Effects of hexose starvation and the role of sialic acid in influenza virus release

Griffin, Johanna A.; Basak, Sukla; Compans, Richard W.

doi:10.1016/0042-6822(83)90205-2

Cited by 70 publications

(39 citation statements)

References 27 publications

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“…Specifically, NA enzymatically cleaves sialic acid, the influenza host cell receptor, and facilitates the release of viral particles that allows them to infect additional cells (4 -6). Indeed, this role is supported by the observation that NA-defective virus or wild type viruses in the presence of NA inhibitors form aggregations on the apical surface of the cells (7)(8)(9). Furthermore, NA has been suggested to play additional roles in viral infection including mucus breakdown, which allows for increased viral diffusion throughout the respiratory tract during infection (10,11) and more recently has been shown to contribute to the entry and fusion of the influenza virus into host cells (12,13).…”

supporting

confidence: 49%

The Universal Epitope of Influenza A Viral Neuraminidase Fundamentally Contributes to Enzyme Activity and Viral Replication

Doyle

Jaentschke

Domselaar

et al. 2013

Journal of Biological Chemistry

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Background:The influenza viral neuraminidase has only one universally conserved peptide sequence with unknown function. Results: Sequence alterations in this region decrease substrate binding, enzymatic activity, protein stability, and viral growth. Conclusion:The universal epitope is indispensable for maximal enzymatic function and robust viral propagation. Significance: The universally conserved NA sequence is an attractive target for antiviral intervention and vaccine development.

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supporting

confidence: 49%

The Universal Epitope of Influenza A Viral Neuraminidase Fundamentally Contributes to Enzyme Activity and Viral Replication

Doyle

Jaentschke

Domselaar

et al. 2013

Journal of Biological Chemistry

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“…3). Under these conditions, DC are infected since NA is not required for infection, but virus is not released from the host cell surface (7,17). When zanamivir was added during the first 4 h of infection only, IL-4 was secreted by the responding allogeneic T cells (Fig.…”

Section: Discussionmentioning

confidence: 99%

Polarization of Allogeneic T-Cell Responses by Influenza Virus-Infected Dendritic Cells

Eichelberger

2000

J Virol

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The developing immune response in the lymph nodes of mice infected with influenza virus has both Th1-and Th2-type characteristics. Modulation of the interactions between antigen-presenting cells and T cells is one mechanism that may alter the quality of the immune response. We have previously shown that the ability of dendritic cells (DC) to stimulate the proliferation of alloreactive T cells is changed by influenza virus due to viral neuraminidase (NA) activity. Here we show that DC infected with influenza virus A/PR/8/34 (PR8) stimulate T cells to produce different types of cytokines in a dose-dependent manner. Optimal amounts of the Th1-type cytokines interleukin-2 (IL-2) and gamma interferon (IFN-␥) were produced from T cells stimulated by DC infected with low doses of PR8, while the Th2-type cytokines IL-4 and IL-10 were produced only in response to DC infected with high doses of PR8. IL-2 and IFN-␥ levels corresponded with T-cell proliferation and were dependent on the activity of viral NA on the DC surface. In contrast, IL-4 secretion required the treatment of T cells with NA. Since viral particles were released only from DC that are infected with high doses of PR8, our results suggest that viral NA on newly formed virus particles desialylates T-cell surface molecules to facilitate a Th2-type response. These results suggest that the activity of NA may contribute to the mixed Th-type response observed during influenza virus infection.The immune response to influenza virus has typical Th1-type characteristics, with production of interleukin-2 (IL-2), gamma interferon (IFN-␥), and cytotoxic T lymphocytes. However, cells that have Th2-type characteristics are also evident: in situ hybridization and enzyme-linked immunosorbent spotting analysis have demonstrated the presence of IL-4-, IL-5-, and IL-10-secreting cells in infected mice (2,3,26). The types of cytokines present during the initiation of an immune response are reflected by the isotypes of antibodies produced (30). The heterogeneity of influenza virus-specific antibody isotypes present in infected mice (20) may result from such mixed Th populations. It is interesting that isotype predominance depends on the replicative capacity of influenza virus and the site of immune induction (20). This suggests that the quantity of virus present in particular lymph nodes or the way in which the virus is presented at a particular site may direct the types of cytokines secreted by Th cells.We therefore proposed that the quantity and quality of the T-cell response are altered by the infection of antigen-presenting cells with influenza virus. We have demonstrated that alloreactive T-cell proliferation stimulated by dendritic cells (DC), the primary antigen-presenting cell type, is altered by influenza virus in a dose-dependent manner (24). Enhanced proliferation is a result of desialylation of DC surface molecules by viral neuraminidase (NA) (23), one of the major surface glycoproteins that are required for the release of newly formed virions from the host cell (1, 1...

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“…In several experiments performed much later, MDCK (Madin-Darby canine kidney) or EAC (Ehrlich ascites carcinoma) cells were briefly treated with Vibrio cholerae sialidase and then infected with influenza virus. Influenza virus infections were decreased by 90 to 100% as a result of the sialidase treatment (6,13,52). Micromonospora viridifaciens sialidase was also used to destroy cellular influenza virus receptors in cell culture assays (2).…”

Section: Influenza Caused By Infection With Influenza Virus a (Ifvmentioning

confidence: 99%

Sialidase Fusion Protein as a Novel Broad-Spectrum Inhibitor of Influenza Virus Infection

Malakhov¹,

Aschenbrenner²,

Smee

et al. 2006

Antimicrob Agents Chemother

213

214

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Influenza is a highly infectious disease characterized by recurrent annual epidemics and unpredictable major worldwide pandemics. Rapid spread of the highly pathogenic avian H5N1 strain and escalating human infections by the virus have set off the alarm for a global pandemic. To provide an urgently needed alternative treatment modality for influenza, we have generated a recombinant fusion protein composed of a sialidase catalytic domain derived from Actinomyces viscosus fused with a cell surface-anchoring sequence. The sialidase fusion protein is to be applied topically as an inhalant to remove the influenza viral receptors, sialic acids, from the airway epithelium. We demonstrate that a sialidase fusion construct, DAS181, effectively cleaves sialic acid receptors used by both human and avian influenza viruses. The treatment provides long-lasting effect and is nontoxic to the cells. DAS181 demonstrated potent antiviral and cell protective efficacies against a panel of laboratory strains and clinical isolates of IFV A and IFV B, with virus replication inhibition 50% effective concentrations in the range of 0.04 to 0.9 nM. Mouse and ferret studies confirmed significant in vivo efficacy of the sialidase fusion in both prophylactic and treatment modes.

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Effects of hexose starvation and the role of sialic acid in influenza virus release

Cited by 70 publications

References 27 publications

The Universal Epitope of Influenza A Viral Neuraminidase Fundamentally Contributes to Enzyme Activity and Viral Replication

The Universal Epitope of Influenza A Viral Neuraminidase Fundamentally Contributes to Enzyme Activity and Viral Replication

Polarization of Allogeneic T-Cell Responses by Influenza Virus-Infected Dendritic Cells

Sialidase Fusion Protein as a Novel Broad-Spectrum Inhibitor of Influenza Virus Infection

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