Publicação
Evaluation of the 1329L as a candidate to delete for production of a viral attenuated vaccine against ASFV
| Resumo: | Viruses are obligate intracellular parasites and, as a consequence of many years of coevolution with their hosts, have evolved genes/strategies to manipulate and/or evade host cell biology and immune responses. Many of these viral evasion genes code for proteins that are non-essential for virus replication in vitro. They may, however, be considered as valuable ready made tools to extend, explore and manipulate the regulation of the basic cellular processes that they manipulate. African swine fever virus (ASFV) is a devastative acute pathogen of domestic pigs, principally in Africa where due to progressive urbanization and informal pig rearing, endemicity is growing. In its wild life hosts, both vertebrate (warthog and bush pig) and invertebrate (soft tick), however, the virus has evolved many genes to escape the full ferocity of the host immune response and is non-pathogenic. This project has focused on one such strategy, specifically, the ASFV gene I329L, which has been demonstrated to inhibit TLR signaling. Two important future possibilities have been defined by this work: 1) The demonstration that I329L is a non-essential virus gene will permit construction of an I329L deletion-mutant virus and work towards this has commenced with the successful subcloning of the flanking regions of I329L into the necessary transfer vector. The I329L deletion virus will further our understanding of the role of I329L in the pathogenesis of the ASFV infection and may justify the testing of an I329L deletion mutant as a vaccine. 2) The demonstration that I329L functions in mouse macrophages and the subsequent construction of a macrophage restricted I329L transgenic mouse will provide an in vivo system to determine the role of I329L in healthy and infected macrophages. |
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| Autores principais: | Correia, Ana Catarina Mota, 1982- |
| Assunto: | Peste Suína Africana I329L Macrófagos Receptores toll-like Evasão imune Teses de mestrado - 2009 |
| Ano: | 2009 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | Viruses are obligate intracellular parasites and, as a consequence of many years of coevolution with their hosts, have evolved genes/strategies to manipulate and/or evade host cell biology and immune responses. Many of these viral evasion genes code for proteins that are non-essential for virus replication in vitro. They may, however, be considered as valuable ready made tools to extend, explore and manipulate the regulation of the basic cellular processes that they manipulate. African swine fever virus (ASFV) is a devastative acute pathogen of domestic pigs, principally in Africa where due to progressive urbanization and informal pig rearing, endemicity is growing. In its wild life hosts, both vertebrate (warthog and bush pig) and invertebrate (soft tick), however, the virus has evolved many genes to escape the full ferocity of the host immune response and is non-pathogenic. This project has focused on one such strategy, specifically, the ASFV gene I329L, which has been demonstrated to inhibit TLR signaling. Two important future possibilities have been defined by this work: 1) The demonstration that I329L is a non-essential virus gene will permit construction of an I329L deletion-mutant virus and work towards this has commenced with the successful subcloning of the flanking regions of I329L into the necessary transfer vector. The I329L deletion virus will further our understanding of the role of I329L in the pathogenesis of the ASFV infection and may justify the testing of an I329L deletion mutant as a vaccine. 2) The demonstration that I329L functions in mouse macrophages and the subsequent construction of a macrophage restricted I329L transgenic mouse will provide an in vivo system to determine the role of I329L in healthy and infected macrophages. |
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