ArticleJournal of virology2005
Resuscitating mutations in a furin cleavage-deficient mutant of the flavivirus tick-borne encephalitis virus.
Article in Journal of virology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- Hiding in plain sight: Genomic and phenotypic characterization of mosquito-borne Bussuquara virus.PLoS neglected tropical diseases · 2025Article
- pr-independent biogenesis of infectious mature Zika virus particles.bioRxiv : the preprint server for biology · 2024Article
- Key Residue in the Precursor Region of M Protein Contributes to the Neurovirulence and Neuroinvasiveness of the African Lineage of Zika Virus.Journal of virology · 2023Article
- Increased Cleavage of Japanese Encephalitis Virus prM Protein Promotes Viral Replication but Attenuates Virulence.Microbiology spectrum · 2022Article
- Neuroinvasiveness of the MR766 strain of Zika virus in IFNAR-/- mice maps to prM residues conserved amongst African genotype viruses.PLoS pathogens · 2021Article
- Review
- Article
- Tick-Borne Encephalitis Virus: A Structural View.Viruses · 2018Review
- Article
- Article
- The role of viral persistence in flavivirus biology.Pathogens and disease · 2014Review
- Immature dengue virus is infectious in human immature dendritic cells via interaction with the receptor molecule DC-SIGN.PloS one · 2014Article
- The Fc region of an antibody impacts the neutralization of West Nile viruses in different maturation states.Journal of virology · 2013Article
- Article
- The infectivity of prM-containing partially mature West Nile virus does not require the activity of cellular furin-like proteases.Journal of virology · 2011Article
- prM-antibody renders immature West Nile virus infectious in vivo.The Journal of general virology · 2011Article
- Article
- Immature dengue virus: a veiled pathogen?PLoS pathogens · 2010Article
- A trans-complementing recombination trap demonstrates a low propensity of flaviviruses for intermolecular recombination.Journal of virology · 2010Article
- Changing the protease specificity for activation of a flavivirus, tick-borne encephalitis virus.Journal of virology · 2008Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cleavage of the viral surface protein prM by the proprotein convertase furin is a key step in the maturation process of flavivirus particles. A mutant of tick-borne encephalitis virus (TBEV) carrying a deletion mutation within the furin recognition motif of protein prM (changing R-T-R-R to R-T-R) was previously shown to be noninfectious in BHK-21 cells. We now demonstrate how natural selection can overcome this lethal defect in two different growth systems by distinct resuscitating mutations. In BHK-21 cells, a spontaneous codon duplication created a minimal furin cleavage motif (R-R-T-R). This mutation restored infectivity by enabling intracellular prM cleavage. A completely different mutation pattern was observed when the mutant virus was passaged in mouse brains. The "pr" part of protein prM, which is removed by cleavage, contains six conserved Cys residues. The mutations selected in mice changed the number of Cys residues to five or seven by substitution mutations near the original cleavage site, probably causing a major perturbation of the structural integrity of protein prM. Although viable in mice, such Cys mutants could not be passaged in BHK-21 cells under normal growth conditions (37 degrees C), but one of the mutants exhibited a low level of infectivity at a reduced incubation temperature (28 degrees C). No evidence for the cleavage of protein prM in BHK-21 cells was obtained. This suggests that under certain growth conditions, the structural perturbation of protein prM can restore the infectivity of TBEV by circumventing the need for intracellular furin-mediated cleavage. This is the first example of a flavivirus using such a molecular mechanism.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.