Project description:Nipah virus is a deadly paramyxovirus with 40-75% mortality and >750 cases since 1998. Currently there are no clinically approved vaccines or therapeutics to target infection. Nipah is an enveloped virus with two surface glycoproteins, the trimeric fusion (F) and tetrameric attachment glycoprotein (G). G is responsible for cellular attachment via binding to ephrin B2/B3. Glycosylation of Nipah G and its effects on receptor engagement has not previously been studied but is important as glycosylation impacts immunogenicity, receptor binding and structural conformations for other enveloped virus glycoproteins. Our phylogenetic and mass spectrometry analysis of sitespecific N-glycans of the Nipah G Malaysia strain revealed how N-glycosylation has evolved since the appearance of the virus in 1998. We discovered that the N481 N-glycosite is not conserved and although the glycan does not directly contribute to receptor binding, the threonine/serine in the glycosylation sequon is critical for maintaining long-range stability of individual G subunits that facilitates ephrin B2 binding affinity. Together, these data reveal plasticity of N-glycosylation sites across Nipah species and the presence of hydrogen bonding networks that contribute to G stability and host engagement, which is valuable information for understanding virus attachment/entry mechanisms as well as the rationale design of structure-based vaccines.
Project description:Nipah virus (NiV) is a highly pathogenic, negative strand RNA paramyxovirus that has recently emerged from flying foxes to cause serious human disease. To study the poorly-understood role of nonstructural NiV proteins in NiV pathogenesis, we generated recombinant viruse lacking the expression of accesory NiV C protein (NiV∆C).
Project description:Nipah virus (NiV) is an emerging paramyxovirus which causes severe respiratory illness and deathly encephalitis in humans.Improving the ability of vaccines to induce strong, cellular, and humoral immune responses, remains the challenge to respond to Nipah and future Henipavirus infections rapidly and efficiently. A CD40.NiV vaccine has been engineered by fusing to the anti-CD40 monoclonal Ab the ectodomain of the Nipah G protein (Bangladesh strain) and immunogenic and conserved NiV F and N peptides. In mice, CD40.NiV promotes poly-antigenic T cell responses and significantly improves anti-NiV G IgG responses compared to the non-targeted NiV G immunogenic protein, in terms of avidity and neutralization potency. Immunogenicity was confirmed in the AGM (African Green Monkey) model, with induction of cross-neutralizing sera against circulating NiV strains and Hendra virus (HeV). Challenge experiment using NiV-B strain demonstrated the high protective efficacy of the vaccine with 100% survival in vaccinated group as compared to 100% lethality in controls. Surviving animals did not exhibit NiV viral replication in the blood, organs and swabs suggesting a sterilizing immunity conferred by the CD40.NiV vaccine. Taken together, results obtained with CD40.NiV vaccine are highly promising in terms of breadth and viral efficacy against NiV.
2024-02-02 | GSE245374 | GEO
Project description:Infection of Marmosets with Nipah virus Bangladesh
Project description:A novel henipavirus (HNV) named Langya virus (LayV) was isolated in human patients in China in August 2022. It is closely related to Mòjiāng virus (MojV) and represents the first instance of HNV zoonosis to humans outside of Nipah virus (NiV) and Hendra viruses (HeV). Within this work, mass spectrometry glycoproteomic analysis revealed that although the LayV F protein has reduced glycosylation compared to its NiV and HeV counterparts, a unique glycan was identified positioned at the DIII apex, shielding a previously identified site of vulnerability in NiV F.
Project description:Nipah virus (NiV) is a recently emerged zoonotic Paramyxovirus that causes regular outbreaks in East Asia with mortality rate exceeding 75%. Major cellular targets of NiV infection are endothelial cells and neurons. To better understand virus-host interaction, we analysed the transcriptome profile of NiV infection in primary human umbilical vein endothelial cells. We found that NiV infection strongly induces genes involved in interferon response in endothelial cells. Among the top ten upregulated genes, we identified the chemokine CXCL10 (interferon-induced protein 10, IP-10), an important chemoattractant involved in the generation of inflammatory immune response and neurotoxicity. We performed microarray gene expression profiling of NiV infected HUVEC cell (2 replicates) and of uninfected HUVEC cell (2 replicates).
Project description:Nipah virus (NiV) is a recently emerged zoonotic Paramyxovirus that causes regular outbreaks in East Asia with mortality rate exceeding 75%. Major cellular targets of NiV infection are endothelial cells and neurons. To better understand virus-host interaction, we analysed the transcriptome profile of NiV infection in primary human umbilical vein endothelial cells. We found that NiV infection strongly induces genes involved in interferon response in endothelial cells. Among the top ten upregulated genes, we identified the chemokine CXCL10 (interferon-induced protein 10, IP-10), an important chemoattractant involved in the generation of inflammatory immune response and neurotoxicity.