Efficient influenza B virus propagation due to deficient interferon-induced antiviral activity in MDCK cells

Frensing, Timo; Seitz, C.; Heynisch, B.; Patzina, Corinna; Kochs, Georg; Reichl, Udo

doi:10.1016/j.vaccine.2011.05.069

Cited by 17 publications

(7 citation statements)

References 25 publications

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“…While previous studies have established the effects of human MxA(19) or mouse Mx1(20) proteins against human and avian IAVs, our study demonstrates an in vivo role for murine Mx1 in restricting IBV replication. This is consistent with previous reports of reduced IBV polymerase activity in the presence of Mx1 in an in vitro minireplicon system(21). Our experiments further show that Mx-mediated suppression may contribute to restriction of IBV to the URT.…”

Section: Discussionsupporting

confidence: 93%

Dissemination of influenza B virus to the lower respiratory tract of mice is restricted by the interferon response

Schwab,

Do,

Koutsakos

2023

Preprint

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The global burden of disease caused by Influenza B virus (IBV) is substantial, however IBVs remain overlooked. Understanding host-pathogen interactions as well as establishing physiologically relevant models of infection are important for the development and assessment of therapeutics and vaccines against IBV. Here, we assessed an upper respiratory tract (URT)-restricted model of mouse IBV infection, comparing it to the conventional administration of virus to the total respiratory tract (TRT). We found that URT infections with different strains of IBV resulted in limited dissemination of IBV to the lungs. Infection of the URT did not result in weight loss or systemic inflammation even at high inoculum doses and despite robust viral replication in the nose. Dissemination of IBV to the lung was enhanced in mice lacking functional type I IFN receptor (IFNAR2) but not IFNγ. Conversely, in mice expressing the IFN-inducible gene Mx1 we found reduced IBV replication in the lung and reduced dissemination of IBV from the URT to the lung. Both URT and TRT inoculation with IBV resulted in seroconversion against IBV. However, priming at the TRT conferred superior protection from a heterologous lethal IBV challenge compared to URT priming, as determined by improved survival rates and reduced viral replication throughout the respiratory tract. Overall, our study establishes a URT-restricted IBV infection model, highlights the critical role of IFNs in limiting dissemination of IBV to the lungs but also demonstrates that the lack of viral replication in the lung may impact protection from subsequent infections.ImportanceOur study investigated how IBV spreads from the nose to the lung of mice, the impact this has on disease and protection from re-infection. We found that when applied to the nose only, IBV does not spread very efficiently to the lungs in a process controlled by the interferon response. Priming immunity at the nose only was less protective from re-infection than priming immunity at both the nose and lung. These insights can guide the development of potential therapies targeting the interferon response as well as of intranasal vaccines against IBV.

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Section: Discussionsupporting

confidence: 93%

Dissemination of influenza B virus to the lower respiratory tract of mice is restricted by the interferon response

Schwab,

Do,

Koutsakos

2023

Preprint

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“…It is very important to notice that in the present case, the comparison of the MOI conditions is based only on the IVP produced. A significant number of reports describing the development of influenza cell‐based production focus rather on the total HA antigen production levels (log HA units) 49, 51–55. Therefore, direct comparison might be difficult.…”

Section: Resultsmentioning

confidence: 99%

Real‐time monitoring of influenza virus production kinetics in HEK293 cell cultures

Petiot

Kamen

2012

Biotechnology Progress

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There is an increased interest from the vaccine industry to use mammalian cell cultures for influenza vaccine manufacturing. Therefore, it became important to study the influenza infection mechanism, the viral–host interaction, and the replication kinetics from a bioprocessing stand point to maximize the influenza viral production yield in cell culture. In the present work, influenza replication kinetics was studied in HEK293 cells. Two infection conditions were evaluated, a low (0.01) and a high multiplicity of infection (1.0). Critical time points of the viral production cycle (infection, protein synthesis, viral assembly and budding, viral release, and host‐cell death) were identified in small‐scale cell cultures. Additionally, cell growth, viability, and viral titers were monitored in the viral production process. The infection state of the cultivated cell population was assessed by influenza immunolabeling throughout the culture period. Influenza virus production kinetics were also on‐line monitored by dielectric spectroscopy and successfully correlated to real‐time capacitance measures. Overall, this work provided insights into the mechanisms associated with the infection of human HEK293 cell line by the influenza virus and demonstrated, once again, the usefulness of multifrequency scanning permittivity for in‐line monitoring and supervision of cell‐based viral production processes. Published 2012 American Institute of Chemical Engineers Biotechnol. Prog., 2013

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“…A previous study also demonstrated that IFN expression suppressed the replication of different viruses, including murine NoV [ 47 ]. On the other hand, unlike immune cell and in vivo studies, MDCK cells could not demonstrate IFN-induced antiviral activity against influenza virus, which could subsequently lower antiviral defense in the cells, and promote virus replication [ 48 , 49 ]. Furthermore, ISG15 regulates the IFN -mediated antiviral immune response against different viruses, including murine NoV, influenza A, hepatitis C, and dengue viruses by covalently conjugating (ISGylation) to viral or cellular proteins to inhibit virus replication [ 50 , 51 ].…”

Section: Discussionmentioning

confidence: 99%

Human Norovirus Replication in Temperature-Optimized MDCK Cells by Forkhead Box O1 Inhibition

Jeong

Cho

Vaidya

et al. 2020

J. Microbiol. Biotechnol.

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Second, the expression levels of autophagy-, immune-, and apoptosis-related genes at 30°C and 37°C were compared to explore factors affecting HuNoV replication. HuNoV cultured at 37°C showed significantly increased autophagy-related genes ( ATG5 and ATG7 ) and immune-related genes ( IFNA , IFNB , ISG15, and NFKB ) compared to mock. However, the virus cultured at 30°C showed significantly decreased expression of autophagy-related genes ( ATG5 and ATG7 ), but not significantly different major immune-related genes ( IFNA , ISG15, and NFKB ) compared to mock. Importantly, expression of the transcription factor FOXO1 , which controls autophagy- and immune-related gene expression, was significantly lower at 30°C. Moreover, FOXO1 inhibition in temperature-optimized MDCK cells enhanced HuNoV replication, highlighting FOXO1 inhibition as an approach for successful virus replication. In the temperature-optimized cells, various HuNoV genotypes were successfully replicated, with GI.8 showing the highest replication levels followed by GII.1, GII.3, and GII.4. Furthermore, ultrastructural analysis of the infected cells revealed functional HuNoV replication at low temperature, with increased cellular apoptosis and decreased autophagic vacuoles. In conclusion, temperature-optimized MDCK cells can be used as a convenient culture model for HuNoV replication by inhibiting FOXO1 and providing adaptability to different genotypes.

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Efficient influenza B virus propagation due to deficient interferon-induced antiviral activity in MDCK cells

Cited by 17 publications

References 25 publications

Dissemination of influenza B virus to the lower respiratory tract of mice is restricted by the interferon response

Dissemination of influenza B virus to the lower respiratory tract of mice is restricted by the interferon response

Real‐time monitoring of influenza virus production kinetics in HEK293 cell cultures

Human Norovirus Replication in Temperature-Optimized MDCK Cells by Forkhead Box O1 Inhibition

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