專(zhuān)家論壇｜尹明：HBV感染的動(dòng)物模型研究進(jìn)展( 四 )

不清楚造成HBV嚴(yán)格種屬特異性的原因，因而HBV動(dòng)物模型都存在各自的優(yōu)勢(shì)和不足。盡管如此，這些模型可以部分模擬HBV感染患者的特征，合理的選擇這些模型，將有助于加快藥篩進(jìn)程、驗(yàn)證新療法和更快解決HBV生物學(xué)發(fā)病機(jī)制等方面的問(wèn)題。由于HBV發(fā)病機(jī)制的復(fù)雜性，已經(jīng)有研究表明，宿主因素影響HBV的感染。如許多基因(如HLA和IL-4)的遺傳多態(tài)性會(huì)影響抗原呈遞或細(xì)胞因子的產(chǎn)生，從而影響抗體的產(chǎn)生，導(dǎo)致對(duì)疫苗接種的反應(yīng)程度不同。 NTCP的多態(tài)性可能決定HBV進(jìn)入的過(guò)程。宿主因素也可能影響先天性和適應(yīng)性免疫，包括巨噬細(xì)胞的激活和吞噬、APCs的抗原呈遞以及HBV特異性T淋巴細(xì)胞的啟動(dòng)和功能，從而影響HBV的清除和持續(xù)性。人類(lèi)相關(guān)基因的遺傳多態(tài)性可以直接或間接地決定這些免疫功能。例如，目前的人源化NTCP轉(zhuǎn)基因或者定點(diǎn)敲入KI模型，只能實(shí)現(xiàn)HDV的瞬時(shí)感染，不能實(shí)現(xiàn)HBV的感染。如果，通過(guò)人源化導(dǎo)入HBV的受體和HBV關(guān)鍵易感基因，實(shí)現(xiàn)小鼠肝細(xì)胞對(duì)HBV的易感性并產(chǎn)生cccDNA ，必將促進(jìn)HBV小鼠模型臨床前模型質(zhì)的飛躍。相信隨著研究的進(jìn)一步突破，將會(huì)有更理想的HBV臨床前模型出現(xiàn) ，為最終治愈乙型肝炎提供幫助。
參考文獻(xiàn)：
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專(zhuān)家論壇｜尹明：HBV感染的動(dòng)物模型研究進(jìn)展( 四 )

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