A novel transcription and replication-competent virus-like particles system modelling the Nipah virus life cycle

Emerging Microbes & Infections, Journal Year: 2024, Volume and Issue: 13(1)

Published: June 12, 2024

Nipah virus (NiV), a highly pathogenic Henipavirus in humans, has been responsible for annual outbreaks recent years. Experiments revolving live NiV are restricted to biosafety level 4 (BSL-4) laboratories, which impedes research. In this study, we developed transcription and replication-competent NiV-like particles (trVLP-NiV) lacking N, P, L genes. This trVLP-NiV exhibited the ability infect continuously passage cells ectopically expressing proteins while maintaining stable genetic characteristics. Moreover, displayed favourable safety profile hamsters. Using system, found nucleoprotein residues interacting with viral RNA backbone affected replication opposite patterns. engineered system was sensitive well-established antiviral drugs, innate host factors, neutralising antibodies. We then established high-throughput screening platform utilizing trVLP-NiV, leading identification of tunicamycin as potential anti-NiV compound. Evidence showed that inhibited by decreasing infectivity progeny virions. conclusion, provided convenient versatile molecular tool investigating biology conducting drug under BSL-2 conditions. Its application will contribute development medical countermeasures against infections.

Language: Английский

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De novo rescue of new henipaviruses under BSL-4 conditions – From sequence to pathogen

Advances in virus research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Indiscriminate activities of different henipavirus polymerase complex proteins allow for efficient minigenome replication in hybrid systems

Journal of Virology, Journal Year: 2024, Volume and Issue: 98(6)

Published: May 23, 2024

ABSTRACT The henipaviruses, including Nipah virus (NiV) and Hendra (HeV), are biosafety level 4 (BSL-4) zoonotic pathogens that cause severe neurological respiratory disease in humans. To study the replication machinery of these viruses, we developed robust minigenome systems can be safely used BSL-2 conditions. nucleocapsid (N), phosphoprotein (P), large protein (L) henipaviruses critical elements their thus essential support components systems. Here, tested effects diverse combinations proteins on capacity NiV HeV minigenomes by exchanging helper plasmids coding for among two viruses. We demonstrate all one or more heterologous were capable replicating both minigenomes. Sequence alignment showed identities 92% N protein, 67% P, 87% L. Notably, variations amino acid residues not concentrated N-P P-L interacting regions implying dissimilarities composition polymerase complex may impact interactions. observed indiscriminate activity is different from related which genomes only when whole belongs to same virus. This newly promiscuous property henipavirus likely attributed conserved interaction could potentially harnessed develop universal anti-henipavirus antivirals. IMPORTANCE Given severity induced viruses humans continuous emergence new as well henipa-like it necessary conduct a comprehensive investigation biology with host. development antiviral agents studied allow experiments performed under 2 (HeV) provide convenient alternative studying replication. Using systems, any combination three effectively initiate viral minigenomes, suggests effective targets interventions.

Language: Английский

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A Comparative Assessment of the Pathogenic Potential of Newly Discovered Henipaviruses

Pathogens, Journal Year: 2024, Volume and Issue: 13(7), P. 587 - 587

Published: July 16, 2024

Recent advances in high-throughput sequencing technologies have led to the discovery of a plethora previously unknown viruses animal samples. Some these newly detected are closely related human pathogens. A prime example henipaviruses. Both Nipah (NiV) and Hendra virus (HeV) cause severe disease humans. Henipaviruses zoonotic origin, hosts, including intermediate play critical role viral transmission The natural reservoir hosts NiV HeV seem be restricted few fruit bat species

Language: Английский

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Indiscriminate activities of different Henipavirus polymerase complex proteins allow for efficient minigenome replication in hybrid systems

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 18, 2024

ABSTRACT The henipaviruses, including Nipah virus (NiV) and Hendra (HeV), are biosafety level 4 (BSL-4) zoonotic pathogens that cause severe neurological respiratory disease in humans. To study the replication machinery of these viruses we developed robust minigenome systems can be safely used BSL-2 conditions. nucleocapsid (N), phosphoprotein (P), large protein (L) henipaviruses critical elements their thus essential support components systems. Here, tested effects diverse combinations proteins on capacity NiV HeV minigenomes by exchanging helper plasmids coding for among two viruses. We demonstrate all one or more heterologous were capable replicating both minigenomes. Sequence alignment showed identities 92% N protein, 67% P, 87% L. Notably, variations amino acid residues not concentrated N-P P-L interacting regions implying dissimilarities composition polymerase complex may impact interactions. observed indiscriminate activity is different from related viruses, which genomes only when whole belongs to same virus. This newly promiscuous property henipavirus could potentially harnessed develop universal anti-henipavirus antivirals. IMPORTANCE Given severity induced humans continuous emergence new as well henipa-like it necessary conduct comprehensive investigation biology interaction with host. development antiviral agents studied allow experiments performed under 2 (HeV) provide a convenient alternative system studying replication. Using systems, any three effectively initiate viral minigenomes, suggest effective targets interventions.

Language: Английский

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