Transmission Routes for Nipah Virus from Malaysia and Bangladesh

Clayton, Bronwyn A.; Middleton, Deborah; Bergfeld, Jemma; Haining, Jessica; Arkinstall, Rachel; Wang, Lin‐Fa; Marsh, Glenn A.

doi:10.3201/eid1812.120875

Cited by 99 publications

(99 citation statements)

References 26 publications

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“…African green monkey model indicated that NiV-BD is more pathogenic with narrower window for passive antibody therapy than NiV-MY (15) . Similar study using ferret model shown increased oral shedding with more rapid onset and higher levels of viral replication in the respiratory tract of NiV-BD than NiV-MY (16,17) . These properties of NiV-BD explained the shorter incubation, more respiratory symptoms, human to human transmission and higher case fatality in cases from Bangladesh and India.…”

Section: The Virussupporting

confidence: 53%

Nipah Virus: A Hidden and Continuous Threat to Humankind

Abhishek¹

2018

jmscr

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Section: The Virussupporting

confidence: 53%

Nipah Virus: A Hidden and Continuous Threat to Humankind

Abhishek¹

2018

jmscr

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“…For example, we have designed other reporter-expressing viruses with their own unique advantages for in vivo studies, such as an NiV with a secreted Gaussia luciferase-P2A-EGFP dual-expression cassette that can be used to monitor viral load directly in tissues by bioluminescence imaging or indirectly by measuring Gaussia luciferase activity in serum (11). Future in vivo studies with these reporter constructs and recombinant henipavirus chimeras will not only reveal insights into NiV and HeV pathogenesis but also open the door to similar investigations into different NiV strains (e.g., the Malaysian strain versus the more diverse Bangladeshi strains, which also appear to differ significantly in both epidemiological and experimental contexts [50][51][52]) and newly discovered henipaviruses (such as Cedar virus and the African bat henipavirus Gh-M74a [4,5]). …”

Section: Discussionmentioning

confidence: 99%

Efficient Reverse Genetics Reveals Genetic Determinants of Budding and Fusogenic Differences between Nipah and Hendra Viruses and Enables Real-Time Monitoring of Viral Spread in Small Animal Models of Henipavirus Infection

Yun

Park

Hill

et al. 2015

J Virol

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Nipah virus (NiV) and Hendra virus (HeV) are closely related henipaviruses of the Paramyxovirinae. Spillover from their fruit bat reservoirs can cause severe disease in humans and livestock. Despite their high sequence similarity, NiV and HeV exhibit apparent differences in receptor and tissue tropism, envelope-mediated fusogenicity, replicative fitness, and other pathophysiologic manifestations. To investigate the molecular basis for these differences, we first established a highly efficient reverse genetics system that increased rescue titers by >3 log units, which offset the difficulty of generating multiple recombinants under constraining biosafety level 4 (BSL-4) conditions. We then replaced, singly and in combination, the matrix (M), fusion (F), and attachment glycoprotein (G) genes in mCherry-expressing recombinant NiV (rNiV) with their HeV counterparts. These chimeric but isogenic rNiVs replicated well in primary human endothelial and neuronal cells, indicating efficient heterotypic complementation. The determinants of budding efficiency, fusogenicity, and replicative fitness were dissociable: HeV-M budded more efficiently than NiV-M, accounting for the higher replicative titers of HeV-M-bearing chimeras at early times, while the enhanced fusogenicity of NiV-G-bearing chimeras did not correlate with increased replicative fitness. Furthermore, to facilitate spatiotemporal studies on henipavirus pathogenesis, we generated a firefly luciferase-expressing NiV and monitored virus replication and spread in infected interferon alpha/beta receptor knockout mice via bioluminescence imaging. While intraperitoneal inoculation resulted in neuroinvasion following systemic spread and replication in the respiratory tract, intranasal inoculation resulted in confined spread to regions corresponding to olfactory bulbs and salivary glands before subsequent neuroinvasion. This optimized henipavirus reverse genetics system will facilitate future investigations into the growing numbers of novel henipaviruslike viruses. IMPORTANCENipah virus (NiV) and Hendra virus (HeV) are recently emergent zoonotic and highly lethal pathogens with pandemic potential. Although differences have been observed between NiV and HeV replication and pathogenesis, the molecular basis for these differences has not been examined. In this study, we established a highly efficient system to reverse engineer changes into replication-competent NiV and HeV, which facilitated the generation of reporter-expressing viruses and recombinant NiV-HeV chimeras with substitutions in the genes responsible for viral exit (the M gene, critical for assembly and budding) and viral entry (the G [attachment] and F [fusion] genes). These chimeras revealed differences in the budding and fusogenic properties of the M and G proteins, respectively, which help explain previously observed differences between NiV and HeV. Finally, to facilitate future in vivo studies, we monitored the replication and spread of a bioluminescent reporter-expressing NiV in susceptible mice; th...

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“…Cats infected with NiV in the laboratory develop a severe respiratory and systemic disease 6 to 13 days after infection [80]. In addition, ferrets were shown to be a suitable model for Henipavirus infection, developing both respiratory and neurological disease [26,79,81]. Several murine models have been established recently, presenting an advantage of the availability of many experimental tools for further studies.…”

Section: Animal Modelsmentioning

confidence: 99%

Henipavirus pathogenesis and antiviral approaches

Mathieu

Horvat

2015

Expert Review of Anti-infective Therapy

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Hendra virus and Nipah virus are closely related, recently emerged zoonotic paramyxoviruses, belonging to the Henipavirus genus. Both viruses induce generalized vasculitis affecting particularly the respiratory tract and CNS. The exceptionally broad species tropism of Henipavirus, the high case fatality rate and person-to-person transmission associated with Nipah virus outbreaks emphasize the necessity of effective antiviral strategies for these intriguing threatening pathogens. Current therapeutic approaches, validated in animal models, target early steps in viral infection; they include the use of neutralizing virus-specific antibodies and blocking membrane fusion with peptides that bind the viral fusion protein. A better understanding of Henipavirus pathogenesis is critical for the further advancement of antiviral treatment, and we summarize here the recent progress in the field.

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Transmission Routes for Nipah Virus from Malaysia and Bangladesh

Cited by 99 publications

References 26 publications

Nipah Virus: A Hidden and Continuous Threat to Humankind

Nipah Virus: A Hidden and Continuous Threat to Humankind

Efficient Reverse Genetics Reveals Genetic Determinants of Budding and Fusogenic Differences between Nipah and Hendra Viruses and Enables Real-Time Monitoring of Viral Spread in Small Animal Models of Henipavirus Infection

Henipavirus pathogenesis and antiviral approaches

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