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

Viruses ◽  
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.

scholarly journals Avian influenza A viruses reassort and diversify differently in mallards and mammals

2021 ◽  
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

AbstractReassortment 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 IAV 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.

scholarly journals Obatoclax, Saliphenylhalamide, and Gemcitabine Inhibit Influenza A Virus Infection

2012 ◽  
Vol 287 (42) ◽  
pp. 35324-35332 ◽  
Author(s):  
Oxana V. Denisova ◽  
Laura Kakkola ◽  
Lin Feng ◽  
Jakob Stenman ◽  
Ashwini Nagaraj ◽  
...  
Keyword(s):  
Influenza A ◽  
Treatment Options ◽  
Antiviral Agents ◽  
Cell Type ◽  
Influenza A Viruses ◽  
Novel Host ◽  
Chemical Screen ◽  
Species Specific ◽  
Host Target ◽  
Transcription And Replication

Influenza A viruses (IAVs) infect humans and cause significant morbidity and mortality. Different treatment options have been developed; however, these were insufficient during recent IAV outbreaks. Here, we conducted a targeted chemical screen in human nonmalignant cells to validate known and search for novel host-directed antivirals. The screen validated saliphenylhalamide (SaliPhe) and identified two novel anti-IAV agents, obatoclax and gemcitabine. Further experiments demonstrated that Mcl-1 (target of obatoclax) provides a novel host target for IAV treatment. Moreover, we showed that obatoclax and SaliPhe inhibited IAV uptake and gemcitabine suppressed viral RNA transcription and replication. These compounds possess broad spectrum antiviral activity, although their antiviral efficacies were virus-, cell type-, and species-specific. Altogether, our results suggest that phase II obatoclax, investigational SaliPhe, and FDA/EMEA-approved gemcitabine represent potent antiviral agents.

scholarly journals PB2 Residue 271 Plays a Key Role in Enhanced Polymerase Activity of Influenza A Viruses in Mammalian Host Cells

2010 ◽  
Vol 84 (9) ◽  
pp. 4395-4406 ◽  
Author(s):  
Kendra A. Bussey ◽  
Tatiana L. Bousse ◽  
Emily A. Desmet ◽  
Baek Kim ◽  
Toru Takimoto
Keyword(s):  
Mammalian Cells ◽  
Influenza A ◽  
Virus Titer ◽  
Polymerase Activity ◽  
Influenza Viruses ◽  
Host Cells ◽  
Mammalian Host ◽  
Influenza A Viruses ◽  
H5n1 Influenza ◽  
Avian Viruses

ABSTRACT The direct infection of humans with highly pathogenic avian H5N1 influenza viruses has suggested viral mutation as one mechanism for the emergence of novel human influenza A viruses. Although the polymerase complex is known to be a key component in host adaptation, mutations that enhance the polymerase activity of avian viruses in mammalian hosts are not fully characterized. The genomic comparison of influenza A virus isolates has identified highly conserved residues in influenza proteins that are specific to either human or avian viruses, including 10 residues in PB2. We characterized the activity of avian polymerase complexes containing avian-to-human mutations at these conserved PB2 residues and found that, in addition to the E627K mutation, the PB2 mutation T271A enhances polymerase activity in human cells. We confirmed the effects of the T271A mutation using recombinant WSN viruses containing avian NP and polymerase genes with wild-type (WT) or mutant PB2. The 271A virus showed enhanced growth compared to that of the WT in mammalian cells in vitro. The 271A mutant did not increase viral pathogenicity significantly in mice compared to that of the 627K mutant, but it did enhance the lung virus titer. Also, cell infiltration was more evident in lungs of 271A-infected mice than in those of the WT. Interestingly, the avian-derived PB2 of the 2009 pandemic H1N1 influenza virus has 271A. The characterization of the polymerase activity of A/California/04/2009 (H1N1) and corresponding PB2 mutants indicates that the high polymerase activity of the pandemic strain in mammalian cells is, in part, dependent on 271A. Our results clearly indicate the contribution of PB2 amino acid 271 to enhanced polymerase activity and viral growth in mammalian hosts.

scholarly journals Resurrected ancestral influenza A viruses recapitulate the avian-to-mammalian adaptation of European avian-like swine influenza virus

2021 ◽  
Author(s):  
Wen Su ◽  
Rhodri Harfoot ◽  
Yvonne Su ◽  
Jennifer DeBeauchamp ◽  
Udayan Joseph ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Influenza A ◽  
Swine Influenza Virus ◽  
Swine Influenza ◽  
Polymerase Activity ◽  
Influenza Viruses ◽  
Mammalian Host ◽  
Influenza A Viruses ◽  
Sequence Reconstruction

Abstract The emergence of a pandemic influenza virus may be better anticipated if we better understand the evolutionary steps taken by avian influenza viruses as they adapt to mammals. We used ancestral sequence reconstruction to resurrect viruses representing initial adaptive stages of the European avian-like H1N1 virus as it transitioned from avian to swine hosts. We demonstrate that efficient transmissibility in pigs was gained through stepwise adaptation after 1983. These time-dependent adaptations resulted in changes in hemagglutinin receptor binding specificity and increased viral polymerase activity. An NP-R351K mutation under strong positive selection increased the transmissibility of a reconstructed virus. The stepwise-adaptation of a wholly avian influenza virus to a mammalian host suggests a window where targeted intervention may have highest impact. Successful intervention will, however, require strategic coordination of surveillance and risk assessment activities to identify these adapting viruses and guide pandemic preparedness resources.

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

2018 ◽  
Vol 5 (3) ◽  
pp. 76 ◽  
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.

scholarly journals Specificity of the helper T cell for the cytolytic T lymphocyte response to influenza viruses

1981 ◽  
Vol 154 (2) ◽  
pp. 541-546 ◽  
Author(s):  
CS Reiss ◽  
SJ Burakoff
Keyword(s):  
T Cells ◽  
T Lymphocyte ◽  
Influenza A ◽  
Model System ◽  
Influenza Viruses ◽  
Helper T Cells ◽  
Cell Populations ◽  
Influenza A Viruses ◽  
Lymphocyte Response ◽  
Cytolytic T Lymphocyte

We have described a model system in which helper T cells are required to mount a primary antiviral cytolytic T lymphocyte response. The radioresistant helper cell can be found in the spleens of mice that have been immunized subcutaneously with influenza viruses 6-8 d previously. These helper cells appear to be type specific but cross-reactive among the subtypes of influenza A viruses. The phenotypes of the interacting cell populations were determined.

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

2019 ◽  
Author(s):  
Raquel Muñoz-Moreno ◽  
Carles Martínez-Romero ◽  
Daniel Blanco-Melo ◽  
Christian V. Forst ◽  
Raffael Nachbagauer ◽  
...  
Keyword(s):  
Host Species ◽  
Influenza A ◽  
Fitness Landscapes ◽  
Viral Fitness ◽  
Influenza A Viruses ◽  
Ns1 Gene

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

2019 ◽  
Vol 263 ◽  
pp. 34-46 ◽  
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

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

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.

scholarly journals Diversity and Reassortment Rate of Influenza A Viruses in Wild Ducks and Gulls

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1010
Author(s):  
Yulia Postnikova ◽  
Anastasia Treshchalina ◽  
Elizaveta Boravleva ◽  
Alexandra Gambaryan ◽  
Aydar Ishmukhametov ◽  
...  
Keyword(s):  
Influenza A ◽  
Phylogenetic Trees ◽  
Point Mutations ◽  
Viral Gene ◽  
Viral Diversity ◽  
Influenza A Viruses ◽  
Significant Difference ◽  
Complete Genomes ◽  
Gene Reassortment ◽  
Wild Mallard

Influenza A viruses (IAVs) evolve via point mutations and reassortment of viral gene segments. The patterns of reassortment in different host species differ considerably. We investigated the genetic diversity of IAVs in wild ducks and compared it with the viral diversity in gulls. The complete genomes of 38 IAVs of H1N1, H1N2, H3N1, H3N2, H3N6, H3N8, H4N6, H5N3, H6N2, H11N6, and H11N9 subtypes isolated from wild mallard ducks and gulls resting in a city pond in Moscow, Russia were sequenced. The analysis of phylogenetic trees showed that stable viral genotypes do not persist from year to year in ducks owing to frequent gene reassortment. For comparison, similar analyses were carried out using sequences of IAVs isolated in the same period from ducks and gulls in The Netherlands. Our results revealed a significant difference in diversity and rates of reassortment of IAVs in ducks and gulls.

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