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Avian influenza A viral genetic determinants of cytokine hyper-induction in primary human macrophagesMok, Ka-pun, Chris. January 2009 (has links)
Thesis (Ph. D.)--University of Hong Kong, 2010. / Includes bibliographical references (leaves 171-213). Also available in print.
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Optimization of detection of avian influenza virus in formalin fixed tissues by immunohistochemical methodsWong, Pik-wa, Linda., 黃碧華. January 2009 (has links)
published_or_final_version / Pathology / Master / Master of Medical Sciences
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Epidemiology of avian influenza Type A viruses with specific emphasis on H9N2 in PakistanChaudhry, Mamoona January 2013 (has links)
This thesis examines the epidemiology of avian influenza viruses (AIVs) in domestic poultry in Pakistan. Major aim of the current research was: to identify risk factors associated with the spread of these viruses; to quantify their prevalence in live bird retail stalls (LBRSs) and backyard poultry in Lahore district and to genetically characterize AIVs circulating in these stalls. Four independent studies were conducted which included (i) a retrospective matched case-control study in commercial poultry farms in Pakistan to identify the risk factors (ii) an estimation of the seroprevalence of AI from a cross-sectional study of backyard poultry flocks in Lahore district (iii) a cross-sectional study of LBRSs to estimate virus prevalence and identify associated risk factors and (iv) the genetic characterization of isolates collected from LBRSs. The retrospective matched case-control study identified five risk factors for AI infection. Multivariate conditional logistic regression model showed that distance of less than 0.5 kilometer of a commercial farm from the nearest case farm (OR= 145.4; 95% CI: 13.6-1553.5), followed by “previous history of infection of flock with infectious bursal disease (OR= 3.77; 95% CI: 1.18-11.97)”, selling of birds/eggs directly to live bird retail stalls from the farm premises (OR= 9.5; 95% CI: 1.7-51.9) have significant influence on spread of AI infection amongst the commercial farms. Other significant potential risk factors are “age of flock at the time of testing (OR= 1.0; 95% CI: 1.00-1.02)” and “a truck entering the farm areas (OR= 30.74; 95% CI: 1.56-604.78)”. Complete fencing of the farm was observed to be a protective factor (OR= 0.12; 95% CI: 0.02-0.63). The cross-sectional survey of backyard poultry flocks for AI (H9, H7 and H5) showed a seroprevalence of 67% (95% CI: 56.9-77.1) for H9 and 21% (95% CI: 13.8-28.1) for H5. Co-infection with both H9 and H5 was observed in 17 villages. Seroprevalence for H9 was significantly associated with the breed of bird. No samples were positive for H7. The cross-sectional survey of LBRSs in 07 towns of Lahore district showed the prevalence of H9N2 virus to be estimated at 10% (95% CI: 6.4-13.6). Subtypes H5N1 and H7N3 were not detected in any sample. Three risk factors showed a strong association with prevalence of H9N2 which are “adding new birds to the cages that already contained birds (OR= 9.2; 95% CI: 2.4-35.1)”, “purchasing birds for sale on the stall from mixed sources (other live poultry markets, auction markets, farm/individual producers) (OR= 3.4; CI 95%: 1.3-8.8)”, and “keeping birds partially inside and outside on the stalls during the day (OR= 1.7; CI 95%: 1.0-3.0)”. Phylogenetic analysis of ten H9N2 viruses isolated from LBRSs of Lahore district showed that four genes (HA, NA, M and NP) of all viruses belonged to G1-lineage and clustered with A/Quail/Hong Kong/G1/97 reference virus while the other four genes (PB2, PB1, NP and NS) from two of the viruses analysed clustered with a group of viruses from Indian subcontinent, Persian Gulf and Middle East. One recently reported H7N3 isolate from Pakistan also clustered with these genes. All H9N2 viruses examined harboured the mutation known to alter the receptor binding profile to one that preferentially binds to human receptors. The analysis shown in this study confirmed that further gene assortment has occurred since its emergence in poultry in Pakistan and Middle East, which could evolve into new genotype. Understanding the epidemiology of avian influenza has always been considered important in formulating and implementing control policies. Results from the current studies illuminate various aspects of epidemiological features of avian influenza viruses within poultry marketing systems in Asia. The current thesis has identified different risk factors and has also reported the prevalence estimates in backyard birds and LBRSs. The presence of reassortants of H9N2 with public health importance in LBRSs has also been reported in the current thesis. These results could be considered to plan future research and appropriate control and prevention strategiess for AIV by the global community. Continued surveillance and monitoring is essential to identify the viral gene pool circulating in live bird retail stalls and backyard poultry and to better understand the public-health risk posed by these viruses.
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Molecular detection and identification of avian influenza viruses by cDNA microarrayMaughan, Michele Nancy. January 2007 (has links)
Thesis (M.S.)--University of Delaware, 2006. / Principal faculty advisor: Calvin L. Keeler, Dept. of Animal & Food Sciences. Includes bibliographical references.
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Genesis and evolution of H6N1 virus in terrestrial poultry in southernChinaCheung, Chung-lam., 張仲林. January 2011 (has links)
During the 1997 Hong Kong ‘bird flu’ incident, three subtypes of influenza
viruses, including H5N1, H9N2 and H6N1, were co-circulated at the live-poultry markets. Genetic analyses revealed that all these viruses shared the same internal gene complex and might have been all involved in generation of the HK/97-like H5N1 virus. Subsequent epidemiological and genetic studies found that both H6N1 and H9N2 viruses became established and prevalent in minor poultry in the region. However, the genesis pathway for each of these viruses has not been defined. It is also unclear about these three subtypes further interact with each other and evolve in the field, along with the emerging reassortant variants.
To address these questions, H6 subtype of avian influenza viruses isolated
from terrestrial minor poultry from 2000 to 2005, and from 2006 to 2007 in our
influenza surveillance in southern china has been genetically and antigenically
analyzed in this study. Genetic and phylogenetic analyses of representative strains indicated that all H6N1 isolates from 2000 to 2007 had W312-like hemagglutinin and neuraminidase genes. These H6N1 viruses have become established in the minor poultry, mainly in quail and chukar, in this region. However, phylogenetic analyses revealed that the internal genes of the H6N1 virus lineage were derived from multiple origins with different evolutionary pathways. Evolution analyses of different gene segments of H6N1 viruses revealed imbalance dynamic evolutionary rates between surface genes and internal genes, which suggests that this virus lineage was more likely a descendant of the HK/97-like H5N1, rather than its precursor virus.
Similar to what have been observed in the H5N1 and H9N2 virus lineages, the
internal gene complex of the H6N1 viruses was found to undergo extensive
reassortment. Many novel internal gene segments of H6N1 viruses were first
recognized in the reassortant H9N2 virus particles, suggesting that the gene flow is likely from H9N2 to H6N1. The co-circulation of different virus lineages in southern China has greatly increased the genetic diversity of influenza viruses in this region. Analyses of the dynamics of different H6N1 reassortant variants also showed that some of them became persistent, but others were transient in the field. The increasingly diversified H6N1 and other subtypes of viruses will naturally increase the opportunity of interspecies transmission and dissemination, and may pose renewal threat for public health. / published_or_final_version / Microbiology / Doctoral / Doctor of Philosophy
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Identification and evaluation of protective activity of a T cell epitope targeting nucleoprotein of H5N1 influenza virusCao, Tingting., 曹婷婷. January 2012 (has links)
The outbreaks of human influenza caused by highly pathogenic avian influenza
H5N1 virus have attracted a lot of attention and public concern. Effective and
universal vaccines may be the best means for prevention and control of the influenza.
Taking into account that viral clearance and recovery from influenza A virus infection
have been demonstrated to be correlated to specific cytoxic T lymphocyte (CTL)
instead of neutralizing antibodies, it is important to develop effective vaccines which
are capable of inducing not only neutralizing antibody but also CTL responses.
Furthermore, T cell epitopes are usually more conserved than neutralizing epitopes.
However, rare information concerning human T cell epitopes specific to H5N1 virus
has been reported so far.
This study was designed to test our hypothesis that novel and potent human CTL and
Th epitopes specific to NP protein of H5N1 virus may be identified in vaccinated
and/or infected HLA-A2/DR1 transgenic mice (SURE/L1), while protective epitopes
may be further defined from the identified T cell epitopes in the mice challenged with
lethal dose of the virus. We used SURE/L1 mouse model because it contains HLA-A2
(*0201) and -DR1 (*0701), both are the second highest frequency of HLA class I and
II in Chinese. Since the NP gene is relatively conserved among different clades or
strains of H5N1 virus, we selected viral protein NP as the target. Furthermore, we
screened the T cell epitopes in splenocytes not only from vaccinated mice but also
from survived mice infected with gradually increased dose of H5N1 virus, because
the T cell epitopes identified in both vaccinated and infected mice or in infected mice
alone might have higher potential to be protective epitopes.
In this study, a novel HLA-DR1 (class II) restricted T cell epitope NP368-382, NPII-7,
was identified in both vaccinated and infected mice. Two doses of NPII-7 peptide
boosting in the mice induced very strong Th1 and CTL responses but no NP specific
antibody responses. The vaccination of additional 2 doses of NPII-7 also provided
partial protection against lethal challenge of H5N1 virus in the mice, whereas NP
DNA vaccination alone did not show any protective effect. The protective effect may
be attributed to the strong Th1 and CTL responses induced by the NPII-7 vaccination,
because both NP DNA and NPII-7 vaccinations could not induce neutralizing
antibody response.
Notably, a HLA class II restricted peptide, NPII-7, may induce not only Th1
responses but also more strong HLA class I restricted T cell (CTL) responses. It may
probably due to that the HLA-DR1 restricted T cell epitope
(NENMEAMDSNTLELR) contained the full sequence of a reported HLA-A2
restricted CTL epitope (AMDSNTLEL), named NP-17 in this study. Although it
needs to be further defined whether this novel epitope is really a HLA-DR1 restricted
T cell epitope, or it shares the activity of HLA-A2 restricted T cell epitope, or it is
just an alternate HLA-A2 restricted T cell epitope, this study has identified a novel T
cell epitope and proved that it is a protective T cell epitope. / published_or_final_version / Microbiology / Master / Master of Philosophy
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Characterizations of antigenic and receptor binding properties of avian H5N1 and 2009 pandemic H1N1 virusesLau, Siu-ying., 劉韶瑩. January 2011 (has links)
Avian H5N1 viruses have perpetuated in poultry and caused sporadic human transmission since 1997. Vaccine candidates for the potential pandemic caused by H5N1 viruses have been continuously updated by World Health Organization. Multiple genetic lineages of H5N1 viruses which co-circulate and rapidly evolve in different regions, together with periodic population replacement of newly emerged genetic and antigenic variants in the field, pose great challenge for H5N1 vaccine candidate selection. The complexity of avian H5N1 viruses evolution raises an important issue for studying antigenic properties and also for projecting antigenic trend of this virus since the model established for the seasonal influenza viruses may not apply to H5N1 viruses which they are still in the animal phase. In contrast, the 2009 pandemic H1N1 viruses have established as another seasonal influenza viruses in humans. How will this swine originated viruses evolve genetically and antigenically in humans? For the first in human history, we are able to track the changes of pandemic viruses from the very beginning when they transmitted to human.
This study focuses on antigenic and receptor binding properties of avian
H5N1 viruses from 1997 to 2010 and 2009 pandemic H1N1 viruses from 2009 to 2011. It is found that avian H5N1 viruses continue to display highly diverse antigenic profile. The newly emerged H5N1 virus variants of clade 2.3.4 in 2008 and clade 2.3.2 in 2010 exhibit distinct antigenic properties as compared to the genetically similar viruses that were characterized previously. Receptor binding analysis showed H5N1 viruses still exhibit binding preference for avian type receptor. However, analysis of escape mutants selected from H5N1 viruses exposed to H5 monoclonal antibodies in cell based assay indicates that mutations in the conserved sites may cause switch of receptor binding specificity to human type or dual specificity for both human and avian.
Based on antigenic and receptor binding analyses, it is found that the 2009 pandemic H1N1 viruses isolated from 2009 to 2011 are relatively stable. Most of the antigenic variants to monoclonal antibodies are transient and not able to become prevalent. It remains to be investigated if more significant antigenic variants may emerge in the coming seasons when population immunity prevails this virus.
In conclusion, this study showed that clade 2.3 avian H5N1 viruses become increasingly antigenic distinct as compared to clade 2.1 and 2.2 viruses. Antigenic variation in antigenic sites may change receptor binding specificity in avian H5N1 viruses. The 2009 pandemic H1N1 viruses remain stable up to date but continue monitoring in coming seasons is necessary. / published_or_final_version / Microbiology / Master / Master of Philosophy
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Application of multiplex branched DNA method for the detection and study of avian inlfuenza [i.e. influenza] virusCha, Wonhee, January 2008 (has links)
Thesis (M. S.)--Ohio State University, 2008. / Title from first page of PDF file. Includes bibliographical references (p. 89-103).
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Development and evaluation of DNA vaccines in chickens against a wild bird H6N2 avian influenza virus from Western Australia /Shan, Songhua. January 2009 (has links)
Thesis (Ph.D.)--Murdoch University, 2009. / Thesis submitted to the Faculty of Health Sciences. Includes bibliographical references (p. 275-332)
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Mechanisms of pathogenic avian influenza-induced immune responses in human cellsMok, Ka-pun, Chris. January 2004 (has links)
Thesis (M. Phil.)--University of Hong Kong, 2005. / Title proper from title frame. Also available in printed format.
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