Viral Fitness Landscapes in Diverse Host Species Reveal Multiple Evolutionary Lines for the NS1 Gene of Influenza A Viruses

ABSTRACT Wild-type (WT) influenza A/PR/8/34 virus and its variant lacking the NS1 gene (delNS1) have been compared for their ability to mediate apoptosis in cultured cells and chicken embryos. Cell morphology, fragmentation of chromatin DNA, and caspase-dependent cleavage of the viral NP protein have been used as markers for apoptosis. Another marker was caspase cleavage of the viral M2 protein, which was also found to occur in an apoptosis-specific manner. In interferon (IFN)-competent host systems, such as MDCK cells, chicken fibroblasts, and 7-day-old chicken embryos, delNS1 virus induced apoptosis more rapidly and more efficiently than WT virus. As a consequence, delNS1 virus was also more lethal for chicken embryos than WT virus. In IFN-deficient Vero cells, however, apoptosis was delayed and developed with similar intensity after infection with both viruses. Taken together, these data indicate that the IFN antagonistic NS1 protein of influenza A viruses has IFN-dependent antiapoptotic potential.

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Effect of the H275Y neuraminidase mutation on viral fitness of oseltamivir-resistant pandemic 2009 and seasonal H1N1 influenza A viruses

10.5353/th_b4961755 ◽

2012 ◽

Author(s):

Dik-yan, Diana Wong

Keyword(s):

Influenza A ◽

H1n1 Influenza ◽

Viral Fitness ◽

Influenza A Viruses

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Trade-offs between and within scales: environmental persistence and within-host fitness of avian influenza viruses

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2013.3051 ◽

2014 ◽

Vol 281 (1787) ◽

pp. 20133051 ◽

Cited By ~ 22

Author(s):

Andreas Handel ◽

Camille Lebarbenchon ◽

David Stallknecht ◽

Pejman Rohani

Keyword(s):

Avian Influenza ◽

Influenza A ◽

Influenza Viruses ◽

Viral Fitness ◽

Ecological Niches ◽

Influenza A Viruses ◽

Temperature Dependent ◽

Environmental Persistence ◽

Trade Off ◽

Trade Offs

Trade-offs between different components of a pathogen's replication and transmission cycle are thought to be common. A number of studies have identified trade-offs that emerge across scales, reflecting the tension between strategies that optimize within-host proliferation and large-scale population spread. Most of these studies are theoretical in nature, with direct experimental tests of such cross-scale trade-offs still rare. Here, we report an analysis of avian influenza A viruses across scales, focusing on the phenotype of temperature-dependent viral persistence. Taking advantage of a unique dataset that reports both environmental virus decay rates and strain-specific viral kinetics from duck challenge experiments, we show that the temperature-dependent environmental decay rate of a strain does not impact within-host virus load. Hence, for this phenotype, the scales of within-host infection dynamics and between-host environmental persistence do not seem to interact: viral fitness may be optimized on each scale without cross-scale trade-offs. Instead, we confirm the existence of a temperature-dependent persistence trade-off on a single scale, with some strains favouring environmental persistence in water at low temperatures while others reduce sensitivity to increasing temperatures. We show that this temperature-dependent trade-off is a robust phenomenon and does not depend on the details of data analysis. Our findings suggest that viruses might employ different environmental persistence strategies, which facilitates the coexistence of diverse strains in ecological niches. We conclude that a better understanding of the transmission and evolutionary dynamics of influenza A viruses probably requires empirical information regarding both within-host dynamics and environmental traits, integrated within a combined ecological and within-host framework.

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The evolutionary dynamics of influenza A virus adaptation to mammalian hosts

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2012.0382 ◽

2013 ◽

Vol 368 (1614) ◽

pp. 20120382 ◽

Cited By ~ 27

Author(s):

S. Bhatt ◽

T. T. Lam ◽

S. J. Lycett ◽

A. J. Leigh Brown ◽

T. A. Bowden ◽

...

Keyword(s):

Avian Influenza ◽

Adaptive Evolution ◽

Influenza A ◽

Evolutionary Dynamics ◽

Adaptive Dynamics ◽

Swine Influenza ◽

Influenza Viruses ◽

Viral Fitness ◽

Influenza A Viruses ◽

Entire Genome

Few questions on infectious disease are more important than understanding how and why avian influenza A viruses successfully emerge in mammalian populations, yet little is known about the rate and nature of the virus’ genetic adaptation in new hosts. Here, we measure, for the first time, the genomic rate of adaptive evolution of swine influenza viruses (SwIV) that originated in birds. By using a curated dataset of more than 24 000 human and swine influenza gene sequences, including 41 newly characterized genomes, we reconstructed the adaptive dynamics of three major SwIV lineages (Eurasian, EA; classical swine, CS; triple reassortant, TR). We found that, following the transfer of the EA lineage from birds to swine in the late 1970s, EA virus genes have undergone substantially faster adaptive evolution than those of the CS lineage, which had circulated among swine for decades. Further, the adaptation rates of the EA lineage antigenic haemagglutinin and neuraminidase genes were unexpectedly high and similar to those observed in human influenza A. We show that the successful establishment of avian influenza viruses in swine is associated with raised adaptive evolution across the entire genome for many years after zoonosis, reflecting the contribution of multiple mutations to the coordinated optimization of viral fitness in a new environment. This dynamics is replicated independently in the polymerase genes of the TR lineage, which established in swine following separate transmission from non-swine hosts.

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Analysis of the Variability in the Non-Coding Regions of Influenza A Viruses

Veterinary Sciences ◽

10.3390/vetsci5030076 ◽

2018 ◽

Vol 5 (3) ◽

pp. 76 ◽

Cited By ~ 1

Author(s):

Jessica Benkaroun ◽

Gregory Robertson ◽

Hugh Whitney ◽

Andrew Lang

Keyword(s):

Influenza Virus ◽

Host Species ◽

Influenza A ◽

Wild Bird ◽

Coding Region ◽

Influenza A Viruses ◽

Protein Coding ◽

Coding Regions ◽

Negative Sense ◽

Specific Sequences

The genomes of influenza A viruses (IAVs) comprise eight negative-sense single-stranded RNA segments. In addition to the protein-coding region, each segment possesses 5′ and 3′ non-coding regions (NCR) that are important for transcription, replication and packaging. The NCRs contain both conserved and segment-specific sequences, and the impacts of variability in the NCRs are not completely understood. Full NCRs have been determined from some viruses, but a detailed analysis of potential variability in these regions among viruses from different host groups and locations has not been performed. To evaluate the degree of conservation in NCRs among different viruses, we sequenced the NCRs of IAVs isolated from different wild bird host groups (ducks, gulls and seabirds). We then extended our study to include NCRs available from the National Center for Biotechnology Information (NCBI) Influenza Virus Database, which allowed us to analyze a wider variety of host species and more HA and NA subtypes. We found that the amount of variability within the NCRs varies among segments, with the greatest variation found in the HA and NA and the least in the M and NS segments. Overall, variability in NCR sequences was correlated with the coding region phylogeny, suggesting vertical coevolution of the (coding sequence) CDS and NCR regions.

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Integrated analysis of microRNA-mRNA expression in A549 cells infected with influenza A viruses (IAVs) from different host species

Virus Research ◽

10.1016/j.virusres.2018.12.016 ◽

2019 ◽

Vol 263 ◽

pp. 34-46 ◽

Cited By ~ 9

Author(s):

Jie Gao ◽

Lingxi Gao ◽

Rui Li ◽

Zhenping Lai ◽

Zengfeng Zhang ◽

...

Keyword(s):

Mrna Expression ◽

Host Species ◽

Influenza A ◽

A549 Cells ◽

Integrated Analysis ◽

Influenza A Viruses

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A30 Avian influenza viruses in wild birds: Virus evolution in a multi-host ecosystem

Virus Evolution ◽

10.1093/ve/vez002.029 ◽

2019 ◽

Vol 5 (Supplement_1) ◽

Author(s):

Divya Venkatesh ◽

Marjolein J Poen ◽

Theo M Bestebroer ◽

Rachel D Scheuer ◽

Oanh Vuong ◽

...

Keyword(s):

Avian Influenza ◽

Host Species ◽

Influenza A ◽

Phylogenetic Trees ◽

Influenza Viruses ◽

Influenza A Viruses ◽

East African ◽

Bird Populations ◽

Under Sampling ◽

The Republic

Abstract Wild ducks and gulls are the major reservoirs for avian influenza A viruses (AIVs). The mechanisms that drive AIV evolution are complex at sites where various duck and gull species from multiple flyways breed, winter, or stage. The Republic of Georgia is located at the intersection of three migratory flyways: the Central Asian Flyway, East Asian/East African Flyway, and Black Sea/Mediterranean Flyway. For six consecutive years (2010–6), we collected AIV samples from various duck and gull species that breed, migrate, and overwinter in Georgia. We found substantial subtype diversity of viruses that varied in prevalence from year to year. Low pathogenic (LP)AIV subtypes included H1N1, H2N3, H2N5, H2N7, H3N8, H4N2, H6N2, H7N3, H7N7, H9N1, H9N3, H10N4, H10N7, H11N1, H13N2, H13N6, H13N8, and H16N3, plus two H5N5 and H5N8 highly pathogenic (HP)AIVs belonging to clade 2.3.4.4. Whole-genome phylogenetic trees showed significant host species lineage restriction for nearly all gene segments and significant differences for LPAIVs among different host species in observed reassortment rates, as defined by quantification of phylogenetic incongruence, and in nucleotide diversity. Hemagglutinin clade 2.3.4.4 H5N8 viruses, circulated in Eurasia during 2014–5 did not reassort, but analysis after its subsequent dissemination during 2016–7 revealed reassortment in all gene segments except NP and NS. Some virus lineages appeared to be unrelated to AIVs in wild bird populations in other regions with maintenance of local AIV viruses in Georgia, whereas other lineages showed considerable genetic inter-relationship with viruses circulating in other parts of Eurasia and Africa, despite relative under-sampling in the area.

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Influenza A Viruses with Deletions in the NS1 Gene—a Rational Approach to Develop Oncolytic Viruses

Viral Therapy of Human Cancers ◽

10.1201/b14180-9 ◽

2004 ◽

pp. 591-612

Keyword(s):

Influenza A ◽

Oncolytic Viruses ◽

Rational Approach ◽

Influenza A Viruses ◽

Ns1 Gene

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Avian Influenza A Viruses Reassort and Diversify Differently in Mallards and Mammals

Viruses ◽

10.3390/v13030509 ◽

2021 ◽

Vol 13 (3) ◽

pp. 509

Author(s):

Ketaki Ganti ◽

Anish Bagga ◽

Juliana DaSilva ◽

Samuel S. Shepard ◽

John R. Barnes ◽

...

Keyword(s):

Linkage Disequilibrium ◽

Host Species ◽

Guinea Pigs ◽

Influenza A ◽

Model System ◽

Mammalian Host ◽

Viral Diversity ◽

Influenza A Viruses ◽

Longitudinal Patterns ◽

Novel Host

Reassortment among co-infecting influenza A viruses (IAVs) is an important source of viral diversity and can facilitate expansion into novel host species. Indeed, reassortment played a key role in the evolution of the last three pandemic IAVs. Observed patterns of reassortment within a coinfected host are likely to be shaped by several factors, including viral load, the extent of viral mixing within the host and the stringency of selection. These factors in turn are expected to vary among the diverse host species that IAV infects. To investigate host differences in IAV reassortment, here we examined reassortment of two distinct avian IAVs within their natural host (mallards) and a mammalian model system (guinea pigs). Animals were co-inoculated with A/wildbird/California/187718-36/2008 (H3N8) and A/mallard/Colorado/P66F1-5/2008 (H4N6) viruses. Longitudinal samples were collected from the cloaca of mallards or the nasal tract of guinea pigs and viral genetic exchange was monitored by genotyping clonal isolates from these samples. Relative to those in guinea pigs, viral populations in mallards showed higher frequencies of reassortant genotypes and were characterized by higher genotype richness and diversity. In line with these observations, analysis of pairwise segment combinations revealed lower linkage disequilibrium in mallards as compared to guinea pigs. No clear longitudinal patterns in richness, diversity or linkage disequilibrium were present in either host. Our results reveal mallards to be a highly permissive host for IAV reassortment and suggest that reduced viral mixing limits avian IAV reassortment in a mammalian host.

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