| Summary: | 碩士 === 國立陽明大學 === 微生物及免疫學研究所 === 97 === It is known that hepatitis delta virus (HDV) requires hepatitis B
virus (HBV) to complete its life cycle. When patients are coinfected or
superinfected with HBV and HDV, it causes fulminant hepatitis and
progressive chronic liver cirrhosis, indicating HDV plays an important
role that makes the symptoms become more seriously. The mechanism by
which HDV infection contributes to clinical hepatitis is poorly
understood. HDV has two different size of proteins, small and large delta
antigens (SDAg and LDAg), they might interact with hosts’ molecules
and make some symptoms. Our lab has established Caenorhabditis
elegans (C.elegans) as a platform to study whether HDV antigens will
affect worm growth. In previous studies, transgenic worms expressing
SDAg in pharynx caused growth retard. In my thesis, I used different
length of SDAgs named SD441, SD327, SD267, and SD201 to dissect
the domain of delta antigens, which leads to growth retard, as well the
effect of different genotypes (genotype I, genotype II, genotype III) and
expression at different stages. I found that (1) the influence are distinct in
all different length of SDAgs, except SD441, the SDAg without
nuclear-localization signal ( NLS ), (2) SDAg expression at L4 stage has
the most serious effect, and (3) the degree of effect is genotype II >
genotype I > genotype III. These results show that the entrance of SDAg
into hosts’ nucleus is very important to result in growth retardation and
egg-laying activity. SDAg might interfere with unknown molecules in the
nucleus. Therefore, if these molecules would be identified, we could
search for the homologous genes in human, and possible to delineate the
molecular mechanisms involved in the pathogenesis of HDV.
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