N-Glycans on the Rift Valley Fever Virus Envelope Glycoproteins Gn and Gc Redundantly Support Viral Infection via DC-SIGN.
N-Glycans on the Rift Valley Fever Virus Envelope Glycoproteins Gn and Gc Redundantly Support Viral Infection via DC-SIGN.
复制标题
DOI：
10.3390/v8050149
复制
发表时间：
2016-05-23
期刊：
影响因子：
--
通讯作者：
Ikegami T
中科院分区：
文献类型：
--
作者：
Phoenix I;Nishiyama S;Lokugamage N;Hill TE;Huante MB;Slack OA;Carpio VH;Freiberg AN;Ikegami T
裂谷热是一种由蚊子传播的人畜共患疾病，感染人类和反刍动物。树突状细胞特异性细胞间黏附分子3(ICAM-3)结合非整合素(DC-SIGN)是细小病毒属成员的受体。裂谷热病毒糖蛋白(Gn/GC)编码5个N-糖链序列(天冬酰胺(N)-任何氨基酸(X)-丝氨酸(S)/苏氨酸(T))，分别位于N438(Gn)和N794、N829、N1035和N1077(GC)位置。通过DC-SIGN感染病毒的N-糖基化特征和意义尚未阐明。首先利用GC天冬酰胺(N)到谷氨酰胺(Q)突变体对GC N-糖基化进行了评价。随后，我们构建了一系列编码N-to-Q突变的重组RVFV MP-12株突变体，并对每个突变体在稳定表达DC-SIGN的Jurkat细胞中的感染性进行了评价。结果表明，GC N794、N1035和N1077是N-糖基化的，而N829不是。GC N1077是一种非均相N-糖基化产物。RVFV GC有两种不同的N-糖型：“GC-大”和“GC-小”，N1077负责“GC-大”带。与不表达DC-SIGN的细胞相比，表达DC-SIGN的细胞感染RVFV的细胞增多。在Gn N438或GC N1077存在时，通过DC-SIGN的感染增加。我们的研究表明，GC和Gn表面糖蛋白上的N-糖链通过DC-SIGN冗余地支持RVFV的感染。
Rift Valley fever is a mosquito-transmitted, zoonotic disease that infects humans and ruminants. Dendritic cell specific intercellular adhesion molecule 3 (ICAM-3) grabbing non-integrin (DC-SIGN) acts as a receptor for members of the phlebovirus genus. The Rift Valley fever virus (RVFV) glycoproteins (Gn/Gc) encode five putative N-glycan sequons (asparagine (N)–any amino acid (X)–serine (S)/threonine (T)) at positions: N438 (Gn), and N794, N829, N1035, and N1077 (Gc). The N-glycosylation profile and significance in viral infection via DC-SIGN have not been elucidated. Gc N-glycosylation was first evaluated by using Gc asparagine (N) to glutamine (Q) mutants. Subsequently, we generated a series of recombinant RVFV MP-12 strain mutants, which encode N-to-Q mutations, and the infectivity of each mutant in Jurkat cells stably expressing DC-SIGN was evaluated. Results showed that Gc N794, N1035, and N1077 were N-glycosylated but N829 was not. Gc N1077 was heterogeneously N-glycosylated. RVFV Gc made two distinct N-glycoforms: “Gc-large” and “Gc-small”, and N1077 was responsible for “Gc-large” band. RVFV showed increased infection of cells expressing DC-SIGN compared to cells lacking DC-SIGN. Infection via DC-SIGN was increased in the presence of either Gn N438 or Gc N1077. Our study showed that N-glycans on the Gc and Gn surface glycoproteins redundantly support RVFV infection via DC-SIGN.