The intracellular cargo receptor ERGIC-53 is required for the production of infectious arenavirus, coronavirus, and filovirus particles.
Arenaviruses and hantaviruses cause severe human disease. Little is known regarding host proteins required for their propagation. We identified human proteins that interact with the glycoproteins (GPs) of a prototypic arenavirus and hantavirus and show that the lectin endoplasmic reticulum (ER)-Golgi intermediate compartment 53 kDa protein (ERGIC-53), a cargo receptor required for glycoprotein trafficking within the early exocytic pathway, associates with arenavirus, hantavirus, coronavirus, orthomyxovirus, and filovirus GPs. ERGIC-53 binds to arenavirus GPs through a lectin-independent mechanism, traffics to arenavirus budding sites, and is incorporated into virions. ERGIC-53 is required for arenavirus, coronavirus, and filovirus propagation; in its absence, GP-containing virus particles form but are noninfectious, due in part to their inability to attach to host cells. Thus, we have identified a class of pathogen-derived ERGIC-53 ligands, a lectin-independent basis for their association with ERGIC-53, and a role for ERGIC-53 in the propagation of several highly pathogenic RNA virus families.
Department of Medicine, Division of Immunobiology, University of Vermont, Burlington, VT 05405, USA; Cellular, Molecular and Biomedical Sciences Graduate Program, University of Vermont, Burlington, VT 05405, USA.
Joseph P
JP
Klaus
Philip
P
Eisenhauer
Joanne
J
Russo
Anne B
AB
Mason
Danh
D
Do
Benjamin
B
King
Douglas
D
Taatjes
Cromwell
C
Cornillez-Ty
Jonathan E
JE
Boyson
Markus
M
Thali
Chunlei
C
Zheng
Lujian
L
Liao
John R
JR
Yates
Bin
B
Zhang
Bryan A
BA
Ballif
Jason W
JW
Botten
D018050:Arenavirus / Q000502:physiology*; D002460:Cell Line; D017934:Coronavirus / Q000502:physiology*; D016563:Filoviridae / Q000502:physiology*; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D037241:Mannose-Binding Lectins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D021381:Protein Transport; D014764:Viral Proteins / Q000378:metabolism; D019065:Virus Assembly
D006023:Glycoproteins; C084004:LMAN1 protein, human; D037241:Mannose-Binding Lectins; D008565:Membrane Proteins; D014764:Viral Proteins