A chimeric vaccine displaying the prM-E proteins of the Australian genotype IV strain of Japanese encephalitis virus protects mice against lethal challenge DOI Creative Commons
Jessica J. Harrison, Wilson Nguyen, Mahali S. Morgan

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 3, 2023

Abstract In 2022, a genotype IV (GIV) strain of Japanese encephalitis virus caused an unprecedented and widespread outbreak disease in pigs humans Australia. As no veterinary vaccines against JEV are approved Australia all current human derived from (G) III strains, we used the recently described insect-specific Binjari (BinJV) chimeric flavivirus vaccine technology to produce GIV candidate. Herein describe production displaying structural prM E proteins isolate obtained stillborn piglet (JEV NSW/22 ) genomic backbone BinJV (BinJ/JEV NSW/22- prME). BinJ/JEV prME was shown be antigenically indistinguishable parental by K D analysis panel JEV-reactive monoclonal antibodies ELISA. replicated efficiently C6/36 cells, reaching titres 10 8 infectious units/mL - important attribute for manufacture. expected, failed replicate variety vertebrate cells lines. When immunise mice, induced potent neutralising response JEVNSW/22 GII GIII strains. The provided complete protection lethal challenge with , whilst also providing partial viraemia related Murray Valley virus. Our results demonstrate that is promising candidate JEV.

Language: Английский

TMEM106B-mediated SARS-CoV-2 infection allows for robust ACE2-independent infection in vitro but not in vivo DOI Creative Commons
Kexin Yan, Troy Dumenil, Romal Stewart

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(11), P. 114921 - 114921

Published: Nov. 1, 2024

Angiotensin-converting enzyme 2 (ACE2) is the primary entry receptor for severe acute respiratory syndrome coronavirus (SARS-CoV-2), but ACE2-independent has been observed in vitro strains with spike-E484D substitution. Here, we conduct a whole-genome CRISPR-Cas9 knockout screen using SARS-CoV-2 mouse adapted 1 (SARS-CoV-2

Language: Английский

Citations

5
TMEM106B-mediated SARS-CoV-2 infection allows for robust ACE2-independent infection in vitro but not in vivo DOI Creative Commons
Kexin Yan, Troy Dumenil, Romal Stewart

et al.

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

Published: May 8, 2024

ABSTRACT Angiotensin converting enzyme 2 (ACE2) serves as the primary entry receptor for severe acute respiratory syndrome coronavirus (SARS-CoV-2). However, ACE2-independent has been observed in vitro SARS-CoV-2 strains containing E484D amino acid substitution spike protein. In this study, we conducted a whole genome CRISPR-Cas9 knockout screen using strain spike-E484D (SARS-CoV-2 MA1 ) to identify mechanisms. Our findings revealed that infection HEK293T cells relied on heparan sulfate and endocytic pathways, with TMEM106B emerging most significant contributor. While productively infected human brain organoids K18-hACE2 mouse brains, it did not infect C57BL/6J or Ifnar -/- brains. This suggests via TMEM106B, which is protein predominantly expressed brain, overtly increase risk of neuroinvasiveness wild-type mice. Importantly, replicate Ace2 tracts. Overall, robust by likely phenomenon specific conditions, no apparent clinical implications.

Language: Английский

Citations

1
TMEM106B-Mediated SARS-CoV-2 Infection Allows for Robust ACE2-Independent Infection in vitro but Not in vivo DOI
Kexin Yan, Troy Dumenil, Romal Stewart

et al.

Published: Jan. 1, 2024

Angiotensin converting enzyme 2 (ACE2) serves as the primary entry receptor for severe acute respiratory syndrome coronavirus (SARS-CoV-2). However, ACE2-independent has been observed in vitro SARS-CoV-2 strains containing E484D amino acid substitution spike protein. Herein, we conducted a whole genome CRISPR-Cas9 knockout screen using strain spike-E484D (SARS-CoV-2MA1) to identify mechanisms. Our findings revealed that SARS-CoV-2MA1 infection HEK293T cells relied on heparan sulfate and endocytic pathways, with TMEM106B, transmembrane lysosomal protein, emerging most significant contributor. While productively infected human brain organoids K18-hACE2 mouse brains, it did not infect C57BL/6J or Ifnar-/- brains. This suggests via which is protein predominantly expressed brain, overtly increase risk of neuroinvasiveness mice endogenous Ace2 expression. Importantly, replicate Ace2-/- tracts. Overall, this robust by SARS-CoV-2E484D likely an phenomenon, no apparent implications infections vivo.

Language: Английский

Citations

0
A chimeric vaccine displaying the prM-E proteins of the Australian genotype IV strain of Japanese encephalitis virus protects mice against lethal challenge DOI Creative Commons
Jessica J. Harrison, Wilson Nguyen, Mahali S. Morgan

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 3, 2023

Abstract In 2022, a genotype IV (GIV) strain of Japanese encephalitis virus caused an unprecedented and widespread outbreak disease in pigs humans Australia. As no veterinary vaccines against JEV are approved Australia all current human derived from (G) III strains, we used the recently described insect-specific Binjari (BinJV) chimeric flavivirus vaccine technology to produce GIV candidate. Herein describe production displaying structural prM E proteins isolate obtained stillborn piglet (JEV NSW/22 ) genomic backbone BinJV (BinJ/JEV NSW/22- prME). BinJ/JEV prME was shown be antigenically indistinguishable parental by K D analysis panel JEV-reactive monoclonal antibodies ELISA. replicated efficiently C6/36 cells, reaching titres 10 8 infectious units/mL - important attribute for manufacture. expected, failed replicate variety vertebrate cells lines. When immunise mice, induced potent neutralising response JEVNSW/22 GII GIII strains. The provided complete protection lethal challenge with , whilst also providing partial viraemia related Murray Valley virus. Our results demonstrate that is promising candidate JEV.

Language: Английский

Citations

0