Cell entry by a novel European filovirus requires host endosomal cysteine proteases and Niemann-Pick C1.

Abstract:

:Lloviu virus (LLOV), a phylogenetically divergent filovirus, is the proposed etiologic agent of die-offs of Schreibers's long-fingered bats (Miniopterus schreibersii) in western Europe. Studies of LLOV remain limited because the infectious agent has not yet been isolated. Here, we generated a recombinant vesicular stomatitis virus expressing the LLOV spike glycoprotein (GP) and used it to show that LLOV GP resembles other filovirus GP proteins in structure and function. LLOV GP must be cleaved by endosomal cysteine proteases during entry, but is much more protease-sensitive than EBOV GP. The EBOV/MARV receptor, Niemann-Pick C1 (NPC1), is also required for LLOV entry, and its second luminal domain is recognized with high affinity by a cleaved form of LLOV GP, suggesting that receptor binding would not impose a barrier to LLOV infection of humans and non-human primates. The use of NPC1 as an intracellular entry receptor may be a universal property of filoviruses.

journal_name

Virology

journal_title

Virology

authors

Ng M,Ndungo E,Jangra RK,Cai Y,Postnikova E,Radoshitzky SR,Dye JM,Ramírez de Arellano E,Negredo A,Palacios G,Kuhn JH,Chandran K

doi

10.1016/j.virol.2014.08.019

subject

Has Abstract

pub_date

2014-11-01 00:00:00

pages

637-646

eissn

0042-6822

issn

1096-0341

pii

S0042-6822(14)00399-7

journal_volume

468-470

pub_type

杂志文章

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