Filovirus receptor NPC1 contributes to species-specific patterns of ebolavirus susceptibility in bats
Filovirus receptor NPC1 contributes to species-specific patterns of ebolavirus susceptibility in bats
复制标题
DOI：
10.7554/elife.11785
复制
发表时间：
2015-12-23
期刊：
影响因子：
7.7
通讯作者：
Chandran, Kartik
中科院分区：
文献类型：
--
作者：
Ng, Melinda;Ndungo, Esther;Chandran, Kartik
影响埃博拉病毒（EBOV）和其他丝状病毒宿主范围和外溢的生物学因素仍然是个谜。虽然丝状病毒感染多种哺乳动物细胞系，但我们报告了非洲稻草色果蝠（Eidolon helvum）的细胞对EBOV感染具有抗性。这可能是由于线状病毒受体NPC1的一个氨基酸改变，大大降低了EBOV-NPC1相互作用的亲和力。我们在蝙蝠NPC1中发现阳性选择信号集中在病毒受体界面，在控制EBOV感染的Eidolon helvum细胞的相同残基上信号最强。我们的工作确定NPC1是蝙蝠线状病毒易感性的遗传决定因素，并表明一些NPC1变异反映了宿主对减少线状病毒复制和毒力的适应。单个病毒突变可以逃避受体控制，揭示了一种代偿性病毒进化途径和自然界中线状病毒宿主范围扩大的潜在途径。
Biological factors that influence the host range and spillover of Ebola virus (EBOV) and other filoviruses remain enigmatic. While filoviruses infect diverse mammalian cell lines, we report that cells from African straw-colored fruit bats (Eidolon helvum) are refractory to EBOV infection. This could be explained by a single amino acid change in the filovirus receptor, NPC1, which greatly reduces the affinity of EBOV-NPC1 interaction. We found signatures of positive selection in bat NPC1 concentrated at the virus-receptor interface, with the strongest signal at the same residue that controls EBOV infection in Eidolon helvum cells. Our work identifies NPC1 as a genetic determinant of filovirus susceptibility in bats, and suggests that some NPC1 variations reflect host adaptations to reduce filovirus replication and virulence. A single viral mutation afforded escape from receptor control, revealing a pathway for compensatory viral evolution and a potential avenue for expansion of filovirus host range in nature.