Nipah virus entry can occur by macropinocytosis

• Published in: Virology (New York, N.Y.) Vol. 395; no. 2; pp. 298 - 311
• Main Authors: Pernet, Olivier, Pohl, Christine, Ainouze, Michelle, Kweder, Hasan, Buckland, Robin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.12.2009
• Subjects: 60 APPLIED LIFE SCIENCES; AMINO ACIDS; Animals; Antivirals; CARBOXYLIC ACIDS; CHO Cells; Cricetinae; Cricetulus; Entry; Hendra virus; Hepatitis E virus; Hydrogen-Ion Concentration; HYDROXY ACIDS; Infectious Disease; Macropinocytosis; MEMBRANE PROTEINS; MICROORGANISMS; MUTATIONS; Nipah virus; Nipah Virus - physiology; ORGANIC ACIDS; ORGANIC COMPOUNDS; Paramyxoviridae; Paramyxovirus; PARASITES; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; PROTEINS; RECEPTORS; Recombinant Proteins; RESIDUES; TYROSINE; Viral Proteins - genetics; Viral Proteins - metabolism; Virus Internalization - drug effects; VIRUSES; Entry; Nipah virus; Antivirals; Macropinocytosis
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2009.09.016

Abstract 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.