Functional Analysis of the Fusion and Attachment Glycoproteins of Mojiang Henipavirus

Abstract

Mojiang virus (MojV) is the first henipavirus identified in a rodent and known only by sequence data, whereas all other henipaviruses have been isolated from bats (Hendra virus, Nipah virus, Cedar virus) or discovered by sequence data from material of bat origin (Ghana virus). Ephrin-B2 and -B3 are entry receptors for Hendra and Nipah viruses, but Cedar virus can utilize human ephrin-B1, -B2, -A2 and -A5 and mouse ephrin-A1. However, the entry receptor for MojV remains unknown, and its species tropism is not well characterized. Here, we utilized recombinant full-length and soluble forms of the MojV fusion (F) and attachment (G) glycoproteins in membrane fusion and receptor tropism studies. MojV F and G were functionally competent and mediated cell–cell fusion in primate and rattine cells, albeit with low levels and slow fusion kinetics. Although a relative instability of the pre-fusion conformation of a soluble form of MojV F was observed, MojV F displayed significantly greater fusion activity when heterotypically paired with Ghana virus G. An exhaustive investigation of A- and B-class ephrins indicated that none serve as a primary receptor for MojV. The MojV cell fusion phenotype is therefore likely the result of receptor restriction rather than functional defects in recombinant MojV F and G glycoproteins.

The characterization of multiple novel paramyxoviruses highlights the diverse nature of the subfamilyOrthoparamyxovirinae

“…A possible argument against this hypothesis might be that Mòjiāng virus, the first rodent-borne henipavirus to be discovered, has been shown to be incapable of using the same host-entry pathways as other henipaviruses due to differences in its RBP ( Rissanen et al. 2017 ; Cheliout Da Silva et al. 2021 ).…”

The characterization of multiple novel paramyxovirus species highlights the diverse nature of the subfamily Orthoparamyxovirinae

“…A question that remains to be resolved is whether the members of these separate clades are equally pathogenic as their sister clade counterparts and, especially in the case of the henipaviruses, if they have the same zoonotic potential. A possible argument against this hypothesis might be that Mòjiāng virus, the first rodent-borne henipavirus to be discovered, has been shown to be incapable of using the same host-entry pathways as other henipaviruses due to antigenic differences in its G protein [49, 50]. Interestingly, the availability of additional sequences of related viruses has made it apparent that members of this rodent-/shrew-borne henipavirus clade contain a conserved ORF coding for a transmembrane protein nested within the F gene.…”

Discovery and Genomic Characterization of a Novel Henipavirus, Angavokely virus, from fruit bats in Madagascar

“…Cross-species viral spillover necessitates effective inter-species transmission, which first requires a virus to successfully enter the cells of diverse host species. In general, HNVs use the highly-conserved ephrin family of proteins, both type A and type B, as cell entry receptors (1, 8, 14–16). A notable exception to this pattern is MojV, which does not use ephrin proteins—or the sialic acid and CD150 receptors common to non-HNV paramyxoviruses—to gain cell entry (14, 17).…”

“…In general, HNVs use the highly-conserved ephrin family of proteins, both type A and type B, as cell entry receptors (1, 8, 14–16). A notable exception to this pattern is MojV, which does not use ephrin proteins—or the sialic acid and CD150 receptors common to non-HNV paramyxoviruses—to gain cell entry (14, 17). Indeed, as of yet, the viral entry receptor for MojV—and the closely related GAKV and DARV—remain unknown.…”