High yields of influenza A virus in Madin-Darby canine kidney cells are promoted by an insufficient interferon-induced antiviral state

Seitz, C.; Frensing, Timo; Höper, Dirk W.; Kochs, Georg; Reichl, Udo

doi:10.1099/vir.0.020370-0

Cited by 75 publications

(57 citation statements)

References 54 publications

(51 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results thus indicate that IFN induction may not be the only cause of limited delNS1 virus replication in MDCK cells. Several recent studies already suggest that IFN has a minor effect on influenza virus replication in MDCK cells because canine myxovirus resistance proteins lack anti-influenza activity (38) and secreted IFN is proteolytically degraded by trypsin, which is normally present during influenza virus production on MDCK cells (39). Furthermore, delNS1 virus titers could be increased by recombinant NS1 expression, without lowering IFN induction (46), indicating that IFN induction in MDCK may play a less important role than generally assumed.…”

Section: Discussionmentioning

confidence: 82%

Mutations in the M-Gene Segment Can Substantially Increase Replication Efficiency of NS1 Deletion Influenza A Virus in MDCK Cells

Wielink

Harmsen

Martens

et al. 2012

J Virol

View full text Add to dashboard Cite

bInfluenza viruses unable to express NS1 protein (delNS1) replicate poorly and induce large amounts of interferon (IFN). They are therefore considered candidate viruses for live-attenuated influenza vaccines. Their attenuated replication is generally assumed to result from the inability to counter the antiviral host response, as delNS1 viruses replicate efficiently in Vero cells, which lack IFN expression. In this study, delNS1 virus was parallel passaged on IFN-competent MDCK cells, which resulted in two strains that were able to replicate to high virus titers in MDCK cells due to adaptive mutations especially in the M-gene segment but also in the NP and NS gene segments. Most notable were clustered U-to-C mutations in the M segment of both strains and clustered A-to-G mutations in the NS segment of one strain, which presumably resulted from host cell-mediated RNA editing. The M segment mutations in both strains changed the ratio of M1 to M2 expression, probably by affecting splicing efficiency. In one virus, 2 amino acid substitutions in M1 additionally enhanced virus replication, possibly through changes in the M1 distribution between the nucleus and the cytoplasm. Both adapted viruses induced levels of IFN equal to that of the original delNS1 virus. These results show that the increased replication of the adapted viruses is not primarily due to altered IFN induction but rather is related to changes in M1 expression or localization. The mutations identified in this paper may be used to enhance delNS1 virus replication for vaccine production.

show abstract

Section: Discussionmentioning

confidence: 82%

Mutations in the M-Gene Segment Can Substantially Increase Replication Efficiency of NS1 Deletion Influenza A Virus in MDCK Cells

Wielink

Harmsen

Martens

et al. 2012

J Virol

View full text Add to dashboard Cite

show abstract

“…The latter assumption is also supported by experimental results for A/H1N1-NIBSC (see Section 5.8, page 78). As Seitz et al [2010] show, the level of IFN expression strongly depends on the specific influenza virus strain. They also demonstrate that, though there is no significant effect on the final virus yield of the specific virus strain, manipulation of the IFN expression in MDCK cells has an influence on the intermediate dynamics of influenza virus replication.…”

Section: Distribution Dynamicsmentioning

confidence: 96%

Population balance modeling of influenza virus replication in MDCK cells during vaccine production

Mueller

Schulze‐Horsel

Sidorenko

et al. 2008

Computer Aided Chemical Engineering

View full text Add to dashboard Cite

“…MDCK cells are widely used for the primary isolation of influenza viruses because of their high susceptibility to infection with various strains of the viruses (3,4,19). For MDCK cells infected with EIV A1 and A2, a weak signal of the PS translocation was observed, while more cells indicated the DNA fragmentation.…”

Section: Discussionmentioning

confidence: 99%

Induction of Apoptosis in MDCK, RK13, and Neuro-2A Cells Infected with Equine Influenza Virus

Kwasnik¹,

Rozek

Zmudzinski

2013

Bulletin of the Veterinary Institute in Pulawy

View full text Add to dashboard Cite

The purpose of the experiment was to compare apoptosis induced by equine influenza virus (EIV A1 and EIV A2) infection in MDCK, RK13, and NEURO-2A cell lines. Flow cytometry was used to observe two symptoms of apoptosis: phosphatidylserine translocation in plasmalemma (annexin V assay) and the fragmentation of DNA generated by endonuclease activity (TUNEL assayterminal deoxynucleotidyl transferase biotin-dUTP nick end labelling). The differences in the onset of apoptosis in the studied cells was observed. In MDCK cells infected with EIV A1 and A2, a weak signal of the phosphatidylserine translocation was observed but more cells showed the DNA fragmentation. An opposite effect was observed in case of RK 13 cells. NEURO-2A cells displayed a similar number of annexin V and TUNEL positive cells after the infection with EIV A2, while in case of EIV A1 infection, only the early symptoms of apoptosis were noted. Differences between both viral serotypes could originate from functioning of viral proteins responsible for induction or inhibition of apoptosis. The differences between cell types may result from the activation of cellular pro or anti-apoptotic mechanisms.

show abstract

High yields of influenza A virus in Madin-Darby canine kidney cells are promoted by an insufficient interferon-induced antiviral state

Cited by 75 publications

References 54 publications

Mutations in the M-Gene Segment Can Substantially Increase Replication Efficiency of NS1 Deletion Influenza A Virus in MDCK Cells

Mutations in the M-Gene Segment Can Substantially Increase Replication Efficiency of NS1 Deletion Influenza A Virus in MDCK Cells

Population balance modeling of influenza virus replication in MDCK cells during vaccine production

Induction of Apoptosis in MDCK, RK13, and Neuro-2A Cells Infected with Equine Influenza Virus

Contact Info

Product

Resources

About