Human immunodeficiency virus type 1-derived lentivirus vectors pseudotyped with envelope glycoproteins derived from ross river virus and semliki forest virus

Human immunodeficiency virus type 1-derived lentivirus vectors pseudotyped with envelope glycoproteins derived from ross river virus and semliki forest virus
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DOI:
10.1128/jvi.78.3.1421-1430.2004
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发表时间:
2004-02-01
影响因子:
5.4
通讯作者:
Cornetta, K
Cornetta, K
中科院分区:
医学2区
文献类型:
--
作者:
Kahl, CA;Marsh, J;Cornetta, K

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罗斯河病毒(RRV)和塞姆利基森林病毒(SFV)是两种氨基酸同源性很高、宿主范围非常广泛的甲型病毒。我们在这里表明,来自这两种病毒的包膜糖蛋白可以伪型人类免疫缺陷病毒1型(HIV-1)衍生的慢病毒载体。RRV和SFV糖蛋白都极大地扩大了慢病毒载体的宿主范围,通过超速离心法可以有效地浓缩载体。对甲型病毒糖蛋白和水疱性口炎病毒糖蛋白(VSV-G)的系统分析表明,慢病毒载体携带RRV糖蛋白的效率与VSV-G相当。两种伪型的物理滴度具有可比性,但RRV伪型的感染性滴度低于VSV-G。将SFV糖蛋白掺入慢病毒载体的效率较低,导致物理滴度和感染性滴度降低。使用聚乙二烯和包被CH-296重组纤维连接蛋白片段的平板,可以显著提高VSV-G-、RRV-和SFV-伪型慢病毒载体对贴壁细胞的转导效率。综上所述,我们的数据表明RRV和SFV糖蛋白可能适合作为VSV-G的伪分型慢病毒载体的替代品。
Ross River virus (RRV) and Semliki Forest virus (SFV) are two alphaviruses that have a high degree of amino acid homology, as well as a very broad host range. We show here that envelope glycoproteins derived from both viruses can pseudotype human immunodeficiency virus type 1 (HIV-1)-derived lentivirus vectors. Both RRV and SFV glycoproteins considerably expand the host range of the lentivirus vector, and vectors can be efficiently concentrated by ultracentrifugation. A systematic analysis comparing the alphaviral glycoproteins to the vesicular stomatitis virus glycoprotein (VSV-G) revealed that lentivirus vectors incorporate RRV glycoproteins with an efficiency comparable to that of VSV-G. Both pseudotypes have comparable physical titers, but infectious titers with the RRV pseudotype are lower than with VSV-G. Incorporation of SFV glycoproteins into lentivirus vector is less efficient, leading to decreased physical and infectious titers. The transduction rates with VSV-G-, RRV-, and SFV-pseudotyped lentivirus vectors into adherent cell lines can be significantly increased by using a combination of Polybrene and plates coated with CH-296 recombinant fibronectin fragments. Together, our data suggest that RRV and SFV glycoproteins might be suitable as alternatives to VSV-G for pseudotyping lentivirus vectors.