Nipah virus entry can occur by macropinocytosis.
Nipah virus (NiV) is a zoonotic biosafety level 4 paramyxovirus that emerged recently in Asia with high mortality in man. NiV is a member, with Hendra virus (HeV), of the Henipavirus genus in the Paramyxoviridae family. Although NiV entry, like that of other paramyxoviruses, is believed to occur via pH-independent fusion with the host cell's plasma membrane we present evidence that entry can occur by an endocytic pathway. The NiV receptor ephrinB2 has receptor kinase activity and we find that ephrinB2's cytoplasmic domain is required for entry but is dispensable for post-entry viral spread. The mutation of a single tyrosine residue (Y304F) in ephrinB2's cytoplasmic tail abrogates NiV entry. Moreover, our results show that NiV entry is inhibited by constructions and drugs specific for the endocytic pathway of macropinocytosis. Our findings could potentially permit the rapid development of novel low-cost antiviral treatments not only for NiV but also HeV.
Molecular Basis of Paramyxovirus Entry, INSERM U758 Virologie Humaine IFR 128 BioSciences Gerland-Lyon Sud, 21 Avenue Tony Garnier, 69365 Lyon Cedex 07, France.
Olivier
O
Pernet
Christine
C
Pohl
Michelle
M
Ainouze
Hasan
H
Kweder
Robin
R
Buckland
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006863:Hydrogen-Ion Concentration; D045405:Nipah Virus / Q000502:physiology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011994:Recombinant Proteins; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D053586:Virus Internalization / Q000187:drug effects*
D000081082:Phosphoinositide-3 Kinase Inhibitors; D011994:Recombinant Proteins; D014764:Viral Proteins