Luo T, Douglas J L, Livingston R L, Garcia J V
Department of Virology and Molecular Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Virology. 1998 Feb 15;241(2):224-33. doi: 10.1006/viro.1997.8966.
Retroviruses have been extensively used in the development of gene transfer systems. Recently, there has been a great deal of interest in the use of lentiviruses for gene transfer because they infect nondividing cells. Human immunodeficiency virus (HIV) has been the lentivirus most often used for this purpose, but its genomic complexity and limited tropism present some challenges to the establishment of efficient gene transfer systems. In this paper we present data showing intrinsic differences between the infectivity of wild-type HIV and HIV particles pseudotyped with heterologous envelope glycoproteins. Interestingly, HIV pseudotypes with envelope glycoproteins from the amphotropic murine leukemia virus or the vesicular stomatitis virus (VSV) are 3 and 40 times more infectious than wild-type HIV, respectively. In addition, we show that the reliance on Nef expression for maximal infectivity of HIV particles is dependent on the path of virus entry. The dependence on Nef for higher infectivity is greater for amphotropic pseudotypes and wild-type HIV than for VSV-G pseudotypes. We conclude that VSV-G pseudotypes of HIV vectors are an excellent choice for gene transfer purposes and Nef-mediated viral infectivity enhancement is affected by virus entry pathway.
逆转录病毒已被广泛用于基因转移系统的开发。最近，人们对使用慢病毒进行基因转移产生了浓厚兴趣，因为它们能感染非分裂细胞。人类免疫缺陷病毒（HIV）是最常被用于此目的的慢病毒，但其基因组复杂性和有限的嗜性给高效基因转移系统的建立带来了一些挑战。在本文中，我们展示的数据表明野生型HIV与用异源包膜糖蛋白假型化的HIV颗粒的感染性存在内在差异。有趣的是，具有嗜异性鼠白血病病毒或水疱性口炎病毒（VSV）包膜糖蛋白的HIV假型分别比野生型HIV的感染性高3倍和40倍。此外，我们表明HIV颗粒最大感染性对Nef表达的依赖性取决于病毒进入途径。嗜异性假型和野生型HIV对Nef的更高感染性依赖性比对VSV-G假型更大。我们得出结论，HIV载体的VSV-G假型是基因转移目的的极佳选择，并且Nef介导的病毒感染性增强受病毒进入途径影响。
