Chimeric hepatitis E virus-like particle as a carrier for oral-delivery.
Chimeric hepatitis E virus-like particle as a carrier for oral-delivery.
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DOI：
10.1016/j.vaccine.2012.10.073
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发表时间：
2013-01-02
期刊：
影响因子：
5.5
通讯作者：
Cheng RH
中科院分区：
文献类型：
--
作者：
Jariyapong P;Xing L;van Houten NE;Li TC;Weerachatyanukul W;Hsieh B;Moscoso CG;Chen CC;Niikura M;Cheng RH
口服病毒样颗粒（VLP）是有利的，因为其亲本病毒衣壳的遗传进入途径，这使得VLP能够承受与人类消化道相关的恶劣和酶促环境。然而，该系统的重复使用受到自身免疫的挑战。为了解决这一问题，我们将HIV gp120 V3环衍生的p18肽插入到抗体结合位点，设计重组戊型肝炎病毒衣壳蛋白。嵌合VLP类似于野生型VLP的三级和四级结构，并与HIV抗体特异性反应。与野生型VLP不同的是，嵌合VLP虽然看起来是完整的颗粒，但很容易被胰蛋白酶切割，这表明重组衣壳蛋白之间的分子间吸引力足够强，足以维持VLP的二十面体排列。重要的是，含有V3环的VLP不与抗hev抗体发生反应，这与抗体结合位点的突变相对应。因此，在表面抗原位点插入多肽可以使VLPs逃避预先存在的抗hev体液免疫。
Oral delivery with virus-like particles (VLPs) is advantageous because of the inherited entry pathway from their parental viral capsids, which enables VLP to withstand the harsh and enzymatic environment associated with human digestive tract. However, the repeat use of this system is challenged by the self-immunity. In order to overcome this problem, we engineered the recombinant capsid protein of hepatitis E virus by inserting p18 peptide, derived from the V3 loop of HIV gp120, into the antibody-binding site. The chimeric VLP resembled the tertiary and quaternary structures of the wild type VLP and specifically reacted with an HIV antibody against V3 loop. Different from the wild type VLP, the chimeric VLP was vulnerable to trypsin cleavage although it appeared as intact particle, suggesting that the intermolecular forces of attraction between the recombinant capsid proteins are strong enough to maintain the VLP icosahedral arrangement. Importantly, this VLP containing the V3 loop did not react with anti-HEV antibodies, in correspondence to the mutation at its antibody-binding site. Therefore, the insertion of peptides at the surface antigenic site could allow VLPs to escape pre-existing anti-HEV humoral immunity.
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影响因子：
5.4
作者：
Li, TC;Takeda, N;Cheng, RH
通讯作者：
Cheng, RH
影响因子：
--
作者：
Wriggers, Willy
通讯作者：
Wriggers, Willy
DOI：
10.1124/jpet.106.107847
发表时间：
2006-11-01
影响因子：
3.5
作者：
Gullberg, Elisabet;Keita, Asa V.;Artursson, Per
通讯作者：
Artursson, Per
影响因子：
3.7
作者：
Tam AW;Smith MM;Guerra ME;Huang CC;Bradley DW;Fry KE;Reyes GR
通讯作者：
Reyes GR
影响因子：
3.1
作者：
Clark, MA;Hirst, BH;Jepson, MA
通讯作者：
Jepson, MA