Co-assembly of Viral Envelope Glycoproteins Regulates Their Polarized Sorting in Neurons

PLoS Pathogens

Gonzalo A. Mardones¹  Juan S. Bonifacino¹  Ginny G. Farías¹  Rafael Mattera¹ 

[1] Cell Biology and Metabolism Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, United States of America

关键词: Neurons;    Neuronal dendrites;    Fluorescence imaging;    Axonal transport;    Axons;    Virus glycoproteins;    Transfection;    Membrane proteins;   

DOI  :  10.1371/journal.ppat.1004107

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Newly synthesized envelope glycoproteins of neuroinvasive viruses can be sorted in a polarized manner to the somatodendritic and/or axonal domains of neurons. Although critical for transneuronal spread of viruses, the molecular determinants and interregulation of this process are largely unknown. We studied the polarized sorting of the attachment (NiV-G) and fusion (NiV-F) glycoproteins of Nipah virus (NiV), a paramyxovirus that causes fatal human encephalitis, in rat hippocampal neurons. When expressed individually, NiV-G exhibited a non-polarized distribution, whereas NiV-F was specifically sorted to the somatodendritic domain. Polarized sorting of NiV-F was dependent on interaction of tyrosine-based signals in its cytosolic tail with the clathrin adaptor complex AP-1. Co-expression of NiV-G with NiV-F abolished somatodendritic sorting of NiV-F due to incorporation of NiV-G•NiV-F complexes into axonal transport carriers. We propose that faster biosynthetic transport of unassembled NiV-F allows for its proteolytic activation in the somatodendritic domain prior to association with NiV-G and axonal delivery of NiV-G•NiV-F complexes. Our study reveals how interactions of viral glycoproteins with the host's transport machinery and between themselves regulate their polarized sorting in neurons.

【 授权许可】

CC BY