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Sylvia Reemers

Monday 10 May 2010

Transcriptomics of host-virus interactions: Immune responses to avian influenza virus in chicken

Promotor: Prof.dr W. van Eden
Defence: 5 May 2010
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Summary
Upon entry of the respiratory tract avian influenza virus (AIV) triggers early immune responses in the host that are aimed to prevent or control infection. Although much research is performed to elucidate the course of events that follow after AIV infection, the interactions between the virus and the host at molecular level at an early stage of infection are unclear. More insight in the mechanisms underlying innate and adaptive immune responses leading to pathogenesis or elimination of the AIV may contribute to a better understanding of AIV induced pathogenesis and new concepts for vaccine development. In this thesis we unravelled several aspects of early host responses after primary AIV infection and viral challenge in immunised chickens at host transcriptional level. The use of genome-wide microarray analysis in combination with more classical techniques allowed us to elucidate possible correlates of protection or pathogenesis at cellular and transcriptional level.

Early host responses to respiratory virus infections are complex processes providing the first defense against AIV infection and are influenced by various factors. The research into host responses is influenced by the sampling method, because airflow and anatomy affect virus distribution in the lung enhancing differences in host responses between different segments in the lung already seen in uninfected birds. This points out the importance of sampling approach which has to be taken into account when investigating in vivo responses to respiratory virus infections in large organs. Host responses themselves are directly affected by the age and adjuvants. Prolonged and enhanced responses relate to the maturation of the respiratory immune system and may be key factors in age-dependent susceptibility to infection and induction of protective responses. A high neutralizing antibody titer is a known correlate of a protective response. This correlate of protection relates to lower gene expression levels and less cellular influxes indicating that a lack of immune activation is the most important correlate of protection after AIV challenge. The findings presented in this thesis enhance our knowledge on the course of events that follow early after AIV infection leading to pathogenesis or elimination of AIV.

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