Influenza A viruses alter the stability and antiviral contribution of host E3-ubiquitin ligase Mdm2 during the time-course of infection

Pizzorno, Andrés; Dubois, Julia; Machado, Daniela; Cartet, Gaëlle; Traversier, Aurélien; Julien, Thomas; Lina, Bruno; Bourdon, Jean-Christophe; Rosa‐Calatrava, Manuel; Terrier, B.

doi:10.1038/s41598-018-22139-6

Cited by 20 publications

(19 citation statements)

References 40 publications

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“…Furthermore, and similar to what some of the CoV PLpro's may do (see above in this section), Influenza NS1 was recently shown to destabilize Mdm2 E3 ligase which somehow benefits the IAV infection. According to the authors, this is because Mdm2 seems to have a p53-independent antiviral function which is then alleviated [130]. This is, however, in contrast to what was mentioned for NL63 CoV, where PLpro seems to stabilize Innate Immune Evasion by Respiratory Viruses Mdm2 to also benefit infection [124].…”

Section: Manipulation Of Ubiquitin and Isg15 Regulated Innate Immune mentioning

confidence: 91%

Innate Immune Evasion by Human Respiratory RNA Viruses

2019

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The impact of respiratory virus infections on the health of children and adults can be very significant. Yet, in contrast to most other childhood infections as well as other viral and bacterial diseases, prophylactic vaccines or effective antiviral treatments against viral respiratory infections are either still not available, or provide only limited protection. Given the widespread prevalence, a general lack of natural sterilizing immunity, and/or high morbidity and lethality rates of diseases caused by influenza, respiratory syncytial virus, coronaviruses, and rhinoviruses, this difficult situation is a genuine societal challenge. A thorough understanding of the virushost interactions during these respiratory infections will most probably be pivotal to ultimately meet these challenges. This review attempts to provide a comparative overview of the knowledge about an important part of the interaction between respiratory viruses and their host: the arms race between host innate immunity and viral innate immune eva-

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Section: Manipulation Of Ubiquitin and Isg15 Regulated Innate Immune mentioning

confidence: 91%

Innate Immune Evasion by Human Respiratory RNA Viruses

2019

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“…At the same time, there is a constant threat of newly emerging highly virulent pandemic strains. 1,2 "Vaccines have saved hundreds of millions of lives over the last century, and influenza has an important place in preventive health care programs. One estimate looking at excess deaths attributed to influenza found that, in milder influenza seasons, there were around 8 deaths per 100,000 population, while in more severe but non-pandemic years, the figure would be 44 per 100,000 3.…”

Section: Introductionmentioning

confidence: 99%

Cell culture-derived flu vaccine: Present and future

Rubio

Eiros

2018

Human Vaccines & Immunotherapeutics

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The benefit of influenza vaccines is difficult to estimate due to the complexity of accurately assessing the burden of influenza. To improve the efficacy of influenza vaccines, vaccine manufacturers have developed quadrivalent influenza vaccine (QIV) formulations for seasonal vaccination by including both influenza B lineages. Three parallel approaches for producing influenza vaccines are attracting the interest of many vaccine manufacturing companies. The first and oldest is the conventional egg-derived influenza vaccine, which is used by the current licensed influenza vaccines. The second approach is a cell culture-derived influenza vaccine, and the third and most recent is synthetic vaccines. Here, we analyze the difficulties with vaccines production in eggs and compare this to cell culture-derived influenza vaccines and discuss the future of cell culture-derived QIVs.

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“…It might be worthwhile to investigate whether the virus generates the stratagem to counteract this inhibitory effect during evolution. It has been reported that the protein level of HDM2 was not affected after infection of H3N2 in MDCK cells [31]. Interestingly, in H3N2-infected A549 cells, HDM2 expression level decreased at early stages of infection, while it is dramatically increased at 24 h post-infection [32].…”

Section: Discussionmentioning

confidence: 99%

Neddylation of M1 negatively regulates the replication of influenza A virus

Chai

Min

et al. 2020

Journal of General Virology

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Post-translational modification plays a critical role in viral replication. Previously we reported that neddylation of PB2 of influenza A virus (IAV) can inhibit viral replication. However, we found that NEDD8 overexpression can still inhibit the replication of PB2 K699R mutant viruses, implying that other viral protein(s) can be neddylated. In this study, we revealed that M1 of IAV can also be modified by NEDD8. We found that the E3 ligase HDM2 significantly promotes M1 neddylation. Furthermore, we identified M1 K187 as the major neddylation site. We generated an IAV M1 K187R mutant (WSN-M1 K187R) and compared the growth of wild-type and mutant viruses in Madin–Darby canine kidney (MDCK) cells. The data showed that the replication of WSN-M1 K187R was more efficient than that of wild-type WSN. More importantly, we observed that overexpression of NEDD8 inhibited the replication of the wild-type WSN more effectively than that of WSN-M1 K187R. In addition, we found that the neddylation-deficient M1 mutant (M1 K187R) had a longer half-life than that of wild-type M1, indicating that the neddylation of M1 reduces stability. Then we performed a viral infection assay and found that WSN-M1 K187R exhibited greater virulence in mice than wild-type WSN, suggesting that the neddylation of M1 reduced IAV replication in vivo. In conclusion, we uncovered that neddylation of M1 by HDM2 negatively regulates the stability of M1, which in turn inhibits viral replication.

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Influenza A viruses alter the stability and antiviral contribution of host E3-ubiquitin ligase Mdm2 during the time-course of infection

Cited by 20 publications

References 40 publications

Innate Immune Evasion by Human Respiratory RNA Viruses

Innate Immune Evasion by Human Respiratory RNA Viruses

Cell culture-derived flu vaccine: Present and future

Neddylation of M1 negatively regulates the replication of influenza A virus

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