LM-S 실험실에서 인플루엔자 바이러스에 대 한 연구는 부분적으로 뉴욕 인플루엔자의 우수 센터 (NYICE), 인플루엔자 연구 및 감시 (CEIRS)의 NIAID 센터의 회원에 의해 자금. 원고 수정에 그녀의 지원에 감사 웬디 베이츠 하 고.

<ol>
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저자는 공개 없다.

IAV의 마우스 모델 IAV pathogenesis, immunogenicity 및 보호 효능의 학문 vivo에서 널리 사용 됩니다. 쥐의 작은 크기 쉽게 그들을 조작 하 고 흰 족제비 또는 기니 돼지 등 다른 동물 모델에 비해 저장. 또한, 동물 비용 측면에서 용이성, 주택 및 재생 그들의 사용에에서 허용 전 임상 예방 접종 시험 동물의 다 수 필요 하다. 특히, 마우스에서 사용 된 이후 여러 연구 분야, 몇몇 분자 되며 면역학 murine ?...

IAVs 엔벌로프된 바이러스 Orthomyxoviridae 가족3으로 분류 되는. 그들은 부정적인 극성3와 8 개의 단일 가닥 RNA 분자를 포함. 인간에서는, IAVs 소설은 바이러스가 인간의 인구4에 소개 될 때 계절 전염병과 중요 한 결과의 가끔 전염병 발생할. 또한, 계절 IAVs 매우 고 빠르게 전송 됩니다 모든 년2,5는 높은 경제 손실 전세계 생산 인간 사이. IAV 증상은 기침, 코 막힘, 발열, 불쾌, 두통, 거식 증과 근육 통, 하지만 바이러스 또한 immunocompromised 환자6에서 더 심각한 질병을 일으킬 수 있다. 사실, 세계 보건 기구 (WHO)는 계절 독감 바이러스 원인 300000-500, 000 명 전세계 모든 년1계산 합니다. 현재 인플루엔자 예방 및 인 간에 있는 치료에 대 한 식품의 약 청 (FDA)에 의해 승인 된 약물의 두 종류가 있다: 응집 (나) 저 해제 (예를 들어, oseltamivir) 및 차단제 (예, M2 이온 채널의 소나); 그러나, 약물 내성 바이러스 변종의 출현은 증가 한 관심사 이다. 예방 접종, 따라서 IAVs 감염 으로부터 인간을 보호 하기 위해 최상의 의료 옵션을 남아 있다. 날짜 하려면, 세 가지 유형의 독감 백신 인간의 사용을 위한 FDA에 의해 허가 사용할 수 있습니다: 재조합 형 바이러스 성 조류 (HA) 단백질 백신을 inactivated 인플루엔자 백신 (IIV), 그리고 라이브-감쇠 인플루엔자 백신 (LAIV)5, 7. 3 백신 바이러스 HA 단백질, IAVs에 대하여 항 체를 중화의 주요 대상에 대 한 적합 한 면역 반응을 유도 하도록 설계 되었습니다.
IAV 감염에서 vivo에서 공부 하는 검증 된 마우스 모델
동물 모델 공부 하 고, 다른 사람, 사이 IAV pathogenesis8,,910,11, 바이러스 성 요인 질병12 또는 바이러스 성 전송13에 기여 하는 데 사용 되었습니다. ,14,9,,1015마약 새로운 백신 또는 항 바이러스 효능을 테스트 하 고. 마우스 (생쥐)는 여러 가지 이유로 IAV 연구를 위한 가장 광범위 하 게 사용 된 동물 모델: 1) 면역 체계가 비슷합니다 진화론 인간;에 존재 하는 2) 저렴 한 비용, 등 동물 구입, 주택 및 재생산; 쉽게 조작 하 고 저장; 3) 작은 크기 균질 응답 및 결과; 4) 최소한의 호스트 가변성 5) 마우스 생물학, 게놈 시퀀스;를 포함 하 여 큰 지식 6) 많은 사용 가능한 분자 생물학 및 면역학 시 약; 7) 사용할 수 노크 바이러스 성 감염;에 주어진된 호스트 단백질의 기여 공부 하 (KO) 마우스 그리고, 8) 감염의 유전 기초를 평가 하기 위해 악용 될 수 있는 여러 마우스 긴장.
여러 마우스 긴장 IAV에서 vivo에서현재 사용할 수 있습니다. 나이, 면역 상태, 섹스, 유전 배경 및 마우스 긴장으로 감염, 복용량 및 바이러스 성 긴장의 쥐에서 IAV 감염의 결과 영향. IAV 연구에 사용 되는 가장 일반적인 마우스 긴장은 BALB/C 그리고, 최근에, DBA.2 마우스 C57BL/6, 그들은 두 전 긴장16,,1718, 보다 IAV 질병에 더 취약 19 , 20. 중요 한 것은, 면역 반응 또한 다를 수 있습니다 마우스 스트레인18,,1920에 따라. 따라서, 매우 IAV 스트레인 실시 하는 실험에 대 한 최상의 옵션을 선택 하 고 마우스에 대 한 사용 가능한 모든 정보를 복구 하는 것이 중요 하다.
마우스 IAV vivo에서 공부에 대 한 감염의 좋은 동물 모델 이지만, 그들은 실험적인 디자인에서 고려해 야 할 몇 가지 제한이 있다. 예를 들어, vivo에서 학문에 대 한 마우스를 사용 하 여의 주요 한계는 IAVs 쥐 중 전송 하지 않습니다. 따라서, 전송에 대 한 연구, 더 허용 동물 모델 (예를 들면, 흰 족제비 또는 기니 피그)는 사용된16,,1721. 또한, 쥐에서 IAV의 발현과 인간 간의 몇 가지 차이점이 있다. 인간과 달리 쥐 IAV 감염; 시 발열 개발 하지 않습니다. 반대로 그들은 저체온증16,17제시. 쥐, IAV 복제 위 항공 보다 더 낮은 호흡 기관 (폐)에 집중. 따라서, 생쥐에서 IAV의 독성은 인간에서 본을 항상 상관 하지. 전부, 장점 보다는 제한 된 단점 큽니다, 때문에 마우스 인플루엔자 바이러스 성 병 인, immunogenicity 백신과 항 바이러스 연구에 보호 효능을 평가 하는 데 사용 하는 첫 번째 동물 모델을 나타냅니다. 또한, 그것은 윤리적으로 IAV IAV 감염의 작은 동물 모델에서 이전 증거 없이 큰 동물 모델을 사용 하 여 함께 연구를 수행 허용 되지 않을 것 이다. 이 원고에서 intranasally 생쥐를 감염 하는 방법 설명 (i.n.) IAV, 심각도 및 바이러스 성 감염의 진행 상황을 모니터링 하는 방법 및 체액 성 면역 반응 및 보호 효능을 평가 하는 데 필요한 실험을 수행 하는 방법.

<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

인플루엔자 바이러스 500000 이상의 죽음 전세계1 원인과 관련 된 직접 의료 및 입원 비용 및 직장 결근2를 고려 하 고 혼자 미국에서 십억 12-14 달러의 연간 비용. 동물 모델은 바이러스 성 병 인, 호스트 병원 체 상호 작용, 면역 반응, 평가에 독감 바이러스 (IAV) 연구에 중요 한 그리고 현재 및 새로운 백신의 효능 antivirals 뿐만 아니라 접근. 마우스 유리 작은 동물 모델 때문에 그들의 면역 시스템은 진화론 인간에서 발견 비슷합니다, 그들은 유전으로 동일한 과목으로 상용 공급 업체에서 사용할 수 있습니다, 그리고 평가에 악용 될 수 있는 여러 변종이 있다 감염, 유전으로 그리고 그들은 상대적으로 저렴 하 고 조작 하기 쉬운. 기도 통해 인간 IAV 감염 정리를 마우스는 먼저 적절 한 biosafety 제약 아래 감염 IAVs와 intranasal 접종 전에 마 취. 감염 후 IAVs의 병 인 (몸 무게 손실) 병 적 상태와 사망률 (생존) 매일 모니터링 하 여 결정 됩니다. 또한, 바이러스 성 병 인도 위 (비 강 점 막) 또는 감염 된 쥐의 낮은 (폐) 호흡기 바이러스 복제를 평가 하 여 평가할 수 있습니다. IAV 감염 시 체액 응답 비-침략 적 출혈 및 이차 항 체 검출에 의해 급속 하 게 평가 될 수 분석 실험 목적 총의 존재를 검출 하거나 항 체를 중화. 여기, 우리는 일반적인 방법을 설명 intranasally 생쥐를 감염 하는 데 사용 (도)와 IAV pathogenesis, 체액 성 면역 반응 및 보호 효능 평가.

바이러스 성 병 인 쥐에서의 특성
IAV의 병 인은 병 적 상태와 사망률의 감염에 의해 발생 관련이 있습니다. 이러한 두 매개 변수 마우스에서 쉽게 계산 될 수 있습니다: IAV 병 적 이며 감염 된 쥐에 있는 몸 무게 손실과 관련 된 생존의 비율 (그림 1) 사망률을 나타낼 것 이다. 몸 무게와 IAV 감염 된 쥐에 있는 ?...

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

Influenza A Virus Studies in a Mouse Model of Infection

인플루엔자 A 바이러스 (IAVs)는 중요 한 인간의 호흡기 병원 균. IAVs pathogenicity 이해 하 고 새로운 백신 접근의 전 임상 시험 수행 인간의 생리를 흉내 낸 동물 모델은 필요. 여기, 우리가 IAV pathogenesis, 체액 성 반응과 감염 마우스 모델을 사용 하 여 백신 효능을 평가 하는 기법을 설명 합니다.

감염 마우스 모델에서 인플루엔자 A 바이러스 연구

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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28.3K 조회수.  University of Rochester School of Medicine and Dentistry. 인플루엔자 A 바이러스 (IAVs)는 중요 한 인간의 호흡기 병원 균. IAVs pathogenicity 이해 하 고 새로운 백신 접근의 전 임상 시험 수행 인간의 생리를 흉내 낸 동물 모델은 필요. 여기, 우리가 IAV pathogenesis, 체액 성 반응과 감염 마우스 모델을 사용 하 여 백신 효능을 평가 하는 기법을 설명 합니다.

비디오: 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.

사이 Synergism을 맡은 이후로 발광 생물 이미징을 사용하여 연쇄상 구균 pneumoniae</em유아 마우스에서>와 인플루엔자 바이러스

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

연구

면역학 및 감염병학

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.

인플루엔자 바이러스에 대한 높은 처리량 검출 방법

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.

키메라 마우스 모델에서 재조합 인플루엔자 백신의 비강 관리는 점막 면역을 연구하기 위해

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.

인플루엔자 A 바이러스의 핵 단백질과 마우스 MX1 단백질의 공동 면역 침전

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.

인간 인플루엔자 바이러스 감염의 Zebrafish의 모델을 사용하여 항 바이러스 약품을 화면 및 호스트 면역 세포 반응의 특성을

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.

영상 셀 상호 작용 Tracheal 점 막에서 2 광자 Intravital 현미경 검사 법을 사용 하 여 인플루엔자 바이러스 감염 중

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.

뎅기열 바이러스 유발 급성 바이러스 뇌염 같은 질병의 뮤린 모델

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.

루시퍼라제-형광 리포터 인플루엔자 바이러스 감염 의 실시간 이미징 및 정량화

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.

인플루엔자 A 바이러스 감염 중 T 여포 도우미 세포 및 발아 센터 반응 평가

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.

바이러스 동시 감염 시 콜로니자에서 병원체로 Streptococcus pneumoniae 의 전환을 위한 마우스 모델은 연령 악화 질병을 요약합니다.

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