Novel Hendra virus variant detected by sentinel surveillance of Australian horses

Annand, Edward J.; Horsburgh, Bethany A.; Xu, Kai; Reid, Peter A.; Poole, Ben; Kantzow, Maximillian C. de; Brown, Nicole; Tweedie, Alison; Michie, Michelle; Grewar, John; Jackson, Anne; Singanallur, Nagendrakumar Balasubramanian; Plain, Karren M.; Tachedjian, Mary; Heide, Brenda van der; Secombe, Cristy; Laing, E.; Sterling, Spencer L; Yan, Lianying; Jackson, Louise A.; Jones, Cheryl; Plowright, Raina K.; Peel, Alison J.; Diallo, Ibrahim S.; Breed, Andrew C.; Broder, Christopher C.; Britton, Philip N; Dhand, Navneet K.; Smith, Ina; Eden, John-Sebastian

doi:10.1101/2021.07.16.452724

Cited by 8 publications

(5 citation statements)

References 49 publications

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“…The detection of cross-reactive HNV antibodies (Abs) in humans and Pteropus bats in Africa underscored that 2 billion people worldwide live in regions threatened by HNV spillovers ( 6 ). Moreover, the recent discovery of a previously unknown HeV genotype ( 7 , 8 ) is an urgent reminder of the HNV zoonotic threat. To date, no approved vaccines or therapeutics for use in people exist against HNV infections ( 9 ).…”

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confidence: 99%

Architecture and antigenicity of the Nipah virus attachment glycoprotein

Wang

Amaya

Addetia

et al. 2022

Science

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Nipah virus (NiV) and Hendra virus (HeV) are zoonotic henipaviruses (HNVs) responsible for outbreaks of encephalitis and respiratory illness. The entry of HNVs into host cells requires the attachment (G) and fusion (F) glycoproteins, which are the main targets of antibody responses. To understand viral infection and host immunity, we determined a cryo–electron microscopy structure of the NiV G homotetrameric ectodomain in complex with the nAH1.3 broadly neutralizing antibody Fab fragment. We show that a cocktail of two nonoverlapping G-specific antibodies neutralizes NiV and HeV synergistically and limits the emergence of escape mutants. Analysis of polyclonal serum antibody responses elicited by vaccination of macaques with NiV G indicates that the receptor binding head domain is immunodominant. These results pave the way for implementing multipronged therapeutic strategies against these deadly pathogens.

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confidence: 99%

Architecture and antigenicity of the Nipah virus attachment glycoprotein

Wang

Amaya

Addetia

et al. 2022

Science

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“…Finally, NiV sequences are ultimately reliant on the PCR primers used to detect the virus in the original sample. If the PCR primers are overly specific, they may systematically miss some viruses (33). Future efforts may want to consider using broader primer sets.…”

Section: Discussionmentioning

confidence: 99%

The genetic diversity of Nipah virus across spatial scales

Azuero,

Lefrancq,

Nikolay

et al. 2023

Preprint

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Nipah virus (NiV), a highly lethal virus in humans, circulates silently inPteropusbats throughout South and Southeast Asia. Difficulty in obtaining genomes from bats means we have a poor understanding of NiV diversity, including how many lineages circulate within a roost and the spread of NiV over increasing spatial scales. Here we develop phylogenetic approaches applied to the most comprehensive collection of genomes to date (N=257, 175 from bats, 73 from humans) from six countries over 22 years (1999-2020). In Bangladesh, where most human infections occur, we find evidence of increased spillover risk from one of the two co-circulating sublineages. We divide the four major NiV sublineages into 15 genetic clusters (emerged 20-44 years ago). Within any bat roost, there are an average of 2.4 co-circulating genetic clusters, rising to 5.5 clusters at areas of 1,500-2,000 km2. Using Approximate Bayesian Computation fit to a spatial signature of viral diversity, we estimate that each genetic cluster occupies an average area of 1.3 million km2(95%CI: 0.6-2.3 million), with 14 clusters in an area of 100,000 km2(95%CI: 6-24). In the few sites in Bangladesh and Cambodia where genomic surveillance has been concentrated, we estimate that most of the genetic clusters have been identified, but only ~15% of overall NiV diversity has been uncovered. Our findings are consistent with entrenched co-circulation of distinct lineages, even within individual roosts, coupled with slow migration over larger spatial scales.

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“…Studies focused on herpesviruses have notably revealed that cell-cell fusion phenotype can significantly differ across isolates of the same viral species [166]. As sequences of henipaviruses detected in domestic and wild species are becoming available [167][168][169], it is important to consider a diversity of henipavirus isolates in comparative studies to understand how cell-cell fusion phenotype varies across viruses and how it correlates with spillover risk.…”

Section: Knowns and Unknowns Of Syncytium Formation And Future Directionsmentioning

confidence: 99%

Drivers and Distribution of Henipavirus-Induced Syncytia: What Do We Know?

Gamble

Yeo

Butler

et al. 2021

Viruses

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Syncytium formation, i.e., cell–cell fusion resulting in the formation of multinucleated cells, is a hallmark of infection by paramyxoviruses and other pathogenic viruses. This natural mechanism has historically been a diagnostic marker for paramyxovirus infection in vivo and is now widely used for the study of virus-induced membrane fusion in vitro. However, the role of syncytium formation in within-host dissemination and pathogenicity of viruses remains poorly understood. The diversity of henipaviruses and their wide host range and tissue tropism make them particularly appropriate models with which to characterize the drivers of syncytium formation and the implications for virus fitness and pathogenicity. Based on the henipavirus literature, we summarized current knowledge on the mechanisms driving syncytium formation, mostly acquired from in vitro studies, and on the in vivo distribution of syncytia. While these data suggest that syncytium formation widely occurs across henipaviruses, hosts, and tissues, we identified important data gaps that undermined our understanding of the role of syncytium formation in virus pathogenesis. Based on these observations, we propose solutions of varying complexity to fill these data gaps, from better practices in data archiving and publication for in vivo studies, to experimental approaches in vitro.

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Novel Hendra virus variant detected by sentinel surveillance of Australian horses

Cited by 8 publications

References 49 publications

Architecture and antigenicity of the Nipah virus attachment glycoprotein

Architecture and antigenicity of the Nipah virus attachment glycoprotein

The genetic diversity of Nipah virus across spatial scales

Drivers and Distribution of Henipavirus-Induced Syncytia: What Do We Know?

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