Laboratory of Signal Transduction, Department of Cell Biology, Institute for Virus Research, Kyoto University, 53 Shogoin-Kawaracho, Sakyo-ku, Kyoto 606-8507, Japan.
Vet Microbiol. 2011 May 5;149(3-4):307-15. doi: 10.1016/j.vetmic.2010.11.023. Epub 2010 Nov 25.
Based on receptor usage during infection, feline immunodeficiency virus (FIV) isolates can be divided into two groups; those that require feline CD134 (fCD134) as a primary receptor in addition to CXCR4 to enter the cells, and those that require CXCR4 only. Most primary isolates, including strain TM2, belong to the former group and cannot infect a feline astrocyte cell line (G355-5 cells) due to a lack of fCD134 expression. In a previous study, we found that G355-5 cells transduced with fCD134 (termed G355-5/fOX40 cells) were susceptible to strain TM2 and the inoculated cells became persistently infected. In this study, we examined the phenotype of the virus prepared from the persistently infected cells (termed strain TM2PI). Intriguingly, strain TM2PI replicated well in naïve G355-5 cells and the inoculated G355-5 cells (termed G355-5/TM2PI cells) became persistently infected. The infection of TM2PI in G355-5 cells was inhibited by CXCR4 antagonist AMD3100 and TM2PI infected other fCD134-negative, CXCR4-positive cell lines, FeTJ and 3201 cells. Four amino acid substitutions were found in the Env protein of the strain TM2PI when compared with that of the parental strain TM2. Among the substitutions, the Env amino acid position at 407 of TM2PI was substituted to lysine which has been known to be responsible for the FIV tropism for Crandell feline kidney cells. The strain TM2PI will be useful for studying the receptor switching mechanism and FIV pathogenesis in cats.
基于感染过程中受体的使用情况，猫免疫缺陷病毒（FIV）分离株可分为两类；需要猫 CD134（fCD134）作为进入细胞的主要受体，以及仅需要 CXCR4 的。大多数原始分离株，包括 TM2 株，属于前者，由于缺乏 fCD134 的表达，不能感染猫星形胶质细胞系（G355-5 细胞）。在之前的一项研究中，我们发现转导 fCD134 的 G355-5 细胞（称为 G355-5/fOX40 细胞）易感染 TM2 株，接种的细胞持续感染。在这项研究中，我们检查了从持续感染的细胞中制备的病毒的表型（称为 TM2PI 株）。有趣的是，TM2PI 株在原始 G355-5 细胞和接种的 G355-5 细胞（称为 G355-5/TM2PI 细胞）中复制良好，并持续感染。CXCR4 拮抗剂 AMD3100 抑制 TM2PI 在 G355-5 细胞中的感染，TM2PI 感染其他 fCD134 阴性、CXCR4 阳性细胞系 FeTJ 和 3201 细胞。与亲本株 TM2 相比，TM2PI 株的 Env 蛋白发现有四个氨基酸取代。在取代中，TM2PI 的 Env 氨基酸位置 407 被取代为赖氨酸，这已经知道是 FIV 对猫肾细胞的嗜性的原因。TM2PI 株将有助于研究猫中受体转换机制和 FIV 发病机制。
