细胞膜转运分子ABCC3和SLC7A7在肠道病毒A71型感染中作用的初步研究

Preliminary study on the role of membrane transport molecules ABCC3 and SLC7A7 in enterovirus A71 infection

肠道病毒A71型(enterovirus A71,EV-A71)是导致手足口病(hand-foot-mouth disease,HFMD)的主要病原体之一,目前对其治疗尚无特异高效的抗病毒药物。研究表明,细胞膜转运相关分子参与病毒的入侵、复制以及感染性子代病毒颗粒的释放。为寻找宿主中可有效抑制EV-A71感染的细胞膜转运分子,本研究以人结肠癌细胞(Caco-2)为靶细胞,采用RNA干扰技术下调细胞中14个转运相关膜蛋白的表达。结果显示,针对这14个膜蛋白目的基因设计的小干扰RNA(small interfering RNA,siRNA)均能有效抑制靶蛋白的表达,有效抑制率达50%以上(P<0.05),且各siRNA转染均未对细胞产生明显毒性。其中,转染ATP结合盒转运蛋白C3(ATP-binding cassette transport subfamily C member 3,ABCC3)siRNA(SEQ ID NO:1)和溶质载体家族7成员7(solute carrier family 7 member 7,SLC7A7)siRNA(SEQ ID NO:29)的干扰效率分别高达87.82%和88.44%。ABCC3和SLC7A7基因下调可明显抑制EV-A71的复制,抑制率分别达87.05%和81.66%。结果表明,ABCC3和SLC7A7在EV-A71感染Caco-2细胞中发挥着重要作用,可为临床EV-A71感染的预防和治疗提供潜在靶点。

Enterovirus A71(EV-A71)is one of the main pathogens causing hand-foot-mouth disease(HFMD).There are no specific and effective antiviral drugs for the treatment of HFMD.Studies have shown that cell membrane transport molecules are involved in virus invasion,replication and the release of infectious virus particles.In order to find the host factors that can effectively inhibit EV-A71 infection,human colon cancer cells(Caco-2)were used as target cells,and RNA interference was used to downregulate the expression of transport-related membrane proteins.The data showed that ATP-binding cassette transport subfamily C member 3(ABCC3)and solute carrier family 7 member 7(SLC7A7)played important roles in EV-A71 infection in Caco-2 cells,which provided potential targets for the prevention and treatment of EV-A71 infection.