No description available.

Les souches humaines de rotavirus du groupe A (RVA) reconnaissent des glycannes fucosylés de la famille des Histo-Blood Group Antigens (HBGAs) et des gangliosides via la protéine de capside VP8*. L’interaction avec les gangliosides est essentielle pour l’entrée cellulaire et l’absence de ligands fucosylés dû au polymorphisme génétique des HBGAs est associée à une résistance à la gastroentérite sévère. Nos objectifs étaient de délimiter la contribution des HBGAs et du ganglioside GM1a dans le processus d’infection et d’explorer les conséquences du polymorphisme des HBGAs sur la transmission du virus et l’efficacité des vaccins vivants disponibles.génoty Ces travaux ont permis de montrer la concordance entre la spécificité glycannique des VP8* P[8], génotype le plus fréquent en France, et la sensibilité HBGA-dépendante à la gastroentérite sévère. La reconnaissance des HBGAs par les souches humaines de RVA apparaît donc essentielle pour l’infection symptomatique. Néanmoins, nos résultats suggèrent que l’attachement aux HBGAs correspond à un événement précoce puisqu’il n’est pas nécessaire pour l’infection de cellules peu différenciées par les souches P[8] adaptées à la culture. La contribution du GM1a dans l’infection reste incertaine. Enfin, nous avons montré que la reconnaissance des HBGAs est conservée entre des souches P[8] récentes et anciennes, indiquant que le polymorphisme des HBGAs pourrait contribuer à expliquer le défaut d’efficacité des vaccins dans les régions où la fréquence d’individus n’exprimant pas les ligands fucosylés est élevée. / Human strains of rotavirus A (RVAs) recognize fucosylated glycans of the histo-blood group family (HBGAs) as well as gangliosides through the VP8* protein of their capsid. Interaction with gangliosides is essential for cell entry and lack of fucosylated ligands due to HBGAs genetic polymorphism is associated with resistance to RVA gastroenteritis. Our goals are to delineate the contribution of HBGAs and gangliosides in the infection process and to explore the consequences of HBGAs polymorphisms on the virus transmission and efficacy of the available live vaccines. This study highlighted the concordance between the glycan specificity of P[8] VP8*, the most common genotype in France, and the HBGA-dependant susceptibility to RVA gastroenteritis. The recognition of HBGAs by human RVA strains therefore appears essential to the infection. Yet, our results suggest that HBGA binding corresponds to an early event since it is not required for infection of poorly differentiated cells by cell culture-adapted P[8] strains. The contribution of GM1a on infection remains unclear. Finally, we showed that HBGA recognition is conserved between recent and older P[8] strains, suggesting that HBGAs polymorphism may contribute to explain the low efficacy of vaccines in areas where the frequency of individuals who do not express fucosylated ligands is high.

Chlamydiae are obligate intracellular pathogens that cause several serious conditions within the human host. Many of the symptoms associated with infection are thought to stem from the development of aberrant, or persistent, chlamydiae. Factors leading to chlamydial persistence include deprivation of amino acids, the release of certain cellular factors, or the addition of inhibitors of bacterial cell wall or DNA synthesis. Such changes within the chlamydial environment often lead to modifications in cell morphology, gene expression, chlamydial development, and antigen localization. In this report, I examine changes in antigen production and localization in Chlamydia-infected cells cultured in the presence of environmental stressors. There are three major areas of chlamydial biology examined: 1) how do the chlamydiae divide in the absence of FtsZ, 2) what is the importance of the predicted peptidoglycan hydrolase, PapQ; 3) what changes occur in antigen production and localization during the development of chlamydial persistence. One significant nonproteinacious factor apparently involved in chlamydial division is the SEP (septum) antigen, which localizes to the midcell of dividing chlamydiae. Non-dividing forms, such as persistent chlamydiae and EB, lack the septal placement of SEP, further suggesting the involvement of SEP in RB division. The production of the predicted hydrolase, PapQ, localizes to the cytosol of RB and, to a limited extent, within the EB. PapQ begins to accumulate as early as 12 hours after infection and during the time of RB-EB transition, an additional, smaller PapQ product accumulates. Ampicillin and tetracycline treatment inhibits accumulation of the smaller product suggesting that PapQ may be processed by a late expressed protease. This may have significance in RB-EB transition. The IncA-laden fibers protruding from the inclusion and into the host cytosol colocalize with a variety of different antigens that are generally restricted to the chlamydial outer membrane. Changes in culture conditions leads to changes in the amount and type of antigens localizing within the fibers. Chlamydial persistence dramatically influences the production and localization of several chlamydial antigens, creating significant changes in chlamydial cell biology that may enhance survival within the host. / Graduation date: 2003

Thesis (M.S.)--University of Delaware, 2006. / Principal faculty advisor: Daniel T. Simmons, Dept. of Biological Sciences. Includes bibliographical references.

published_or_final_version / Pathology / Master / Master of Philosophy

Although several risk factors for severe influenza infection have been identified in previous studies, many patients having multiple risk factors only developed mild symptoms while many healthy young patients developed severe complications when infected with A(H1N1)pdm09. Thus, there are still undiscovered factors that affect the progression and severity of influenza. The early innate immune response may be critical in determining the disease progression. Non-neutralizing antibodies existed in the early stage of infection may contribute to the outcome of the disease. In this study, the association of disease severity with the titre and avidity of non-neutralizing antibodies in early stage of influenza infection was investigated. It has been shown that the titre of non-neutralizing antibody was higher in more severe patients in the early stage of infection. Higher antibody avidity was also found to be associated with more severe disease independently. These findings tend to support the view that antigenic drift leads to an excessive production of pro-inflammatory non-neutralizing antibodies in the patients and associated with severe outcome. Since patients with more severe disease tend to have a delayed clearance of the virus and allow more transmission, the antigenically shifted or drifted influenza virus may gradually become predominant in human population. This idea suggested that the predominance of influenza virus with NA-H275Y mutation in 2007-2008 was contributed by the co-existing, fitness restoring secondary adaptive mutation in HA. NA-H275Y was identified in previous studies to be the mutation encoding for the influenza virus to resist against oseltamivir but would also change the property of NA as a result of compromised viral fitness. Therefore, influenza virus carrying NA-H275Y is unlikely to emerge and spread in human population. However, NA-H275Y mutated strains of influenza virus emerged and spread globally in the influenza season of 2007-2008 and quickly become the predominant strain in 2008. Previous study found NA-R222Q and NA-V234M were the mutations responsible for restoring the viral fitness in oseltamivir resistant clinical isolates. Still, this cannot fully explain the predominance of the resistant strains over the susceptible strains. Therefore secondary adaptive mutation in HA was believed to be present and cause antigenic change to the resistant strains of influenza. In this study, mutual information analysis and HA structural analysis were conducted to screen out HA-A189T and HA-Y94H to be the candidates co-exist with NA-H275Y and possibly critical for antigenic changes. This study further suggested that HA-Y94H mutation leads to a change of antigenic property of the virus by examining the antigenicity and growth kinetics of the recombinant viruses carrying the selected HA mutations. HA-94 may be critical for determining both the receptor binding property and antigenic property of the virus. Review on the evolution of seasonal influenza viruses from 2005 to 2008 suggested that the emergence of HA-Y94H mutation may enhance the presence of NA-H275Y and helps the viruses carrying NA-H275Y to spread and dominate over the oseltamivir susceptible strains during 2007 and 2008. / published_or_final_version / Microbiology / Master / Master of Philosophy

No description available.

published_or_final_version / Zoology / Master / Master of Philosophy

published_or_final_version / Zoology / Master / Master of Philosophy

published_or_final_version / Zoology / Master / Master of Philosophy