Infectivity determinants of the hepatitis B virus pre-S domain are confined to the N-terminal 75 amino acid residues
Infectivity determinants of the hepatitis B virus pre-S domain are confined to the N-terminal 75 amino acid residues
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DOI：
10.1128/jvi.00096-07
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发表时间：
2007-06-01
影响因子：
5.4
通讯作者：
Sureau, Camille
中科院分区：
文献类型：
--
作者：
Blanchet, Matthieu;Sureau, Camille
B肝炎病毒（HBV）大包膜蛋白N端前S区在病毒进入途径的起始阶段起着关键作用。在本研究中，整个前S结构域映射的感染性决定因素，以下反向遗传学的方法，并使用体外感染试验与丁型肝炎病毒（HDV）或HBV颗粒。结果表明，在前S区的N-末端75个氨基酸内产生的损伤消除了感染性，而与基质结构域重叠的氨基酸76和113之间的突变没有影响。与最近的一项研究结果相反（L。Stoeckl，A. Funk，A. Kopitzki，B.勃兰登堡，S. Oess，H.威尔，H。Sirma和E. Hildt，Proc. Natl. Acad. Sci. 103：6730-6734，2006），位于pre-S2的C末端的氨基酸148和161之间的细胞膜易位基序（TLM）的缺失不干扰所得HDV或HBV突变体的感染性。此外，一系列与前S2结构域重叠的大缺失与感染性相容，尽管当缺失延伸到前S1结构域时感染效率降低。总体而言，结果表明，前S结构域在病毒进入时的活性仅取决于其前75个氨基酸的完整性，因此排除了基质结构域或TLM的任何功能。
The N-terminal pre-S domain of the large hepatitis B virus (HBV) envelope protein plays a pivotal role at the initial step of the viral entry pathway. In the present study, the entire pre-S domain was mapped for infectivity determinants, following a reverse-genetics approach and using in vitro infection assays with hepatitis delta virus (HDV) or HBV particles. The results demonstrate that lesions created within the N-terminal 75 amino acids of the pre-S region abrogate infectivity, whereas mutations between amino acids 76 and 113, overlapping the matrix domain, had no effect. In contrast to the results of a recent study (L. Stoeckl, A. Funk, A. Kopitzki, B. Brandenburg, S. Oess, H. Will, H. Sirma, and E. Hildt, Proc. Natl. Acad. Sci. 103:6730-6734, 2006), the deletion of a cell membrane translocation motif (TLM) located between amino acids 148 and 161 at the C terminus of pre-S2 did not interfere with the infectivity of the resulting HDV or HBV mutants. Furthermore, a series of large deletions overlapping the pre-S2 domain were compatible with infectivity, although the efficiency of infection was reduced when the deletions extended to the pre-SI domain. Overall, the results demonstrate that the activity of the pre-S domain at viral entry solely depends on the integrity of its first 75 amino acids and thus excludes any function of the matrix domain or TLM.