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Title: Pathogenesis and genetic markers for virulence of highly pathogenic avian influenza (HPA1) H5N1 virus
Author: Löndt, Brandon Zach
ISNI:       0000 0004 2716 8583
Awarding Body: University of Reading
Current Institution: University of Reading
Date of Award: 2011
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A variety of factors are thought to contribute to the pathogenesis of avian influenza (AI) viruses. Three of these factors: host, immunity and virus strain, were studied. Specifically, tissue tropism in hosts usually regarded as resistant to infection with HP AI viruses; the effect of prior immunity on infection; the effect of age on disease outcome and the genetic factors of the virus were studied. The ability of "Asian- lineage" A/turkey/Turkeyll/2005 (H5Nl) HPAI virus (clade 2.2) virus to produce disease and mortality in Pekin ducks was affected by the age at infection. In 4- week-old Pekin ducks, infection resulted in systemic infection, severe neurological signs and 100% mortality. Viral shedding was primarily from the oropharyngeal route. Only mild clinical signs and no mortality was observed in 12-week-old ducks infected with the same dose of this virus. Clinical signs and mortality rates in 8- week-old ducks were similar to those observed in 4-week-old ducks, but viral shedding and virus loads in tissues were shown to be lower, and generally absent in brain and heart tissues in both age groups of older ducks. Prior infection of 3-week- old ducks with a low pathogenicity AI (LP AI) H5N2 virus and subsequent challenge at 7- and 16-weeks-old with A/turkey/Turkey/1/2005 HPAI H5Nl was shown to decrease the severity of clinical signs and the amount of virus shed, although in this particular study mortality was observed in neither prior infected or naive birds on challenge. Viral genetic markers for virulence of HP AI viruses in chickens were studied in two genetically similar HP AI H5Nl viral clones - A/turkey/England/50-92/l 991 2L and A/turkey/England/87-9211991 LDP3, which displayed high and low virulence in intravenous pathogenicity (IVPI) tests with indices of 1.77 and 0 respectively. Ten amino acid differences in five genes - PB1, PB2, PA, HA and NP, were identified between these two isolates. Nine of these differences, the exception being the one in the NP gene, were shown to contribute to the high virulence of the 2L clone since they were induced in the low virulence LDP3 clone after intracerebral passage in day-old chicks and led to a change in phenotype to a high IVPI score. Two mutations in PBl unique to LDP3, located in a known functional domain involved in the binding ofPBl to both PB2 and vRNA, were shown to reduce 2L polymerase function significantly in chicken cells when measured by an in vitro polymerase activity assay. This finding highlights the important contribution of polymerase function to the virulence of AI viruses. The results from the present study collectively highlight the complex polygenic nature of HP AI virus infections in avian hosts.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available