Ion-Current-Based Temporal Proteomic Profiling of Influenza-A-Virus-Infected Mouse Lungs Revealed Underlying Mechanisms of Altered Integrity of the Lung Microvascular Barrier

2016 ◽  
Vol 15 (2) ◽  
pp. 540-553 ◽  
Author(s):  
Shichen Shen ◽  
Jun Li ◽  
Shannon Hilchey ◽  
Xiaomeng Shen ◽  
Chengjian Tu ◽  
...  
Keyword(s):  
Infected Mouse ◽  
Influenza A Virus ◽  
Influenza A ◽  
Ion Current ◽  
Proteomic Profiling ◽  
Underlying Mechanisms ◽  
Mouse Lungs

scholarly journals STUDIES ON INFLUENZA VIRUS

1941 ◽  
Vol 73 (5) ◽  
pp. 581-599 ◽  
Author(s):  
Edwin H. Lennette ◽  
Frank L. Horsfall
Keyword(s):  
Influenza Virus ◽  
Chick Embryo ◽  
Influenza A Virus ◽  
Influenza A ◽  
Complement Fixation ◽  
Soluble Antigen ◽  
Swine Virus ◽  
Specific Fixation ◽  
Mouse Lungs

Influenza complement fixation tests designed for use with ferret serum are described. Complement-fixing antigens derived from influenza ferret lungs were unsatisfactory due to their low content of soluble antigen; those prepared from mouse lungs or developing chick embryo membranes proved to be better antigenically and were reliable when the various reagents in the test were properly adjusted to eliminate non-specific fixation of complement. The results of cross complement fixation tests indicated that the soluble antigens of the PR8 and W.S. strains of influenza A virus were closely similar, if not identical. They indicated also that the soluble antigen of swine virus possessed components present in the antigens of the human strains of virus.

scholarly journals Influenza A Virus Inhibits RSV Infection via a Two-Wave Expression of IFIT Proteins

Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1171
Author(s):  
Yaron Drori ◽  
Jasmine Jacob-Hirsch ◽  
Rakefet Pando ◽  
Aharona Glatman-Freedman ◽  
Nehemya Friedman ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Influenza Viruses ◽  
Mass Spectrometry Analysis ◽  
Influenza A Viruses ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Mouse Lungs

Influenza viruses and respiratory syncytial virus (RSV) are respiratory viruses that primarily circulate worldwide during the autumn and winter seasons. Seasonal surveillance has shown that RSV infection generally precedes influenza. However, in the last four winter seasons (2016–2020) an overlap of the morbidity peaks of both viruses was observed in Israel, and was paralleled by significantly lower RSV infection rates. To investigate whether the influenza A virus inhibits RSV, human cervical carcinoma (HEp2) cells or mice were co-infected with influenza A and RSV. Influenza A inhibited RSV growth, both in vitro and in vivo. Mass spectrometry analysis of mouse lungs infected with influenza A identified a two-wave pattern of protein expression upregulation, which included members of the interferon-induced protein with the tetratricopeptide (IFITs) family. Interestingly, in the second wave, influenza A viruses were no longer detectable in mouse lungs. In addition, knockdown and overexpression of IFITs in HEp2 cells affected RSV multiplicity. In conclusion, influenza A infection inhibits RSV infectivity via upregulation of IFIT proteins in a two-wave modality. Understanding the immune system involvement in the interaction between influenza A and RSV viruses will contribute to the development of future treatment strategies against these viruses.

scholarly journals RNA-Sequencing-Based Transcriptomic Analysis Reveals a Role for Annexin-A1 in Classical and Influenza A Virus-Induced Autophagy

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1399 ◽  
Author(s):  
Jianzhou Cui ◽  
Dhakshayini Morgan ◽  
Dao Han Cheng ◽  
Sok Lin Foo ◽  
Gracemary L. R. Yap ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A Virus ◽  
Influenza A ◽  
Influenza Infection ◽  
Critical Role ◽  
Mtor Inhibitors ◽  
Influenza Viruses ◽  
Annexin A1 ◽  
Underlying Mechanisms

Influenza viruses have been shown to use autophagy for their survival. However, the proteins and mechanisms involved in the autophagic process triggered by the influenza virus are unclear. Annexin-A1 (ANXA1) is an immunomodulatory protein involved in the regulation of the immune response and Influenza A virus (IAV) replication. In this study, using clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 (CRISPR associated protein 9) deletion of ANXA1, combined with the next-generation sequencing, we systematically analyzed the critical role of ANXA1 in IAV infection as well as the detailed processes governing IAV infection, such as macroautophagy. A number of differentially expressed genes were uniquely expressed in influenza A virus-infected A549 parental cells and A549 ∆ANXA1 cells, which were enriched in the immune system and infection-related pathways. Gene ontology and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway revealed the role of ANXA1 in autophagy. To validate this, the effect of mechanistic target of rapamycin (mTOR) inhibitors, starvation and influenza infection on autophagy was determined, and our results demonstrate that ANXA1 enhances autophagy induced by conventional autophagy inducers and influenza virus. These results will help us to understand the underlying mechanisms of IAV infection and provide a potential therapeutic target for restricting influenza viral replication and infection.

scholarly journals QUANTITATIVE ASPECTS OF THE MULTIPLICATION OF INFLUENZA A VIRUS IN THE MOUSE LUNG

1952 ◽  
Vol 95 (2) ◽  
pp. 135-145 ◽  
Author(s):  
Harold S. Ginsberg ◽  
Frank L. Horsfall
Keyword(s):  
Infected Mouse ◽  
Influenza A Virus ◽  
Influenza A ◽  
Fold Increase ◽  
Mouse Lung ◽  
Quantitative Investigation ◽  
Pulmonary Lesions ◽  
A Value ◽  
Rate Of Increase ◽  
Constant Rate

Influenza A virus, PR8 strain, increases in amount in the infected mouse lung at a relatively constant rate. When more than 25 M.S.50 doses of virus is inoculated, the rate of multiplication appears to be independent of the amount of virus introduced; has a value of 1,100-fold increase per day. The rate of increase in the pulmonary lesions induced by infection of the mouse lung with PR8 also appears to be relatively constant and independent of the amount of virus inoculated; has a value of 8.5-fold increase per day. The essential variables in the PR8-mouse lung system appear to be equated satisfactorily by functions which were derived previously (4) during a similar quantitative investigation on pneumonia virus of mice (PVM). Evidence in support of the hypothesis that the processes of multiplication of PR8 and PVM are different in the mouse lung is presented.

scholarly journals Strong interferon-inducing capacity of a highly virulent variant of influenza A virus strain PR8 with deletions in the NS1 gene

2009 ◽  
Vol 90 (12) ◽  
pp. 2990-2994 ◽  
Author(s):  
Georg Kochs ◽  
Luis Martínez-Sobrido ◽  
Stefan Lienenklaus ◽  
Siegfried Weiss ◽  
Adolfo García-Sastre ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Influenza Viruses ◽  
Ns1 Protein ◽  
Efficient Induction ◽  
Ns1 Gene ◽  
Mouse Lungs ◽  
Highly Virulent ◽  
Complete Deletion

Influenza viruses lacking the interferon (IFN)-antagonistic non-structural NS1 protein are strongly attenuated. Here, we show that mutants of a highly virulent variant of A/PR/8/34 (H1N1) carrying either a complete deletion or C-terminal truncations of NS1 were far more potent inducers of IFN in infected mice than NS1 mutants derived from standard A/PR/8/34. Efficient induction of IFN correlated with successful initial virus replication in mouse lungs, indicating that the IFN response is boosted by enhanced viral activity. As the new NS1 mutants can be handled in standard biosafety laboratories, they represent convenient novel tools for studying virus-induced IFN expression in vivo.

Inhibitory Effects of an Antisense Oligonucleotide in an Experimentally Infected Mouse Model of Influenza A Virus

2000 ◽  
Vol 279 (1) ◽  
pp. 158-161 ◽  
Author(s):  
Tadashi Mizuta ◽  
Masatoshi Fujiwara ◽  
Takayuki Abe ◽  
Naoko Miyano-Kurosaki ◽  
Tomoyuki Yokota ◽  
...  
Keyword(s):  
Mouse Model ◽  
Infected Mouse ◽  
Influenza A Virus ◽  
Antisense Oligonucleotide ◽  
Influenza A ◽  
Inhibitory Effects

scholarly journals Histone Deacetylase 6 Knockout Mice Exhibit Higher Susceptibility to Influenza A Virus Infection

Viruses ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 728 ◽  
Author(s):  
Mark Zanin ◽  
Jennifer DeBeauchamp ◽  
Gowthami Vangala ◽  
Richard J. Webby ◽  
Matloob Husain
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Histone Deacetylase ◽  
Influenza A Virus ◽  
Influenza A ◽  
Antiviral Response ◽  
Histone Deacetylase 6 ◽  
Influenza A Virus Infection ◽  
Innate Antiviral Response ◽  
Mouse Lungs

The host innate defence against influenza virus infection is an intricate system with a plethora of antiviral factors involved. We have identified host histone deacetylase 6 (HDAC6) as an anti-influenza virus factor in cultured cells. Consistent with this, we report herein that HDAC6 knockout (KO) mice are more susceptible to influenza virus A/PR/8/1934 (H1N1) infection than their wild type (WT) counterparts. The KO mice lost weight faster than the WT mice and, unlike WT mice, could not recover their original body weight. Consequently, more KO mice succumbed to infection, which corresponded with higher lung viral loads. Conversely, the expression of the critical innate antiviral response genes interferon alpha/beta, CD80, CXCL10 and IL15 was significantly downregulated in KO mouse lungs compared to WT mouse lungs. These data are consistent with the known function of HDAC6 of de-acetylating the retinoic acid inducible gene-I (RIG-I) and activating the host innate antiviral response cascade. Loss of HDAC6 thus leads to a blunted innate response and increased susceptibility of mice to influenza A virus infection.

scholarly journals Generation of an Influenza A Virus Vector Expressing Biologically Active Human Interleukin-2 from the NS Gene Segment

2005 ◽  
Vol 79 (16) ◽  
pp. 10672-10677 ◽  
Author(s):  
Christian Kittel ◽  
Boris Ferko ◽  
Martina Kurz ◽  
Regina Voglauer ◽  
Sabine Sereinig ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A Virus ◽  
Influenza A ◽  
Interleukin 2 ◽  
Virus Vector ◽  
Biologically Active ◽  
Ns1 Protein ◽  
Reading Frame ◽  
Ns Gene ◽  
Mouse Lungs

ABSTRACT Engineering of the influenza A virus NS1 protein became an attractive approach to the development of influenza vaccine vectors since it can tolerate large inserts of foreign proteins. However, influenza virus vectors expressing long foreign sequences from the NS1 open reading frame (ORF) are usually replication deficient in animals due to the abrogation of their NS1 protein function. In this study, we describe a bicistronic expression strategy based on the insertion of an overlapping UAAUG stop-start codon cassette into the NS gene, allowing the reinitiation of translation of a foreign sequence. Although the expression level of green fluorescent protein (GFP) from the newly created reading frame was significantly lower than that obtained previously from an influenza virus vector expressing GFP from the NS1 ORF, the bicistronic vector appeared to be replication competent in mice and showed outstanding genetic stability. All viral isolates derived from mouse lungs at 10 days postinfection were still capable of expressing GFP in infected cells. Utilizing this bicistronic approach, we constructed another recombinant influenza virus, allowing the secretion of biologically active human interleukin-2 (IL-2). Although this virus also replicated to high titers in mouse lungs, it did not display any mortality rate in infected animals, in contrast to control viruses. Moreover, the IL-2-expressing virus showed an enhanced CD8+ response to viral antigens in mice after a single intranasal immunization. These results indicate that influenza viruses could be engineered for the expression of biologically active molecules such as cytokines for immune modulation purposes.

scholarly journals ResolvinD1 Protects the Airway Barrier Against Injury Induced by Influenza A Virus Through the Nrf2 Pathway

2021 ◽  
Vol 10 ◽  
Author(s):  
Yan Guo ◽  
You-Hui Tu ◽  
Xu Wu ◽  
Shuang Ji ◽  
Ji-Long Shen ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
In Vivo Studies ◽  
Lipid Mediator ◽  
Protective Effects ◽  
Inflammatory Reactions ◽  
Nrf2 Pathway ◽  
Underlying Mechanisms ◽  
E Cadherin

Airway barrier damage and excessive inflammation induced by influenza A virus (IAV) are associated with disease progression and prognosis. ResolvinD1 (RvD1) is a promising lipid mediator with critical protection against infection in the lung. However, whether RvD1 protects against IAV-induced injury and the underlying mechanisms remain elusive. In this study, primary normal human bronchial epithelial (pNHBE) cells were isolated and co-cultured with IAV and/or RvD1. Then, the expressions of E-cadherin, Zonula occludins-1, inflammatory mediators and proteins in Nrf2-dependent pathway were detected. To further explore the mechanisms, Nrf2 short hairpin RNA (Nrf2 shRNA) was applied in pNHBE cells. Furthermore, mice were infected with IAV, and were subsequently treated with RvD1. We found that IAV downregulated expressions of E-cadherin, Zonula occludins-1, Nrf2 and HO-1, upregulated the phosphorylation of NF κ B p65 and IKBα, levels of IL-8 and TNF-α, as well as ROS production. RvD1 reversed these damaging effects induced by IAV. However, when Nrf2 expression was suppressed with shRNA in pNHBE cells, the protective effects of RvD1 on IAV-induced injury were inhibited. In vivo studies further demonstrated that RvD1 could alleviate barrier protein breakdown and reduce airway inflammatory reactions. Collectively, the study demonstrated that RvD1 could play dual beneficial roles in protecting airway epithelium barrier function and reducing inflammation via the Nrf2 pathway, which may provide a better treatment option for influenza A virus infection.

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