Kubo Yoshinao, Hayashi Hideki, Matsuyama Toshifumi, Sato Hironori, Yamamoto Naoki
Department of AIDS Research, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan ; Division of Cytokine Signaling, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan.
Adv Virol. 2012;2012:640894. doi: 10.1155/2012/640894. Epub 2012 Dec 6.
Retroviruses include infectious agents inducing severe diseases in humans and animals. In addition, retroviruses are widely used as tools to transfer genes of interest to target cells. Understanding the entry mechanism of retroviruses contributes to developments of novel therapeutic approaches against retrovirus-induced diseases and efficient exploitation of retroviral vectors. Entry of enveloped viruses into host cell cytoplasm is achieved by fusion between the viral envelope and host cell membranes at either the cell surface or intracellular vesicles. Many animal retroviruses enter host cells through endosomes and require endosome acidification. Ecotropic murine leukemia virus entry requires cathepsin proteases activated by the endosome acidification. CD4-dependent human immunodeficiency virus (HIV) infection is thought to occur via endosomes, but endosome acidification is not necessary for the entry whereas entry of CD4-independent HIVs, which are thought to be prototypes of CD4-dependent viruses, is low pH dependent. There are several controversial results on the retroviral entry pathways. Because endocytosis and endosome acidification are complicatedly controlled by cellular mechanisms, the retrovirus entry pathways may be different in different cell lines.
逆转录病毒包括可在人类和动物中引发严重疾病的感染因子。此外，逆转录病毒被广泛用作将感兴趣的基因转移到靶细胞的工具。了解逆转录病毒的进入机制有助于开发针对逆转录病毒诱导疾病的新型治疗方法，并有效利用逆转录病毒载体。包膜病毒进入宿主细胞质是通过病毒包膜与宿主细胞膜在细胞表面或细胞内囊泡处融合实现的。许多动物逆转录病毒通过内体进入宿主细胞，并需要内体酸化。嗜亲性鼠白血病病毒的进入需要由内体酸化激活的组织蛋白酶。依赖CD4的人类免疫缺陷病毒（HIV）感染被认为是通过内体发生的，但内体酸化对于进入并非必需，而不依赖CD4的HIV（被认为是依赖CD4病毒的原型）的进入则依赖低pH值。关于逆转录病毒的进入途径存在一些有争议的结果。由于内吞作用和内体酸化受到细胞机制的复杂控制，逆转录病毒的进入途径在不同细胞系中可能有所不同。
