Envelope–Receptor Interactions in Nipah Virus Pathobiology

Abstract

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.

Interactions of Human Complement with Virus Particles Containing the Nipah Virus Glycoproteins

“…The high mortality rate of NiV infections and the potential use of the virus as an agent of bioterrorism have raised intense interest in developing vaccines or therapeutic approaches targeting the NiV glycoproteins (7,8,19,29). In view of the potent role that complement can play in paramyxovirus neutralization (16,17,21,36), the goal of the work described here was to determine the role of complement in the neutralization of particles containing the NiV glycoproteins.…”

“…Nipah virus is a biosafety level 4 (BSL4) emerging viral pathogen. NiV has been designated a priority pathogen for study due to the high mortality rates following human infections (ϳ45 to 70%), the potential impact on farm economies, and the potential for use as a bioterrorism agent (11,19,20). There are currently no approved vaccines or therapeutics for NiV (7).…”

Nodavirus Infection of Sea Bass (Dicentrarchus labrax) Induces Up-Regulation of Galectin-1 Expression with Potential Anti-Inflammatory Activity

“…In addition to their multiple immunoregulatory activities, galectins may bind to the envelope glycoproteins and inhibit viral fusion to the host cell membrane, thereby exerting direct antiviral effects. Galectin-1 exhibits antiviral properties against Nipah virus, possibly by interaction with specific N-glycans on the viral envelope (50,52). Although our results suggest that Sbgalectin-1 could have similar activity, and explain the observed differential Mx protein expression, the direct binding and/or neutralization of nodavirus by Sbgalectin-1 remains to be demonstrated.…”

Transcriptome Signature of Nipah Virus Infected Endothelial Cells

“…Some of patients develop in addition respiratory symptoms. Death occurs in 40 to 90% within an average time of 10 days post fever, due to the severity of the cerebral damages (Lee, 2007). The pathology is characterized by a systemic vasculitis with syncytia formation of microvascular endothelial and epithelial cells (Fig.…”