Studies on the mechanisms of the host range determination of lentiviruses from carnivora

人类免疫缺陷病毒（HIV）属于慢病毒属，可引起人类免疫缺陷。动物也有自己的慢病毒，并引起各种疾病。猫也有一种叫做猫免疫缺陷病毒（FIV）的致病性慢病毒，FIV在大鼠中引起的免疫缺陷类似于人类的HIV感染。大型猫科动物如狮子也有慢病毒，但这些病毒在自然宿主中是无致病性的。阐明猫科慢病毒宿主范围的确定机制，对于应对猫科慢病毒新型感染的出现具有重要意义。我们分析了FIV感染猫神经胶质细胞系G355-5细胞的机制。FIV菌株Petaluma（亚型A）感染G355-5细胞，而不考虑猫CD134 （fCD134）的表达，猫CD134是t淋巴性FIV的主要受体。另一方面，菌株TM2 （B亚型）需要异位表达fCD134才能感染G355-5细胞。有趣的是，offCD134的强表达抑制了菌株Petaluma在G355-5细胞中的感染。此外，fCD134的表达抑制了菌株TM2从感染的G855-5细胞中高效释放病毒。经fCD134转导的菌株tm2感染G355-5细胞（G355-5/fOX40细胞）后进入持续感染状态。在感染后50天，感染细胞将感染性FIV颗粒释放到培养基中，将该病毒命名为菌株TM2PI。在缺乏fCD134的情况下，TM2PI感染G355-5细胞，表明菌株TM2在G355-5细胞中突变为不依赖fCD134的菌株。此外，细胞也进入持续感染状态，无需与未感染的G355-5细胞共培养即可维持。由于病毒和产生细胞都没有经过基因工程技术的修饰，因此产生细胞可能适合于制备用于疫苗的病毒抗原。

Human immunodeficiency virus (HIV) belongs to the genus lentivirus and induces immunodeficiency in humans. Animals also have own lentiviruses and cause a variety of diseases. Cats also have a pathogenic lentivirus called feline immunodeficiency virus (FIV) and FIV induces immunodeficiency in rats similar to the HIV infection in humans. Large felids such as lions also have lentiviruses, however the viruses are non-pathogenic in natural hosts. To elucidate the mechanisms on the determination of the host range of the feline lentiviruses is important to cope with the emergence of the novel lentiviral infections in felids. We analyzed the mechanisms of FIV infection in a feline glial cell line termed G355-5 cells. FIV strain Petaluma (subtype A) infected the G355-5 cells irrespective of the expression of feline CD134 (fCD134), primary receptor for T-lymphotropic FIV. On the other hand, strain TM2 (subtype B) required the ectopic expression of fCD134 to infect the G355-5 cells. Intriguingly, the strong expression of offCD134 suppressed the infection by strain Petaluma in the G355-5 cells. In addition, the expression of fCD134 suppressed the efficient viral release of strain TM2 from the infected G855-5 cells. The strain TM2-infected G355-5 cells transduced with fCD134 (G355-5/fOX40 cells) became a state of persistent infection. At 50 days post-infection, the infected cells released the infectious FIV particles into the culture medium and the virus was designated as strain TM2PI. TM2PI infected naive G355-5 cells in the absence of fCD134, indicating that strain TM2 mutated in the G355-5 cells to be an fCD134-independent strain. Furthermore, the cells also became a state of persistent infection and can be maintained without coculturing with uninfected G355-5 cells. Because both virus and producer cells were not modified by the genetic engineering techniques, the producer cells may be suitable for antigen preparation of the virus for vaccines.