When I first arrived in Liège, the scientific activities of our laboratory focused on the identification of candidate-genes whose different alleles interfere with the resistance/susceptibility of animals against infectious diseases. Two genes were being intensively studied (Mx and OAS) due to their theoretical potential in interfering with the replicative cycle of several viruses responsible for bovines viral pneumonias (Baise et al., 2004 ; Gerardin et al., 2004 ; Leroy et al., 2005 ; 2006). My work consisted then, in the identification of other genes potentially implicated in the resistance against the Paramyxoviruses. The Paramyxoviridae family includes some of the great and ubiquitous disease-causing viruses of animals, including the bovine parainfluenza type 3, the bovine respiratory syncytial virus, the Newcastle disease virus, the distemper virus, etc. Evidence was accumulating that genetic factors were involved both in the control of infectious diseases (Abel et al., 1991 ; 1995 ; Alcais et al., 1997 ; Jin et al., 1999 ; Martinson et al. 1997 ; Shaw et al., 1995) and in the regulation of infection levels and clinical presentation (Garcia et al., 1999 ; Plancoulaine et al., 2000 ; 2003). Thus, identifying genes that control the organism response to paramyxoviruses was a crucial step in elucidating how they might affect the pathophysiological processes underlying the severity of the disease induced. Other experiences done in this laboratory showed us how risky and difficult was any extrapolation of the mouse results to another species if these results were brought through infection with a heterologous virus, so we decided to implement this strategy with Sendai virus (SeV), the archetype organism of the Paramyxoviridae family, from which most of the basic biochemical, molecular and biologic properties of the whole family were derived from (Chanock et al., 2001). With this goal in mind my thesis was divided in five successive steps: In order to establish a standard model of SeV infection, the first step consisted in determining the best volume of inoculum that was needed to achieve a safe, reproducible pulmonary deposition of Sendai virus in the mice lungs. Secondly we developed a murine model of SeV infection using a series of different and sophisticated procedures that allowed a quantitative assessment of disease severity and progression. Then we compared SeV infections among 6 strains of mice that were deliberately chosen because they originated from different lineages, as deduced from known genealogical and phylogenetic data. Applying these procedures to distinct inbred strains of mice, revealed highly significant differences in susceptibility between them. More specifically 129/Sv were highly susceptible while BALB/c were particularly resistant, BALB/c exhibiting a benign and asymptomatic affection of the epithelium of the airways, with no functional impact, generating slight mononucleated cell infiltration, in which viral replication is repressed and the virus swiftly eliminated. As a result, in the fourth part of my study we discussed a series of hypotheses that should be tested in the future to improve our understanding of why BALB/c is so resistant to SeV infection. Practically speaking, our studies led to the gathering of a genomic DNA collection from the parental extreme lines in terms of susceptibility (129/Sv) and resistance (BALB/c) and their F1 and F2 offspring. Within this bank, each of the 263 DNA sample is associated with a portfolio of phenotypic values that are estimators of the resistance each mouse opposed to the SeV. We hope that, between expert hands, this bank will allow the detection of genes of which the alleles contribute, at least in part, to the spectacular resistance of BALB/c. The last part of my thesis consisted in applying our model to establish if the receptor TLR4 influenced the pathophysiology of the Paramyxoviridae in general. Because the role of this receptor had already been excluded for SeV, we tested another virus of the same family and homologous for the mice, the PVM (standing for pneumonia virus of mice). This work showed, in contradiction of what had been found in heterologous models in the past, that TLR4 is not involved in host defense against respiratory tract infection with the Paramyxoviridae.

The Cantell strain of Sendai virus (SeV-C) represents a typical laboratory attenuated virus which is less virulent and able to induce large amount of interferon in infected cells. This strain has widely been used in the laboratory for immunological studies due to its extraordinary ability to stimulate type I interferon production. Nevertheless, the underlying mechanism by which SeV-C is sensed by immune receptors as an invading microorganism is still largely unknown. Meanwhile, during the course of infection, Sendai virus is known to generate substantial amount of non-infectious viral particles consisting of defective interfering RNAs (DI RNAs) from replication errors. It was known that one major form of DI RNAs generated by some negative stranded RNA viruses may adopt a stem-loop panhandle structure with a relatively long double stranded region. Therefore, we hypothesized that some SeV-C DI RNAs may bear structures similar to intermediate-length dsRNA recognized by cytosolic immune receptor RIG-I, thus triggering interferon production. In this study, three DI RNAs were successfully isolated from SeV-C infected cells. Particularly, one of them designated T4 was found to contain a double stranded region of 93 base pair, and it was capable of stimulating interferon β production when transfected to reporter cells. The immunostimulatory activity of T4 alone was as potent as that of SeV-C, suggesting that T4 would be the major component in attenuated virus SeV-C that activates type I interferon production. Furthermore, cellular dsRNA binding protein PACT was shown to play a role in T4 recognition by RIG-I. T4 binds to PACT and potently stimulates PACT-induced activation of RIG-I. The identification and characterization of T4 reveals the major immunostimulatory component in SeV-C. Our work defines a RIG-I agonist naturally produced during the course of viral infection and provides a new mechanism to explain virus attenuation. We also demonstrate the role of PACT in immune sensing of a viral RNA. In addition, our findings also provide new strategies for the design and development of vaccines, vaccine adjuvants and other immunostimulatory agents. / published_or_final_version / Biochemistry / Master / Master of Philosophy

Thesis--Bonn. / Includes bibliographical references (p. 481-490).

Thesis (Ph. D.)--The University of Wisconsin--Madison, 1970. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliography.

A Thesis Submitted to the Faculty of Medicine University of the Witwatersrand, Johannesburg for the Degree of Doctor of Philosophy in Medicine Johannesburg 1986 / An investigation was done to examine the role of IFN in viral persistence at the cellular level. For this purpose two types of persistent infections were chosen. The first type was cell lines which contained hepatitis B virus (HBV) DNA (PLC/PRF/5 and Hep 3B cells) uninfected control hepatoma cells, (Mahlavu, HA22T and Hep G2 cells) or simian virus 40 (SV40) DNA (C2, C6, Cll cells) and control uninfected (CV-1 cells). In the second type of infection Vero cells persistently infected with SSPE or Sendai virus were used. / IT2018

Thesis (Ph. D.)--University of Florida, 2002. / Typescript. Vita. Includes bibliographical references (leaves 98-110).

Dissertação (mestrado)—Universidade de Brasília, Centro de Desenvolvimento Sustentável, 2017. / Submitted by Albânia Cézar de Melo (albania@bce.unb.br) on 2017-09-15T16:51:32Z No. of bitstreams: 1 2017_JomaryMauríciaLeiteSerra.pdf: 2904057 bytes, checksum: 0a7a0829c8f773e371c56c50996627ec (MD5) / Approved for entry into archive by Raquel Viana (raquelviana@bce.unb.br) on 2017-09-25T23:13:24Z (GMT) No. of bitstreams: 1 2017_JomaryMauríciaLeiteSerra.pdf: 2904057 bytes, checksum: 0a7a0829c8f773e371c56c50996627ec (MD5) / Made available in DSpace on 2017-09-25T23:13:24Z (GMT). No. of bitstreams: 1 2017_JomaryMauríciaLeiteSerra.pdf: 2904057 bytes, checksum: 0a7a0829c8f773e371c56c50996627ec (MD5) Previous issue date: 2017-09-25 / O objetivo deste trabalho é construir um diagnóstico através da avaliação do processo de gestão de risco de desastres por eventos hidrológicos no Distrito Federal. Para isso, foram consideradas as quatro ações prioritárias do Quadro de Sendai e as diretrizes da Política Nacional de Proteção e Defesa Civil. O método utilizado nesta pesquisa foi o Delphi, aplicado em duas rodadas a stakeholders envolvidos no processo de gestão do Distrito Federal e exercendo atividades ligadas a temas como recursos hídricos, meio ambiente, drenagem, planejamento territorial urbano, educação e risco de desastres. Os resultados encontrados revelaram que o Distrito Federal tem buscado trabalhar na redução dos impactos causados pelos desastres hidrológicos, contudo as ações de prevenção de riscos ainda estão abaixo do esperado, necessitando de maior compreensão do risco, investimento na redução do risco, fortalecimento da governança e melhorias na preparação para evoluir na gestão de desastres por eventos de origem hidrológica. / The objective of this research is to make a diagnosis of the Water-related hazards/disasters risk management processes in the Federal District, Brazil. In order to do this, the four priority actions of the Sendai Framework and the guidelines of the National Policy of Protection and the Civil Defense were considered. The method used in this research was the Delphi one, and it was applied two times with stakeholders involved in the local management process who carried out activities related to water resources, environment, drainage, urban territorial planning, education and disaster risk. The results revealed that the Federal District has tried to reduce the impacts caused by hydrological disasters, but risk prevention actions are still below expectations. Therefore, it is necessary to increase risk comprehension and investments in risk reduction, as well as to strengthen governance, so finally the management of disasters by events of hydrological origin could be improved.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20609号 / 医博第4258号 / 新制||医||1023(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 高橋 淳, 教授 伊佐 正, 教授 影山 龍一郎 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Stuttgart, FH, Diplomarb., 2003.

京都大学 / 0048 / 新制・課程博士 / 博士(生命科学) / 甲第20782号 / 生博第388号 / 新制||生||51(附属図書館) / 京都大学大学院生命科学研究科統合生命科学専攻 / (主査)教授 藤田 尚志, 教授 朝長 啓造, 教授 永尾 雅哉 / 学位規則第4条第1項該当 / Doctor of Philosophy in Life Sciences / Kyoto University / DFAM