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KMID : 0882420050690040357
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Korean Journal of Medicine
2005 Volume.69 No. 4 p.357 ~ p.363
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The significance of pre-S1 mutants as a cause of groundglass hepatocyte during HBV infection
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조용균:Cho Yong-Kyun
김병익:Kim Byung-Ik/배지철:Pae Ji-Cheul/박승하:Park Seung-Ha/김상훈:Kim Sang-Hoon/박정호:Park Jung-Ho/김홍주:Kim Hong-Joo/박동일:Park Dong-Il/김향:Kim Hyang/성인경:Sung In-Kyung/손정일:Sohn Chong-Il/전우규:Jeon Woo-Kyu
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Abstract
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‘Background : Groun glass hepatocytes are wique Histologial feature of chronic hepatits B viral
infection. The pre-S1 region of large surface protein has been shown (o regulate assembly,
processing, and secretion of HBsAg. The purpose of this study was (o clucidate that a mutant form
of pre-S1 alfects this norml secretory pathway and is responsibe for ground glass hepatocyte.
Methods : We examined HBV sequences spanving the pre-S region from a patients with HBeAg
positive chronic HBV infection. HBV DNA was extracted from serum, cloned, and sequenced and
determined the inrahepatic viral composition by extracting HBV DNA from paralfin embedded lver
tissue. To anayze the virl popalation of single groundelass heptocytes, we used the technique of
Laser capture microdissection to isolate individual hepatocytes from biopsy specimen. Groundglass
hepatocyles that stained postively with anti-HBs and normal hepatocytes were harvested
indivicuall and their subjected HBV DNA sequences were analyzed. To define the responsible
mutations for the HBsAg secreton, we introduced the mutant gone into molecular clone of wikliype
(adwR9) and assayed their HBsAg amounts in the transfected cell supernatants by ELISA.
Reaults : Of 12 clones in serum analyzed, 9 clones had identical wild type sequences in the
N-terminal region of he pre-S1 protein Which plays an important role in the secreton and retention
of HBY envelope proteins. One of the wid type clones has deleton within pre-S2 region. 3 iertical
mutant clones were isolsted. Mutant type clones were predominant groundelass hepstocytes.
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