Section on Directed Gene Transfer, Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
Retrovirology. 2012 Jun 12;9:51. doi: 10.1186/1742-4690-9-51.
Both cell-free and cell-associated infection routes are important for retroviral dissemination. Regardless of the mechanism, the driving force of retroviral entry is the interaction between the viral envelope and its receptor. To date it remains unclear how decreased affinity of viruses for their receptors affects viral cell-free infection, cell-cell transmission, and spreading kinetics. We have previously characterized a mutant form of the amphotropic murine retrovirus receptor human phosphate transporter 2 (PiT2) wherein the single substitution of a glutamic acid for the lysine residue at position 522 of this receptor is sufficient to render it to function as a gibbon ape leukemia virus (GALV) receptor.
In this study we analyzed the binding affinity of the mutant receptor PiT2K522E and determined that it has a 1000 fold decreased GALV envelope binding affinity compared to the GALV wild type receptor. The decreased affinity does not restrict the initiation of cell-free GALV infection. The diminished binding affinity does, however, correlate with a decrease in the ability of GALV to spread in cells expressing this mutant receptor.
The reduced ability of GALV to subsequently spread among cells expressing PiT2K522E is likely resulted from reduced cell-cell transmission, the decreased ability of PiT2K522E-expressing cells to establish superinfection interference, and attendant cytopathic affects.
游离细胞和细胞相关感染途径对于逆转录病毒的传播都很重要。无论机制如何，逆转录病毒进入的驱动力是病毒包膜与其受体之间的相互作用。迄今为止，病毒对其受体亲和力的降低如何影响病毒游离感染、细胞间传播和扩散动力学尚不清楚。我们之前已经对嗜性鼠逆转录病毒受体人磷酸转运蛋白 2（PiT2）的一种突变形式进行了表征，其中该受体中第 522 位赖氨酸残基被谷氨酸取代，足以使其作为长臂猿白血病病毒（GALV）受体发挥作用。
在这项研究中，我们分析了突变受体 PiT2K522E 的结合亲和力，并确定其与 GALV 野生型受体相比，GALV 包膜结合亲和力降低了 1000 倍。亲和力的降低并不限制游离 GALV 感染的起始。然而，这种降低的亲和力与在表达这种突变受体的细胞中 GALV 传播能力的下降相关。
表达 PiT2K522E 的细胞中 GALV 随后传播能力的降低可能是由于细胞间传播减少、表达 PiT2K522E 的细胞建立超感染干扰的能力降低以及伴随的细胞病变效应所致。
