most viruses comprised small linear and circular DNAs (e.g. parvoviruses, bocaviruses and circoviruses). PCR was used to compare the detection rates of each virus in the serum samples from 36 PRDC-affected piglets versus 38 location-matched clinically healthy controls. The average virus category per sample was 6.81 for the PRDC-affected piglets and 4.09 for the controls. Single or co-infections with PCV-2 or PRRSV had very high detection rates in the PRDC-affected piglets. Interestingly, porcine parvovirus (PPV)-2, PPV-3, PPV-6 and torque teno sus virus 1a were significantly associated with PRDC. These results illustrate the complexity of viral communities in the PRDC-affected piglets and highlight the candidate viruses associated with it.

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“…1 As technologies have evolved, the emergence of next-generation sequencing (NGS), which drastically reduced the cost per base to generate sequence data for complete viral genomes, has allowed scientists to apply viral sequencing on a grander scale. 2 Genomic sequencing is ideal for elucidating viral transmission pathways, characterizing emerging viruses, and locating genomic regions which are functionally important for evading the host immune system or antivirals. 3…”

Section: Introductionmentioning

confidence: 99%

The effect of variant interference on de novo assembly for viral deep sequencing

Castro

Marine

Ramos

et al. 2019

Preprint

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Viruses have high mutation rates and generally exist as a mixture of variants in biological samples. Next-generation sequencing (NGS) approach has surpassed Sanger for generating long viral sequences, yet how variants affect NGS de novo assembly remains largely unexplored. Our results from >15,000 simulated experiments showed that presence of variants can turn an assembly of one genome into tens to thousands of contigs. This “variant interference” (VI) is highly consistent and reproducible by ten most used de novo assemblers, and occurs independent of genome length, read length, and GC content. The main driver of VI is pairwise identities between viral variants. These findings were further supported by in silico simulations, where selective removal of minor variant reads from clinical datasets allow the “rescue” of full viral genomes from fragmented contigs. These results call for careful interpretation of contigs and contig numbers from de novo assembly in viral deep sequencing.

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Understanding the complex evolution of rapidly mutating viruses with deep sequencing: Beyond the analysis of viral diversity

Cited by 23 publications

References 113 publications

Risk Assessment of Fifth-Wave H7N9 Influenza A Viruses in Mammalian Models

Risk Assessment of Fifth-Wave H7N9 Influenza A Viruses in Mammalian Models

Viral communities associated with porcine respiratory disease complex in intensive commercial farms in Sichuan province, China

The effect of variant interference on de novo assembly for viral deep sequencing

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