The influenza fingerprints: NS1 and M1 proteins contribute to specific host cell ultrastructure signatures upon infection by different influenza A viruses

Terrier, B.; Moulés, Vincent; Carron, Coralie; Cartet, Gaëlle; Frobert, Émilie; Yver, Matthieu; Traversier, Aurélien; Wolff, Thorsten; Riteau, Béatrice; Naffakh, Nadia; Lina, Bruno; Diaz, Jean‐Jacques; Rosa‐Calatrava, Manuel

doi:10.1016/j.virol.2012.05.019

Cited by 22 publications

(33 citation statements)

References 54 publications

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“…Nucleoli are known to disintegrate during virus infection, suggesting that NP nucleolar localization and binding to nucleolar components might be coordinated with other virus‐induced processes in nucleoli. NP by itself is not able to induce disruption of nucleoli though, as we could observe here and as it was also previously shown by electron microscopy (Terrier et al, ). Terrier et al .…”

Section: Discussionsupporting

confidence: 89%

Influenza A virus nucleoprotein targets subnuclear structures

Höfer

Jolmes

Haralampiev

et al. 2016

Cellular Microbiology

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The Influenza A virus nucleoprotein (NP) is the major protein component of the genomic viral ribonucleoprotein (vRNP) complexes, which are the replication- and transcription-competent units of Influenza viruses. Early during infection, NP mediates import of vRNPs into the host cell nucleus where viral replication and transcription take place; also newly synthesized NP molecules are targeted into the nucleus, enabling coreplicational assembly of progeny vRNPs. NP reportedly acts as regulatory factor during infection, and it is known to be involved in numerous interactions with host cell proteins. Yet, the NP-host cell interplay is still poorly understood. Here, we report that NP significantly interacts with the nuclear compartment and displays distinct affinities for different subnuclear structures. NP subnuclear behavior was studied by expression of fluorescent NP fusion proteins - including obligate monomeric NP - and site-specific fluorescence photoactivation measurements. We found that NP constructs accumulate in subnuclear domains frequently found adjacent to or overlapping with promyelocytic leukemia bodies and Cajal bodies. Targeting of NP to Cajal bodies could further be demonstrated in the context of virus infection. We hypothesize that by targeting functional nuclear organization, NP might either link viral replication to specific cellular machinery or interfere with host cell processes.

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Section: Discussionsupporting

confidence: 89%

Influenza A virus nucleoprotein targets subnuclear structures

Höfer

Jolmes

Haralampiev

et al. 2016

Cellular Microbiology

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“…The H5N1 strains A/Hong Kong/156/97 (HK/97) and A/Thailand/1(Kan-1)/2004 (Thai/04) were derived from lethally infected human patients, whereas A/chicken/Indonesia/R132/2004 (Ch/Ind), A/duck/Vietnam/TG24-O1/2005 (Duck/VN) and A/common buzzard/Berlin/1/2006 (Buzz/Bln) were of avian origin. Since we analyzed the contribution of the viral NS1 protein in the control of type I IFN induction, we also included a delNS1 deletion variant of the Pan/99 (H3N2) virus lacking the NS1 coding region in our study [44].…”

Section: Resultsmentioning

confidence: 99%

Highly Pathogenic H5N1 Influenza A Virus Strains Provoke Heterogeneous IFN-α/β Responses That Distinctively Affect Viral Propagation in Human Cells

2013

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The fatal transmissions of highly pathogenic avian influenza A viruses (IAV) of the H5N1 subtype to humans and high titer replication in the respiratory tract indicate that these pathogens can overcome the bird-to-human species barrier. While type I interferons (IFN-α/β) are well described to contribute to the species barrier of many zoonotic viruses, current data to the role of these antiviral cytokines during human H5N1 IAV infections is limited and contradictory. We hypothesized an important role for the IFN system in limiting productive infection of avian H5N1 strains in human cells. Hence, we examined IFN-α/β gene activation by different avian and human H5N1 isolates, if the IFN-α/β response restricts H5N1 growth and whether the different strains were equally capable to regulate the IFN-α/β system via their IFN-antagonistic NS1 proteins. Two human H5N1 isolates and a seasonal H3N2 strain propagated efficiently in human respiratory cells and induced little IFN-β, whereas three purely avian H5N1 strains were attenuated for replication and provoked higher IFN secretion. Replication of avian viruses was significantly enhanced on interferon-deficient cells, and exogenous IFN potently limited the growth of all strains in human cells. Moreover, IFN-α/β activation by all strains depended on retinoic acid-inducible gene I excluding principal differences in receptor activation between the different viruses. Interestingly, all H5N1 NS1 proteins suppressed IFN-α/β induction comparably well to the NS1 of seasonal IAV. Thus, our study shows that H5N1 strains are heterogeneous in their capacity to activate human cells in an NS1-independent manner. Our findings also suggest that H5N1 viruses need to acquire adaptive changes to circumvent strong IFN-α/β activation in human host cells. Since no single amino acid polymorphism could be associated with a respective high- or low induction phenotype we propose that the necessary adaptations to overcome the human IFN-α/β barrier involve mutations in multiple H5N1 genes.

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“…Such a nuclear localization is uncommon for RNA viruses and highlights that influenza virus can directly interfere with the host nuclear machineries and their components. Evidence for this is illustrated during infection by a major remodeling of host nuclear ultrastructures (3, 8) and by multiple functional interactions between IAV and host nuclear factors, an example being the 5′-cap snatching from host pre-mRNAs to viral ones (reviewed in reference 9). Interestingly, influenza viruses have developed various strategies to optimize the coding potential of their segmented genome.…”

Section: Introductionmentioning

confidence: 99%

Influenza Viruses and mRNA Splicing: Doing More with Less

Dubois

Terrier

Rosa‐Calatrava

2014

mBio

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129

132

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During their nuclear replication stage, influenza viruses hijack the host splicing machinery to process some of their RNA segments, the M and NS segments. In this review, we provide an overview of the current knowledge gathered on this interplay between influenza viruses and the cellular spliceosome, with a particular focus on influenza A viruses (IAV). These viruses have developed accurate regulation mechanisms to reassign the host spliceosome to alter host cellular expression and enable an optimal expression of specific spliced viral products throughout infection. Moreover, IAV segments undergoing splicing display high levels of similarity with human consensus splice sites and their viral transcripts show noteworthy secondary structures. Sequence alignments and consensus analyses, along with recently published studies, suggest both conservation and evolution of viral splice site sequences and structure for improved adaptation to the host. Altogether, these results emphasize the ability of IAV to be well adapted to the host’s splicing machinery, and further investigations may contribute to a better understanding of splicing regulation with regard to viral replication, host range, and pathogenesis.

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The influenza fingerprints: NS1 and M1 proteins contribute to specific host cell ultrastructure signatures upon infection by different influenza A viruses

Cited by 22 publications

References 54 publications

Influenza A virus nucleoprotein targets subnuclear structures

Influenza A virus nucleoprotein targets subnuclear structures

Highly Pathogenic H5N1 Influenza A Virus Strains Provoke Heterogeneous IFN-α/β Responses That Distinctively Affect Viral Propagation in Human Cells

Influenza Viruses and mRNA Splicing: Doing More with Less

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