Envelope-receptor interactions in Nipah virus pathobiology.
Nipah (NiV) and Hendra (HeV) viruses are members of the newly defined Henipavirus genus of the Paramyxoviridae. Nipah virus (NiV) is an emergent paramyxovirus that causes fatal encephalitis in up to 70% of infected patients, and there is increasing evidence of human-to-human transmission. NiV is designated a priority pathogen in the NIAID Biodefense Research Agenda, and could be a devastating agent of agrobioterrorism if used against the pig farming industry. Endothelial syncytium is a pathognomonic feature of NiV infections, and is mediated by the fusion (F) and attachment (G) envelope glycoproteins. This review summarizes what is known about the pathophysiology of NiV infections, and documents the identification of the NiV receptor. EphrinB2, the NiV and HeV receptor, is expressed on endothelial cells and neurons, consistent with the known cellular tropism for NiV. We discuss how the identification of the henipahvirus receptor sheds light on the pathobiology of NiV infection, and how it will spur the rational development of effective therapeutics. In addition, ephrinB3, a related protein, can serve as an alternative receptor, and we suggest that differential usage of ephrinB2 versus B3 may explain the variant pathogenic profiles observed between NiV and HeV. Thus, identifying the NiV receptors opens the door for a more comprehensive analysis of the envelope-receptor interactions in NiV pathobiology. Finally, we also describe how galectin-1 (an innate immune defense lectin) can interact with specific N-glycans on the Nipah envelope fusion protein, underscoring the potential role that innate immune defense mechanisms may play against emerging pathogens.
Lee
Benhur
B
UCLA/MIMG, 3825 Mol Sci Bldg, East Los Angeles, CA 90095-1489, USA. bleebhl@ucla.edu
D000818:Animals; D023482:Bioterrorism; D021821:Communicable Diseases, Emerging / Q000453:epidemiology / Q000821:virology; D004196:Disease Outbreaks; D036388:Ephrin-B2 / Q000502:physiology*; D036389:Ephrin-B3 / Q000502:physiology*; D037483:Galectin 1 / Q000276:immunology; D045464:Henipavirus Infections / Q000453:epidemiology / Q000503:physiopathology / Q000821:virology*; D006801:Humans; D045405:Nipah Virus / Q000472:pathogenicity* / Q000502:physiology; D011991:Receptors, Virus / Q000502:physiology*; D014759:Viral Envelope Proteins / Q000502:physiology*
D036388:Ephrin-B2; D036389:Ephrin-B3; D037483:Galectin 1; D011991:Receptors, Virus; D014759:Viral Envelope Proteins