Name: influenza a virus studies in a mouse model of infection
Uploaded: 2017-09-07T13:00:00.000+00:00
Duration: 10 min 44 s
Description: Watch this Scientific Journal Video about Influenza A Virus Studies in a Mouse Model of Infection at JoVE.com

Grip virüsü LM-S laboratuvarında araştırma kısmen New York grip Center of Excellence (NYICE), NIAID merkezleri grip araştırma ve gözetleme (CEIRS) için mükemmel bir üyesi tarafından finanse edilmektedir. Biz Wendy Bates el yazması düzeltmeler onun desteği için teşekkür ederim.

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IAV fare modeli IAV Patogenez, immünojenisite ve koruma etkinliğinin in vivo çalışmalar için yaygın olarak kullanılır. Fareler küçük boyutunu değiştirmek ve yaban gelinciği veya eskiden şiling şimdi pigs gibi hayvan diğer modeller ile karşılaştırıldığında depolamak kolaylaştırır. Ayrıca, kolaylığı açısından maliyet hayvan konut ve üreme hayvanlar çok sayıda gerekli önceden klinik aşı testlerinde kullanımlarını sağlar. Özellikle, beri fareler içinde kullanılan bird...

IAVs Orthomyxoviridae aile3' te gizli saran virüsler vardır. Onlar sekiz tek iplikçikli RNA molekülleri ile negatif polarite3içerir. Roman virüslerden insan nüfusunun4' te tanıttığında insanlarda, mevsimlik salgın hastalıklar ve ara sıra salgınları önemli sonucu IAVs neden. Ayrıca, mevsimlik IAVs yükseltilmiş bir ekonomik kayıp dünya çapında her yıl2,5üreten insanlar arasında son derece ve hızla iletilir. Öksürük, burun tıkanıklığı, ateş, kırgınlık, baş ağrısı, iştahsızlık ve miyalji IAV belirtileri içerir, ancak virüs daha ağır bir hastalık immün hastalar6' da oluşturabilir. Aslında, Dünya Sağlık Örgütü (WHO) mevsimsel grip virüsleri 300.000 500.000 ölüm dünya çapında her yıl1neden hesaplar. Şu anda gıda ve İlaç Dairesi (FDA) tarafından grip profilaksi ve insanlarda tedavisi için onaylanan ilaçların sadece iki sınıf vardır: neuraminidase (NA) inhibitörleri (örneğin, oseltamivir) ve blokerleri M2 iyon kanalının (örn., Amantadin); Ancak, ilaca dirençli virüs türevleri ortaya çıkması artan bir konusudur. Aşı, bu nedenle, insanlar IAVs enfeksiyonlarına karşı korumak için en iyi tıbbi seçenek kalır. Bugüne kadar grip üç tür insan kullanmak için FDA tarafından lisanslı aşı mevcuttur: inaktive rekombinant viral hemagglutinin (HA) protein aşılar grip aşıları (IIV) ve canlı zayıflatılmış grip aşıları (LAIV)5, 7. üç aşılar viral HA protein IAVs karşı antikor nötralize uğrak karşı adaptif immün yanıt ikna etmek için tasarlanmıştır.
IAV enfeksiyon vivo içinde çalışmaya doğrulanmış fare modeli
Hayvan modelleri, diğerleri arasında IAV Patogenez8,9,10,11, hastalık12 ve/veya viral iletim13 katkıda viral etkenler çalışma için kullanılan ,14, ve9,10,15yeni aşılar veya antiviral etkinliğini test etmek için ilaç. Fareler (Mus musculus) en yaygın kullanılan hayvan modeli IAV araştırma için birkaç nedeni vardır: 1) bağışıklık sisteminin evrimsel benzer bu mevcut insanlarda; 2) düşük maliyetli, dahil olmak üzere hayvan satın, konut ve üreme; 3) kolayca işlemek ve saklamak için küçük boyutu; 4) en az ana bilgisayar değişkenlik homojen yanıt ve sonuçları elde etmek için; 5) fareler biyoloji, genom sırası da dahil olmak üzere büyük bir bilgi; 6) birçok kullanılabilir moleküler biyoloji ve/veya İmmünoloji reaktifler; 7) viral enfeksiyon bir konağın protein katkısını çalışmaya (KO) fareler dışarı mevcut knock; ve 8) enfeksiyonları genetik temeli değerlendirmek için istismar birden çok fare suşları.
Orada birkaç fare suşları IAV vivo içindeincelemek için şu anda kullanılabilecek. Yaş, bağışıklık durumu, cinsiyet, genetik arka plan ve fare zorlanma yanı sıra yolları enfeksiyonu, doz ve viral suşları farelerde IAV enfeksiyon sonucu etkiler. Onlar iki eski suşları16,17,18yaşından, IAV hastalıklara daha duyarlı olduğundan IAV araştırmalarında kullanılan en yaygın fare suşları C57BL/6, BALB/C ve daha yakın zamanlarda, DBA.2 fareler vardır 19 , 20. önemlisi bağışıklık yanıtı da bağlı olarak fare zorlanma18,19,20farklı olabilir. Böylece, fare ve yapılacak deney için en iyi seçenek seçmek için IAV zorlanma ilişkin tüm bilgiler kurtarmak çok önemlidir.
Fare için in vivo çalışmalar IAV ile enfeksiyon iyi bir hayvan model olsa da, onlar deneysel tasarımında dikkat edilmesi gereken bazı sınırlamaları var. Örneğin, in vivo çalışmalar için fare kullanarak büyük bir sınırlama IAVs fareler arasında iletmek değil olduğunu. Böylece, aktarım için çalışmalar, daha kabul hayvan modelleri (örneğin, yaban gelinciği veya eskiden şiling şimdi pigs) kullanılan16,17,21. Buna ek olarak, farelerde IAV tezahürleri ve insanlar arasında çeşitli farklar vardır. İnsanlar farklı olarak, fare ateş IAV enfeksiyon üzerine geliştirmek mi; diğer taraftan hipotermi16,17ile mevcut. Farelerde, alt solunum yolu (akciğerler) üst solunum yolları yerine IAV çoğaltma yoğunlaşmıştır. Böylece, IAV virülans farelerde her zaman için insanlarda görülen correlated değil. Özet olarak, sınırlı dezavantajları avantajları ağır bastığı için fare grip viral Patogenez, immünojenisite ve aşı ve antiviral çalışmalarda koruyucu etkinliği değerlendirmek için kullanılan ilk hayvan modeli temsil eder. Ayrıca, bu IAV enfeksiyon bir küçük hayvan modelinde önceki kanıt olmadan büyük hayvan modeller kullanarak IAV ile çalışmalar yapmak için etik açıdan kabul edilebilir değil. Bu makale, biz fareler intranasally bulaştırmak anlatan (i.n.) IAV, önem derecesi ve viral enfeksiyon ilerlemesini izlemek nasıl ve nasıl humoral bağışıklık yanıtı ve koruma etkinliğini değerlendirmek için gerekli deneyler yürütmek için.

<table><tbody><tr><td>Madin-Darby Canine Kidney (MDCK) epithelial cells</td><td>ATCC</td><td>CCL-34</td><td></td></tr><tr><td>Six- to eight-week-old female C57BL/6 mice</td><td>National Cancer Institute (NCI)</td><td>01XBE</td><td></td></tr><tr><td>Turckey red blod cells</td><td>Biolink Inc</td><td></td><td>Store at 4 &amp;deg;C</td></tr><tr><td>Dulbecco&amp;rsquo;s modified Eagle&amp;rsquo;s medium (DMEM)</td><td>Corning Cellgro</td><td>15-013-CV</td><td>Store at 4 &amp;deg;C</td></tr><tr><td>Fetal Bovine Serum (FBS)</td><td>Seradigm</td><td>1500-050</td><td>Store at -20 &amp;deg;C</td></tr><tr><td>Penicillin/Streptomycin/L-Glutamine (PSG) 100x</td><td>Corning</td><td>30-009-CI</td><td>Store at -20 &amp;deg;C</td></tr><tr><td>Penicillin/Streptomycin (PS) 100x</td><td>Corning</td><td>30-00-CI</td><td>Store at -20 &amp;deg;C</td></tr><tr><td>Bovin Albumin solution (BA)</td><td>Sigma-Aldrich</td><td>A7409</td><td>Store at 4 &amp;deg;C</td></tr><tr><td>Bovin Serum Albumin (BSA)</td><td>Sigma-Aldrich</td><td>A9647</td><td>Store at 4 &amp;deg;C</td></tr><tr><td>Tosylsulfonyl phenylalanyl chloromethyl ketone (TPCK)-treated trypsin</td><td>Sigma-Aldrich</td><td>T8802</td><td>Store at -20 &amp;deg;C</td></tr><tr><td>Neutral Buffered Formalin 10%</td><td>EMD</td><td>65346-85</td><td>Store at RT</td></tr><tr><td>Triton X-100</td><td>J.T.Baker</td><td>X198-07</td><td>Store at RT</td></tr><tr><td>Monoclonal Antibody anti-NP Influenza A Virus HB-65</td><td>ATTC</td><td>H16-L10-4R5</td><td>Store at -20 &amp;deg;C</td></tr><tr><td>Polyclonal rabbit anti-mouse immunoglobulins/FITC</td><td>Dako</td><td>F0261</td><td>Store at 4 &amp;deg;C</td></tr><tr><td>ECL Anti-mouse IgG, Horseradish Peroxidase linked whole antibody</td><td>GE Healthcare</td><td>LNA931V/AG</td><td>Store at 4 &amp;deg;C</td></tr><tr><td>TMB substrate set</td><td>BioLegend</td><td>421101</td><td>Store at 4 &amp;deg;C</td></tr><tr><td>Vmax Kinetic plate reader</td><td>Molecular Devices</td><td></td><td></td></tr><tr><td>Dounce Tissue Grinders</td><td>Thomas Scientific</td><td>7722-7</td><td></td></tr><tr><td>Receptor destroying enzyme, RDE (II)</td><td>Denka Seiken Co.</td><td>370013</td><td>Store at -20 &amp;deg;C</td></tr><tr><td>Crystal Violet</td><td>Fisher Scienctific</td><td>C581-100</td><td>Store at RT</td></tr><tr><td>96-well Cell Culture Plate</td><td>Greiner Bio-one</td><td>655-180</td><td></td></tr><tr><td>Cell Culture dishes 100 mm</td><td>Greiner Bio-one</td><td>664-160</td><td></td></tr><tr><td>Nunc MicroWell 96-Well Microplates</td><td>Thermo Fisher Scienctific</td><td>269620</td><td></td></tr><tr><td>Nunc 96-Well Polystyrene Conical Bottom MicroWell Plates</td><td>Thermo Fisher Scienctific</td><td>249570</td><td></td></tr><tr><td>Puralub Vet Ointment</td><td>Dechra</td><td>9N-76855</td><td></td></tr><tr><td>Fluorescent microscope</td><td>Olympus</td><td>Olympus IX81</td><td></td></tr></tbody></table>

influenza a virus studies in a mouse model of infection

Grip virüsleri 500.000 ölüm dünya çapında1 neden ve 12-14 milyar USD Amerika Birleşik Devletleri tek başına doğrudan tıbbi ve hastaneye yatış masrafları ve iş devamsızlık2göz önünde bulundurarak bir yıllık ücret ile ilişkilidir. Hayvan modelleri viral Patogenez, ana bilgisayar-patojen etkileşimleri, bağışıklık yanıtı değerlendirmek için grip A virüs (IAV) çalışmalarda açısından büyük önem taşıyor ve antiviral yanı sıra geçerli ve/veya roman aşı etkinliği yaklaşıyor. Bağışıklık sistemi örümceklerle insanlarda bulunan benzer çünkü fareler bir avantajlı küçük hayvan modeli değildir, onlar are elde edilebilir--dan genetik olarak aynı konular olarak ticari satıcı, değerlendirmek için istismar birden fazla suşları vardır enfeksiyonlar, genetik temeli ve onlar are oranla ucuz ve kolay işlemek. Solunum yolları üzerinden insanlarda IAV enfeksiyon özetlemek için fareler ilk uygun Biyogüvenlik koruma altında bulaşıcı IAVs ile burunici aşılama öncesinde anestezi. Enfeksiyon sonra IAVs patogenezinde günlük (vücut kilo kaybı) morbidite ve mortalite (hayatta kalma) izleme tarafından belirlenir. Buna ek olarak, viral Patogenez Ayrıca virüs çoğaltma üst (nazal Mukoza) veya daha düşük (akciğerler) solunum yolu virüslü fareleri değerlendirmek tarafından değerlendirilebilir. Humoral yanıt üzerine IAV enfeksiyon hızla non-invaziv kanama veya değerlendirmeye ikincil antikor algılama tarafından deneyleri yönelik toplam varlığı tespit veya antikorları nötralize. Burada, fareler intranasally bulaştırmak için kullanılan ortak yöntemleri (ın) IAV ile açıklamak ve Patogenez, humoral bağışıklık yanıtı ve koruma etkinliği değerlendirin.

Fareler viral patogenezinde karakterizasyonu
IAV patogenezinde morbidite ve mortalite onun enfeksiyonu neden ilgilidir. Bu iki parametre farelerde kolayca değerlendirilebilir: IAV morbidite virüslü farelerde vücut kilo kaybı ile ilişkili ve ölüm oranı (Resim 1) hayatta kalma yüzdesini gösterir. Vücut ağırlığı ve hayatta kalma IAV enfekte farelerde genellikle her gün en az iki hafta so...

Watch this Scientific Journal Video about Influenza A Virus Studies in a Mouse Model of Infection at JoVE.com

Fare Enfeksiyon Modelinde İnfluenza A Virüsü Çalışmaları | İmmünoloji ve Enfeksiyon | Video

Influenza A Virus Studies in a Mouse Model of Infection

Grip A virüs (IAVs) önemli insan solunum patojenler vardır. İnsan fizyolojisi taklit hayvan modelleri IAVs patojenitesi anlamak ve preklinik roman aşı yaklaşımlar sınamasını gerçekleştirmek için gereklidir. Burada, biz IAV Patogenez, humoral yanıt ve enfeksiyon bir fare modeli kullanarak aşı etkinliğini değerlendirmek için teknikler açıklanmaktadır.

Grip A virüs enfeksiyonu bir fare modeli çalışmalarda

Influenza viruses cause over 500,000 deaths worldwide1 and are associated with an annual cost of 12 - 14 billion USD in the United States alone ...

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28.2K Görüntüleme.  University of Rochester School of Medicine and Dentistry. Grip A virüs (IAVs) önemli insan solunum patojenler vardır. İnsan fizyolojisi taklit hayvan modelleri IAVs patojenitesi anlamak ve preklinik roman aşı yaklaşımlar sınamasını gerçekleştirmek için gereklidir. Burada, biz IAV Patogenez, humoral yanıt ve enfeksiyon bir fare modeli kullanarak aşı etkinliğini değerlendirmek için teknikler açıklanmaktadır.

Video: Influenza A Virus Studies in a Mouse Model of Infection

Using Bioluminescent Imaging to Investigate Synergism Between Streptococcus pneumoniae and Influenza A Virus in Infant Mice

During the 1918 influenza virus pandemic, which killed approximately 50 million people worldwide, the majority of fatalities were not the result of infection with influenza virus alone. Instead, most individuals are thought to have succumbed to a secondary bacterial infection, predominately caused by the bacterium Streptococcus pneumoniae (the pneumococcus). The synergistic relationship between infections caused by influenza virus and the pneumococcus has subsequently been observed during the 1957 Asian influenza virus pandemic, as well as during seasonal outbreaks of the virus (reviewed in 1, 2). Here, we describe a protocol used to investigate the mechanism(s) that may be involved in increased morbidity as a result of concurrent influenza A virus and S. pneumoniae infection. We have developed an infant murine model to reliably and reproducibly demonstrate the effects of influenza virus infection of mice colonised with S. pneumoniae. Using this protocol, we have provided the first insight into the kinetics of pneumococcal transmission between co-housed, neonatal mice using in vivo imaging 3.

Using Bioluminescent Imaging to Investigate Synergism Between Streptococcus pneumoniae and Influenza A Virus in Infant Mice

A concurrent infection with influenza A virus is one of the factors implicated in the induction of invasive pneumococcal disease during asymptomatic Streptococcus pneumoniae carriage. Here we describe a mixed infection method using infant mice to investigate the synergism between these two respiratory pathogens.

Yılları arasında sinerjistik Araştırma Bioluminescent Görüntüleme kullanma Streptococcus pneumoniae Bebek Fare ve İnfluenza A Virüsü

During the 1918 influenza virus pandemic, which killed approximately 50 million people worldwide, the majority of fatalities were not the result of ...

İmmünoloji ve Enfeksiyon

High-throughput Detection Method for Influenza Virus

Influenza virus is a respiratory pathogen that causes a high degree of morbidity and mortality every year in multiple parts of the world. Therefore, precise diagnosis of the infecting strain and rapid high-throughput screening of vast numbers of clinical samples is paramount to control the spread of pandemic infections. Current clinical diagnoses of influenza infections are based on serologic testing, polymerase chain reaction, direct specimen immunofluorescence and cell culture 1,2.
Here, we report the development of a novel diagnostic technique used to detect live influenza viruses. We used the mouse-adapted human A/PR/8/34 (PR8, H1N1) virus 3 to test the efficacy of this technique using MDCK cells 4. MDCK cells (104 or 5 x 103 per well) were cultured in 96- or 384-well plates, infected with PR8 and viral proteins were detected using anti-M2 followed by an IR dye-conjugated secondary antibody. M2 5 and hemagglutinin 1 are two major marker proteins used in many different diagnostic assays. Employing IR-dye-conjugated secondary antibodies minimized the autofluorescence associated with other fluorescent dyes. The use of anti-M2 antibody allowed us to use the antigen-specific fluorescence intensity as a direct metric of viral quantity. To enumerate the fluorescence intensity, we used the LI-COR Odyssey-based IR scanner. This system uses two channel laser-based IR detections to identify fluorophores and differentiate them from background noise. The first channel excites at 680 nm and emits at 700 nm to help quantify the background. The second channel detects fluorophores that excite at 780 nm and emit at 800 nm. Scanning of PR8-infected MDCK cells in the IR scanner indicated a viral titer-dependent bright fluorescence. A positive correlation of fluorescence intensity to virus titer starting from 102-105 PFU could be consistently observed. Minimal but detectable positivity consistently seen with 102-103 PFU PR8 viral titers demonstrated the high sensitivity of the near-IR dyes. The signal-to-noise ratio was determined by comparing the mock-infected or isotype antibody-treated MDCK cells.
Using the fluorescence intensities from 96- or 384-well plate formats, we constructed standard titration curves. In these calculations, the first variable is the viral titer while the second variable is the fluorescence intensity. Therefore, we used the exponential distribution to generate a curve-fit to determine the polynomial relationship between the viral titers and fluorescence intensities. Collectively, we conclude that IR dye-based protein detection system can help diagnose infecting viral strains and precisely enumerate the titer of the infecting pathogens.

This method describes the use of Infrared dye based imaging system for detection of H1N1 in bronchioalveolar lavage (BAL) fluid of infected mice at a high sensitivity. This methodology can be performed in a 96- or 384-well plate, requires &lt;10 &mu;l volume of test material and has the potential for concurrent screening of multiple pathogens.

Gribi için yüksek verimlilik Tespit Yöntemi

Influenza virus is a respiratory pathogen that causes a high degree of morbidity and mortality every year in multiple parts of the world. Therefore, ...

Intranasal Administration of Recombinant Influenza Vaccines in Chimeric Mouse Models to Study Mucosal Immunity

Vaccines are one of the greatest achievements of mankind, and have saved millions of lives over the last century. Paradoxically, little is known about the physiological mechanisms that mediate immune responses to vaccines perhaps due to the overall success of vaccination, which has reduced interest into the molecular and physiological mechanisms of vaccine immunity. However, several important human pathogens including influenza virus still pose a challenge for vaccination, and may benefit from immune-based strategies. 
Although influenza reverse genetics has been successfully applied to the generation of live-attenuated influenza vaccines (LAIVs), the addition of molecular tools in vaccine preparations such as tracer components to follow up the kinetics of vaccination in vivo, has not been addressed. In addition, the recent generation of mouse models that allow specific depletion of leukocytes during kinetic studies has opened a window of opportunity to understand the basic immune mechanisms underlying vaccine-elicited protection. Here, we describe how the combination of reverse genetics and chimeric mouse models may help to provide new insights into how vaccines work at physiological and molecular levels, using as example a recombinant, cold-adapted, live-attenuated influenza vaccine (LAIV). We utilized laboratory-generated LAIVs harboring cell tracers as well as competitive bone marrow chimeras (BMCs) to determine the early kinetics of vaccine immunity and the main physiological mechanisms responsible for the initiation of vaccine-specific adaptive immunity. In addition, we show how this technique may facilitate gene function studies in single animals during immune responses to vaccines. We propose that this technique can be applied to improve current prophylactic strategies against pathogens for which urgent medical countermeasures are needed, for example influenza, HIV, Plasmodium, and hemorrhagic fever viruses such as Ebola virus.

There is an overall lack of knowledge about how vaccines work. Here we propose the combined use of reverse genetics and bone marrow chimeric mice to gain insight into the early host immune responses to vaccines with a special focus on dendritic cells and T cell immunity.

Kimerik fare modellerinde Rekombinant Grip aşıların burun içinde yoluyla mukozal bağışıklık Okumak

Vaccines are one of the greatest achievements of mankind, and have saved millions of lives over the last century. Paradoxically, little is known about the ...

Co-immunoprecipitation of the Mouse Mx1 Protein with the Influenza A Virus Nucleoprotein

Studying the interaction between proteins is key in understanding their function(s). A very powerful method that is frequently used to study interactions of proteins with other macromolecules in a complex sample is called co-immunoprecipitation. The described co-immunoprecipitation protocol allows to demonstrate and further investigate the interaction between the antiviral myxovirus resistance protein 1 (Mx1) and one of its viral targets, the influenza A virus nucleoprotein (NP). The protocol starts with transfected mammalian cells, but it is also possible to use influenza A virus infected cells as starting material. After cell lysis, the viral NP protein is pulled-down with a specific antibody and the resulting immune-complexes are precipitated with protein G beads. The successful pull-down of NP and the co-immunoprecipitation of the antiviral Mx1 protein are subsequently revealed by western blotting. A prerequisite for successful co-immunoprecipitation of Mx1 with NP is the presence of N-ethylmaleimide (NEM) in the cell lysis buffer. NEM alkylates free thiol groups. Presumably this reaction stabilizes the weak and/or transient NP&#8211;Mx1 interaction by preserving a specific conformation of Mx1, its viral target or an unknown third component. An important limitation of co-immunoprecipitation experiments is the inadvertent pull-down of contaminating proteins, caused by nonspecific binding of proteins to the protein G beads or antibodies. Therefore, it is very important to include control settings to exclude false positive results. The described co-immunoprecipitation protocol can be used to study the interaction of Mx proteins from different vertebrate species with viral proteins, any pair of proteins, or of a protein with other macromolecules. The beneficial role of NEM to stabilize weak and/or transient interactions needs to be tested for each interaction pair individually.

This co-immunoprecipitation protocol allows to study the interaction between the influenza A virus nucleoprotein and the antiviral Mx1 protein in human cells. The protocol emphasizes the importance of N-ethylmaleimide for successful co-immunoprecipitation of Mx1 and influenza A virus nucleoprotein.

İnfluenza A virüsü nükleoproteini Fare MX1 Protein Co-immunopresipitasyonu

Studying the interaction between proteins is key in understanding their function(s). A very powerful method that is frequently used to study interactions ...

Using Zebrafish Models of Human Influenza A Virus Infections to Screen Antiviral Drugs and Characterize Host Immune Cell Responses

Each year, seasonal influenza outbreaks profoundly affect societies worldwide. In spite of global efforts, influenza remains an intractable healthcare burden. The principle strategy to curtail infections is yearly vaccination. In individuals who have contracted influenza, antiviral drugs can mitigate symptoms. There is a clear and unmet need to develop alternative strategies to combat influenza. Several animal models have been created to model host-influenza interactions. Here, protocols for generating zebrafish models for systemic and localized human influenza A virus (IAV) infection are described. Using a systemic IAV infection model, small molecules with potential antiviral activity can be screened. As a proof-of-principle, a protocol that demonstrates the efficacy of the antiviral drug Zanamivir in IAV-infected zebrafish is described. It shows how disease phenotypes can be quantified to score the relative efficacy of potential antivirals in IAV-infected zebrafish. In recent years, there has been increased appreciation for the critical role neutrophils play in the human host response to influenza infection. The zebrafish has proven to be an indispensable model for the study of neutrophil biology, with direct impacts on human medicine. A protocol to generate a localized IAV infection in the Tg(mpx:mCherry) zebrafish line to study neutrophil biology in the context of a localized viral infection is described. Neutrophil recruitment to localized infection sites provides an additional quantifiable phenotype for assessing experimental manipulations that may have therapeutic applications. Both zebrafish protocols described faithfully recapitulate aspects of human IAV infection. The zebrafish model possesses numerous inherent advantages, including high fecundity, optical clarity, amenability to drug screening, and availability of transgenic lines, including those in which immune cells such as neutrophils are labeled with fluorescent proteins. The protocols detailed here exploit these advantages and have the potential to reveal critical insights into host-IAV interactions that may ultimately translate into the clinic.

Systemic and localized zebrafish infection models for human influenza A virus are demonstrated. Using a systemic infection model, zebrafish can be used to screen antiviral drugs. Using a localized infection model, zebrafish can be used to characterize host immune cell responses.

İnsan İnfluenza A Virüs Enfeksiyonları Zebra balığı Modeller Kullanılarak Antiviral İlaçlar Ekran ve Host Bağışıklık Hücre Yanıtları karakterize etmek

Each year, seasonal influenza outbreaks profoundly affect societies worldwide. In spite of global efforts, influenza remains an intractable healthcare ...

Imaging Cell Interaction in Tracheal Mucosa During Influenza Virus Infection Using Two-photon Intravital Microscopy

The analysis of cell-cell or cell-pathogen interaction in vivo is an important tool to understand the dynamics of the immune response to infection. Two-photon intravital microscopy (2P-IVM) allows the observation of cell interactions in deep tissue in living animals, while minimizing the photobleaching generated during image acquisition. To date, different models for 2P-IVM of lymphoid and non-lymphoid organs have been described. However, imaging of respiratory organs remains a challenge due to the movement associated with the breathing cycle of the animal.
Here, we describe a protocol to visualize in vivo immune cell interactions in the trachea of mice infected with influenza virus using 2P-IVM. To this purpose, we developed a custom imaging platform, which included the surgical exposure and intubation of the trachea, followed by the acquisition of dynamic images of neutrophils and dendritic cells (DC) in the mucosal epithelium. Additionally, we detailed the steps needed to perform influenza intranasal infection and flow cytometric analysis of immune cells in the trachea. Finally, we analyzed neutrophil and DC motility as well as their interactions during the course of a movie. This protocol allows for the generation of stable and bright 4D images necessary for the assessment of cell-cell interactions in the trachea.

In this study, we present a protocol to perform two-photon intravital imaging and cell interaction analysis in the murine tracheal mucosa after infection with influenza virus. This protocol will be relevant for researchers studying immune cell dynamics during respiratory infections.

İki fotonlu Intravital mikroskobu kullanılarak grip virüsü enfeksiyonu sırasında trakeal mukozasında görüntüleme hücre etkileşimi

The analysis of cell-cell or cell-pathogen interaction in vivo is an important tool to understand the dynamics of the immune response to infection. ...

A Murine Model of Dengue Virus-induced Acute Viral Encephalitis-like Disease

Dengue virus (DENV), an arthropod-borne virus transmitted by mosquitoes, may cause the severe disease known as dengue hemorrhagic fever, which is characterized by lethal complications due to plasma leakage, ascites, pleural effusion, respiratory distress, severe bleeding, and organ impairment. A few cases of DENV infection present neurological manifestations; however, studies have not explored DENV-induced neuropathogenesis further. In this study, we present a protocol to use an immunocompetent outbred ICR (Institute of Cancer Research) mouse for investigating the induction of central nervous system (CNS) infection with DENV, followed by the progression of acute viral encephalitis-like disease.

Here, we present a protocol for creating an immunocompetent ICR (Institute of Cancer Research) murine model of central nervous system infection to display the development of neuropathy. Monitoring acute viral encephalitic disorders by identical disease scores could be performed for showing dengue virus-induced neuropathy in vivo.

Dang humması virüs kaynaklı akut viral Ensefalitis-benzeri hastalık bir Murine modeli

Dengue virus (DENV), an arthropod-borne virus transmitted by mosquitoes, may cause the severe disease known as dengue hemorrhagic fever, which is ...

A Luciferase-fluorescent Reporter Influenza Virus for Live Imaging and Quantification of Viral Infection

Influenza A viruses (IAVs) cause human respiratory disease that is associated with significant health and economic consequences. As with other viruses, studying IAV requires the use of laborious secondary approaches to detect the presence of the virus in infected cells and/or in animal models of infection. This limitation has been recently circumvented with the generation of recombinant IAVs expressing easily traceable fluorescent or bioluminescent (luciferase) reporter proteins. However, researchers have been forced to select fluorescent or luciferase reporter genes due to the restricted capacity of the IAV genome for including foreign sequences. To overcome this limitation, we have generated a recombinant replication-competent bi-reporter IAV (BIRFLU) stably expressing both a fluorescent and a luciferase reporter gene to easily track IAV infections in vitro and in vivo. To this end, the viral non-structural (NS) and hemagglutinin (HA) viral segments of influenza A/Puerto Rico/8/34 H1N1 (PR8) were modified to encode the fluorescent Venus and the bioluminescent Nanoluc luciferase proteins, respectively. Here, we describe the use of BIRFLU in a mouse model of IAV infection and the detection of both reporter genes using an in vivo imaging system. Notably, we have observed a good correlation between the expressions of both reporters and viral replication. The combination of cutting-edge techniques in molecular biology, animal research and imaging technologies, provides researchers the unique opportunity to use this tool for influenza research, including the study of virus-host interactions and dynamics of viral infections. Importantly, the feasibility to genetically alter the viral genome to express two foreign genes from different viral segments opens up opportunities to use this approach for: (i) the development of novel IAV vaccines, (ii) the generation of recombinant IAVs that can be used as vaccine vectors for the treatment of other human pathogen infections.

Influenza A viruses (IAVs) are contagious respiratory pathogens that cause annual epidemics and occasional pandemics. Here, we describe a protocol to track viral infections in vivo using a novel recombinant luciferase and fluorescence-expressing bi-reporter IAV (BIRFLU). This approach provides researchers with an excellent tool to study IAV in vivo.

Canlı Görüntüleme ve Viral Enfeksiyon Quantification için Bir Luciferase-floresan Reporter Grip Virüsü

Influenza A viruses (IAVs) cause human respiratory disease that is associated with significant health and economic consequences. As with other viruses, ...

Evaluation of T Follicular Helper Cells and Germinal Center Response During Influenza A Virus Infection in Mice

T Follicular Helper (Tfh) cells are an independent CD4+&#160;T cell subset specialized in providing help for germinal center (GC) development and generation of high-affinity antibodies. In influenza virus infection, robust Tfh and GC B cell responses are induced to facilitate effective virus eradication, which confers a qualified mouse model for Tfh-associated study. In this paper, we described protocols in detection of basic Tfh-associated immune response during influenza virus infection in mice. These protocols include: intranasal inoculation of influenza virus; flow cytometry staining and analysis of polyclonal and antigen-specific Tfh cells, GC B cells and plasma cells; immunofluorescence detection of GCs; enzyme-linked immunosorbent assay (ELISA) of influenza virus-specific antibody in serum. These assays basically quantify the differentiation and function of Tfh cells in influenza virus infection, thus providing help for studies in elucidating differentiation mechanism and manipulation strategy.

This paper describes protocols of evaluating Tfh and GC B response in mouse model of influenza virus infection.

Farelerde grip A Virüs Enfeksiyonu Sırasında T Foliküler Yardımcı Hücrelerin ve Germinal Merkez Yanıtının Değerlendirilmesi

T Follicular Helper (Tfh) cells are an independent CD4+&#160;T cell subset specialized in providing help for germinal center (GC) development and ...

A Mouse Model for the Transition of Streptococcus pneumoniae from Colonizer to Pathogen upon Viral Co-Infection Recapitulates Age-Exacerbated Illness

Streptococcus pneumoniae (pneumococcus) is an asymptomatic colonizer of the nasopharynx in most individuals but can progress to a pulmonary and systemic pathogen upon influenza A virus (IAV) infection. Advanced age enhances host susceptibility to secondary pneumococcal pneumonia and is associated with worsened disease outcomes. The host factors driving those processes are not well defined, in part due to a lack of animal models that reproduce the transition from asymptomatic colonization to severe clinical disease. 
This paper describes a novel mouse model that recreates the transition of pneumococci from asymptomatic carriage to disease upon viral infection. In this model, mice are first intranasally inoculated with biofilm-grown pneumococci to establish asymptomatic carriage, followed by IAV infection of both the nasopharynx and lungs. This results in bacterial dissemination to the lungs, pulmonary inflammation, and obvious signs of illness that can progress to lethality. The degree of disease is dependent on the bacterial strain and host factors. 
Importantly, this model reproduces the susceptibility of aging, because compared to young mice, old mice display more severe clinical illness and succumb to disease more frequently. By separating carriage and disease into distinct steps and providing the opportunity to analyze the genetic variants of both the pathogen and the host, this S. pneumoniae/IAV co-infection model permits the detailed examination of the interactions of an important pathobiont with the host at different phases of disease progression. This model can also serve as an important tool for identifying potential therapeutic targets against secondary pneumococcal pneumonia in susceptible hosts.

A Mouse Model for the Transition of Streptococcus pneumoniae from Colonizer to Pathogen upon Viral Co-Infection Recapitulates Age-Exacerbated Illness

This paper describes a novel mouse model for the transition of pneumococcus from an asymptomatic colonizer to a disease-causing pathogen during viral infection. This model can be readily adapted to study polymicrobial and host-pathogen interactions during the different phases of disease progression and across various hosts.

Streptococcus pneumoniae'nin Viral Ko-Enfeksiyon Üzerine Kolonizatörden Patojene Geçişi İçin Bir Fare Modeli, Yaşın Şiddetlendirdiği Hastalıkları Özetler

Streptococcus pneumoniae (pneumococcus) is an asymptomatic colonizer of the nasopharynx in most individuals but can progress to a pulmonary and systemic ...

Grip A virüs enfeksiyonu bir fare modeli çalışmalarda

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