Programmed Cell Death (Apoptosis) in Human Monocytes Infected by Influenza A Virus

Fesq, Heike; Bacher, Michael; Nain, Marianne; Gemsa, Diethard

doi:10.1016/s0171-2985(11)80292-5

Cited by 154 publications

(95 citation statements)

References 13 publications

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“…An induction of apoptosis by influenza viruses of various subtypes and strains has been observed in cultured cells (Fesq et al, 1994;Hinshaw et al, 1994;Hofmann et al, 1997;Takizawa et al, 1993) and in vivo (Mori et al, 1995). Although thought to impact viral replication and pathogenesis, the precise mechanisms and pathways of the observed phenomena are not fully understood.…”

Section: Discussionmentioning

confidence: 99%

“…The tumour necrosis factor (TNF) members, including the Fas ligand (FasL), TNF-a and TNF-related apoptosis-inducing ligand (TRAIL), and their receptors play key roles in the extrinsic apoptotic pathway in a variety of cell types. Influenza viruses induce apoptosis in the cells of various mammalian species (Fesq et al, 1994;Hinshaw et al, 1994;Hofmann et al, 1997;Morris et al, 1999Morris et al, , 2005Takizawa et al, 1993) and in chicken cells (Ito et al, 2002). Both intrinsic and extrinsic pathways can be involved in apoptosis, which presumably promotes infection and alters viral pathogenesis in the host (Brydon et al, 2005;Brydon et al, 2003;Hofmann et al, 1997;Lowy, 2003;Uiprasertkul et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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Differential regulation of antiviral and proinflammatory cytokines and suppression of Fas-mediated apoptosis by NS1 of H9N2 avian influenza virus in chicken macrophages

Xing

Cardona

Adams

et al. 2009

Journal of General Virology

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The NS1 protein is known to suppress immune responses in influenza virus-infected hosts. However, the role of NS1 in apoptosis in infected cells is disputed. In this study, through the use of a mutant A/pheasant/California/2373/1998 (H9N2) avian influenza virus (AIV) with a truncated NS1, we have demonstrated that a functional NS1 protein suppresses the induction of interferons in chicken macrophages. However, NS1 appeared to be irrelevant to the regulation of cytokines interleukin (IL)-1β and IL-6, indicating that distinct mechanisms may be employed in the regulation of antiviral and proinflammatory cytokines in chicken immune cells. Our study also showed that this H9N2 AIV induced apoptosis extrinsically through the Fas/Fas ligand (FasL)-mediated pathway. We found that NS1 suppressed the apoptotic process through suppression of the induction of FasL, but not tumour necrosis factor-α or TNF-related apoptosis-inducing ligand. Furthermore, our data indicated that the disruption of a potential binding site for the p85β subunit of phosphoinositide 3-kinase in the carboxyl terminus of NS1, while having no effect on the regulation of IFN induction, may contribute to the suppression of Fas/FasL-mediated apoptosis. Therefore, suppression of Fas/FasL-mediated apoptosis by NS1 is one of the critical mechanisms necessary to increase infectivity in AIV-infected chicken macrophages.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Differential regulation of antiviral and proinflammatory cytokines and suppression of Fas-mediated apoptosis by NS1 of H9N2 avian influenza virus in chicken macrophages

Xing

Cardona

Adams

et al. 2009

Journal of General Virology

View full text Add to dashboard Cite

show abstract

“…Influenza virus causes apoptotic death of cultured cell lines (Takizawa et al, 1993;Fesq et al, 1994;Hinshaw et al, 1994) as well as of tissues in infected animals (Mori et al, 1995). We previously showed that production of Fas (Peter et al, 1996;Nagata, 1997), also called APO-1 or CD95, increases at the transcription level in influenza virus-infected cells prior to their death (Takizawa et al, 1993.…”

Section: Introductionmentioning

confidence: 99%

Co-expression of Fas and Fas-ligand on the surface of influenza virus-infected cells

et al. 1998

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Influenza virus-infected cultured cells undergo apoptosis after an increment of Fas (APO-1/CD95) on the cell surface. By flow cytometry, cell surface Fas-ligand was detected in virusinfected cells with a time course similar to that of Fas. Moreover, Fas and Fas-ligand were co-expressed in those cells. The mode of induction, however, appeared to be distinct for the two proteins. Influenza virus infection induced the externalization of phosphatidylserine on the cell surface at the early stage of apoptosis, an event that has been observed in cells undergoing Fas-mediated apoptosis. In fact, apoptosis of the virus-infected cells was inhibited in the presence of an antagonistic anti-Fas-ligand monoclonal antibody. These results suggest that influenza virus infection causes augmented expression of both Fas and Fas-ligand and apoptosis is induced when the infected cells come into contact with each other.

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“…Influenza viruses are reported to induce apoptosis in numerous cell types, both in vivo (28,37,39) and in vitro (12,17,26,29,41,42,44,48,49). The virus induces apoptosis in infected cells as part of the mechanisms contributing to cellular and organ dysfunction (38,52).…”

mentioning

confidence: 99%

Avian Influenza Virus A/HK/483/97(H5N1) NS1 Protein Induces Apoptosis in Human Airway Epithelial Cells

Lam

Tang²,

Yeung³

et al. 2008

J Virol

108

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Avian H5N1 influenza virus causes a remarkably severe disease in humans, with an overall case fatality rate of greater than 50%. Human influenza A viruses induce apoptosis in infected cells, which can lead to organ dysfunction. To verify the role of H5N1-encoded NS1 in inducing apoptosis, the NS1 gene was cloned and expressed in human airway epithelial cells (NCI-H292 cells). The apoptotic events posttransfection were examined by a terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick-end-labeling assay, flow cytometric measurement of propidium iodide, annexin V staining, and Western blot analyses with antibodies specific for proapoptotic and antiapoptotic proteins. We demonstrated that the expression of H5N1 NS1 protein in NCI-H292 cells was sufficient to induce apoptotic cell death. Western blot analyses also showed that there was prominent cleavage of poly(ADP-ribose) polymerase and activation of caspase-3, caspase-7, and caspase-8 during the NS1-induced apoptosis. The results of caspase inhibitor assays further confirmed the involvement of caspase-dependent pathways in the NS1-induced apoptosis. Interestingly, the ability of H5N1 NS1 protein to induce apoptosis was much enhanced in cells pretreated with Fas ligand (the time posttransfection required to reach >30% apoptosis was reduced from 24 to 6 h). Furthermore, 24 h posttransfection, an increase in Fas ligand mRNA expression of about 5.6-fold was detected in cells transfected with H5N1 NS1. In conclusion, we demonstrated that the NS1 protein encoded by avian influenza A virus H5N1 induced apoptosis in human lung epithelial cells, mainly via the caspase-dependent pathway, which encourages further investigation into the potential for the NS1 protein to be a novel therapeutic target.

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Programmed Cell Death (Apoptosis) in Human Monocytes Infected by Influenza A Virus

Cited by 154 publications

References 13 publications

Differential regulation of antiviral and proinflammatory cytokines and suppression of Fas-mediated apoptosis by NS1 of H9N2 avian influenza virus in chicken macrophages

Differential regulation of antiviral and proinflammatory cytokines and suppression of Fas-mediated apoptosis by NS1 of H9N2 avian influenza virus in chicken macrophages

Co-expression of Fas and Fas-ligand on the surface of influenza virus-infected cells

Avian Influenza Virus A/HK/483/97(H5N1) NS1 Protein Induces Apoptosis in Human Airway Epithelial Cells

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