Human host factors required for influenza virus replication

König, Renate; Stertz, Silke; Zhou, Yingyao; Inoue, Atsushi; Hoffmann, Hans-Heinrich; Bhattacharyya, Suchita; Alamares, Judith G.; Tscherne, Donna M.; Ortigoza, Mila B.; Liang, Yuhong; Gao, Qinshan; Andrews, Shane E.; Bandyopadhyay, Sourav; Jesus, Paul D. De; Tu, Buu P.; Pache, Lars; Shih, Crystal; Orth, Anthony P.; Bonamy, Ghislain M. C.; Miraglia, Loren; Ideker, Trey; García‐Sastre, Adolfo; Young, John A. T.; Palese, Peter; Shaw, Megan L.; Chanda, Sumit K.

doi:10.1038/nature08699

Cited by 740 publications

(827 citation statements)

References 28 publications

(37 reference statements)

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“…Multiple siRNA screens for influenza virus, an NS RNA virus that replicates in the nucleus, have identified COPI, but not COPII, as required for infection (11,12,24). Although COPI is required for influenza as well as VSV G-mediated virus entry (12), our results for VSV are in contrast to these studies.…”

Section: Discussioncontrasting

confidence: 82%

“…The advent of siRNA technology and the availability of genome-wide siRNA libraries have been useful in identifying host factors required for influenza virus, an NS RNA virus, and several positive-strand RNA viruses, as well as HIV (10)(11)(12)(13)(14)(15)(16)(17)(18)(19). The lack of similar studies with other NS RNA viruses has limited the understanding of the role of host cell factors in replication of these viruses.…”

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confidence: 99%

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RNAi screening reveals requirement for host cell secretory pathway in infection by diverse families of negative-strand RNA viruses

Panda

Das

Dinh

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Negative-strand (NS) RNA viruses comprise many pathogens that cause serious diseases in humans and animals. Despite their clinical importance, little is known about the host factors required for their infection. Using vesicular stomatitis virus (VSV), a prototypic NS RNA virus in the family Rhabdoviridae, we conducted a human genomewide siRNA screen and identified 72 host genes required for viral infection. Many of these identified genes were also required for infection by two other NS RNA viruses, the lymphocytic choriomeningitis virus of the Arenaviridae family and human parainfluenza virus type 3 of the Paramyxoviridae family. Genes affecting different stages of VSV infection, such as entry/uncoating, gene expression, and assembly/release, were identified. Depletion of the proteins of the coatomer complex I or its upstream effectors ARF1 or GBF1 led to detection of reduced levels of VSV RNA. Coatomer complex I was also required for infection of lymphocytic choriomeningitis virus and human parainfluenza virus type 3. These results highlight the evolutionarily conserved requirements for gene expression of diverse families of NS RNA viruses and demonstrate the involvement of host cell secretory pathway in the process.RNA interference | transcription and replication | host cell factors for virus infection

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Section: Discussioncontrasting

confidence: 82%

mentioning

confidence: 99%

RNAi screening reveals requirement for host cell secretory pathway in infection by diverse families of negative-strand RNA viruses

Panda

Das

Dinh

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…Genomewide RNA interference screening has identified the cognate receptor for KGF, FGFR2, as one of 23 proteins required for viral entry and the PI3K/Akt/mTOR, MAPK, and IP-3 PKC signaling pathways as most essential for early-stage IAV replication (42). There is also evidence that IAV uses molecular mimicry and other mechanisms to activate cellular signaling pathways to augment its own internalization and proliferation.…”

Section: Discussionmentioning

confidence: 99%

Mitogenic stimulation accelerates influenza-induced mortality by increasing susceptibility of alveolar type II cells to infection

Nikolaidis

Noel²,

Pitstick

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Development of pneumonia is the most lethal consequence of influenza, increasing mortality more than 50-fold compared with uncomplicated infection. The spread of viral infection from conducting airways to the alveolar epithelium is therefore a pivotal event in influenza pathogenesis. We found that mitogenic stimulation with keratinocyte growth factor (KGF) markedly accelerated mortality after infectious challenge with influenza A virus (IAV). Coadministration of KGF with IAV markedly accelerated the spread of viral infection from the airways to alveoli compared with challenge with IAV alone, based on spatial and temporal analyses of viral nucleoprotein staining of lung tissue sections and dissociated lung cells. To better define the temporal relationship between KGF administration and susceptibility to IAV infection in vivo, we administered KGF 120, 48, 24, and 0 h before intrapulmonary IAV challenge and assessed the percentages of proliferating and IAV-infected, alveolar type II (AECII) cells in dispersed lung cell populations. Peak AECII infectivity coincided with the timing of KGF administration that also induced peak AECII proliferation. AECII from mice that were given intrapulmonary KGF before isolation and then infected with IAV ex vivo exhibited the same temporal pattern of proliferation and infectious susceptibility. KGF-induced increases in mortality, AECII proliferation, and enhanced IAV susceptibility were all reversed by pretreatment of the animals with the mTOR inhibitor rapamycin before mitogenic stimulation. Taken together, these data suggest mTOR signalingdependent, mitogenic conditioning of AECII is a determinant of host susceptibility to infection with IAV. viral pneumonia | influenza A | alveolar epithelial type II | mitogen | mTOR

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“…Intracellular Ca 2 þ has previously been implicated in IAV infection 48,49 , with Ca 2 þ having been thought to have a role in the late stage of infection. For instance, Ca 2 þ acting through calmodulin is required for the transcription and replication of IAV genes 48,49 , with inhibition of such Ca 2 þ action being expected to attenuate viral messenger RNA replication in the nucleus. Consistent with this notion, we found that BAPTA-AM treatment during the late stage of IAV infection inhibited the generation of progeny viruses, albeit less efficiently than that during the early stage.…”

Section: Discussionmentioning

confidence: 99%

A Ca2+-dependent signalling circuit regulates influenza A virus internalization and infection

et al. 2013

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Various viruses enter host cells via endocytosis, but the molecular mechanisms underlying the specific internalization pathways remain unclear. Here we show that influenza A viruses (IAVs) enter cells via redundant pathways of clathrin-mediated and clathrin-independent endocytosis, with intracellular Ca2+ having a central role in regulation of both pathways by activating a signalling axis comprising RhoA, Rho-kinase, phosphatidylinositol 4-phosphate 5-kinase (PIP5K) and phospholipase C (PLC). IAV infection induces oscillations in the cytosolic Ca2+ concentration of host cells, the prevention of which markedly attenuates virus internalization and infection. The small GTPase RhoA is found both to function downstream of the virus-induced Ca2+ response and itself to induce Ca2+ oscillations in a manner dependent on Rho-kinase and subsequent PIP5K-PLC signalling. This signalling circuit regulates both clathrin-mediated and clathrin-independent endocytosis during virus infection and seems to constitute a key mechanism for regulation of IAV internalization and infection

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Human host factors required for influenza virus replication

Cited by 740 publications

References 28 publications

RNAi screening reveals requirement for host cell secretory pathway in infection by diverse families of negative-strand RNA viruses

RNAi screening reveals requirement for host cell secretory pathway in infection by diverse families of negative-strand RNA viruses

Mitogenic stimulation accelerates influenza-induced mortality by increasing susceptibility of alveolar type II cells to infection

A Ca2+-dependent signalling circuit regulates influenza A virus internalization and infection

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