Identification of plasticity and interactions of a highly conserved motif within a picornavirus capsid precursor required for virus infectivity

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Identification of plasticity and interactions of a highly conserved motif within a picornavirus capsid precursor required for virus infectivity. / Kristensen, Thea; Belsham, Graham J.

In: Scientific Reports, Vol. 9, No. 1, 11747, 2019.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Kristensen, T & Belsham, GJ 2019, 'Identification of plasticity and interactions of a highly conserved motif within a picornavirus capsid precursor required for virus infectivity', Scientific Reports, vol. 9, no. 1, 11747. https://doi.org/10.1038/s41598-019-48170-9

APA

Kristensen, T., & Belsham, G. J. (2019). Identification of plasticity and interactions of a highly conserved motif within a picornavirus capsid precursor required for virus infectivity. Scientific Reports, 9(1), [11747]. https://doi.org/10.1038/s41598-019-48170-9

Vancouver

Kristensen T, Belsham GJ. Identification of plasticity and interactions of a highly conserved motif within a picornavirus capsid precursor required for virus infectivity. Scientific Reports. 2019;9(1). 11747. https://doi.org/10.1038/s41598-019-48170-9

Author

Kristensen, Thea ; Belsham, Graham J. / Identification of plasticity and interactions of a highly conserved motif within a picornavirus capsid precursor required for virus infectivity. In: Scientific Reports. 2019 ; Vol. 9, No. 1.

Bibtex

@article{10aea1ae4fae4b89b2361eef46c2bef3,
title = "Identification of plasticity and interactions of a highly conserved motif within a picornavirus capsid precursor required for virus infectivity",
abstract = "The picornavirus family includes poliovirus (PV) (genus: enterovirus), human rhinoviruses (enterovirus) and foot-and-mouth disease virus (FMDV) (aphthovirus). These are responsible for important human and animal health concerns worldwide including poliomyelitis, the common cold and foot-and-mouth disease (FMD) respectively. In picornavirus particles, the positive-sense RNA genome (ca. 7–9 kb) is packaged within a protein shell (capsid) usually consisting of three surface exposed proteins, VP1, VP2 and VP3 plus the internal VP4, which are generated following cleavage of the capsid precursor by a virus-encoded protease. We have previously identified a motif near the C-terminus of FMDV VP1 that is required for capsid precursor processing. This motif is highly conserved among other picornaviruses, and is also likely to be important for their capsid precursor processing. We have now determined the plasticity of residues within this motif for virus infectivity and found an important interaction between FMDV residue VP1 R188 within this conserved motif and residue W129 in VP2 that is adjacent in the virus capsid. The FMDV (VP1 R188A) mutant virus has only been rescued with the secondary substitution VP2 W129R. This additional change compensates for the defect resulting from the VP1 R188A substitution and restored both capsid precursor processing and virus viability.",
author = "Thea Kristensen and Belsham, {Graham J.}",
year = "2019",
doi = "10.1038/s41598-019-48170-9",
language = "English",
volume = "9",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "nature publishing group",
number = "1",

}

RIS

TY - JOUR

T1 - Identification of plasticity and interactions of a highly conserved motif within a picornavirus capsid precursor required for virus infectivity

AU - Kristensen, Thea

AU - Belsham, Graham J.

PY - 2019

Y1 - 2019

N2 - The picornavirus family includes poliovirus (PV) (genus: enterovirus), human rhinoviruses (enterovirus) and foot-and-mouth disease virus (FMDV) (aphthovirus). These are responsible for important human and animal health concerns worldwide including poliomyelitis, the common cold and foot-and-mouth disease (FMD) respectively. In picornavirus particles, the positive-sense RNA genome (ca. 7–9 kb) is packaged within a protein shell (capsid) usually consisting of three surface exposed proteins, VP1, VP2 and VP3 plus the internal VP4, which are generated following cleavage of the capsid precursor by a virus-encoded protease. We have previously identified a motif near the C-terminus of FMDV VP1 that is required for capsid precursor processing. This motif is highly conserved among other picornaviruses, and is also likely to be important for their capsid precursor processing. We have now determined the plasticity of residues within this motif for virus infectivity and found an important interaction between FMDV residue VP1 R188 within this conserved motif and residue W129 in VP2 that is adjacent in the virus capsid. The FMDV (VP1 R188A) mutant virus has only been rescued with the secondary substitution VP2 W129R. This additional change compensates for the defect resulting from the VP1 R188A substitution and restored both capsid precursor processing and virus viability.

AB - The picornavirus family includes poliovirus (PV) (genus: enterovirus), human rhinoviruses (enterovirus) and foot-and-mouth disease virus (FMDV) (aphthovirus). These are responsible for important human and animal health concerns worldwide including poliomyelitis, the common cold and foot-and-mouth disease (FMD) respectively. In picornavirus particles, the positive-sense RNA genome (ca. 7–9 kb) is packaged within a protein shell (capsid) usually consisting of three surface exposed proteins, VP1, VP2 and VP3 plus the internal VP4, which are generated following cleavage of the capsid precursor by a virus-encoded protease. We have previously identified a motif near the C-terminus of FMDV VP1 that is required for capsid precursor processing. This motif is highly conserved among other picornaviruses, and is also likely to be important for their capsid precursor processing. We have now determined the plasticity of residues within this motif for virus infectivity and found an important interaction between FMDV residue VP1 R188 within this conserved motif and residue W129 in VP2 that is adjacent in the virus capsid. The FMDV (VP1 R188A) mutant virus has only been rescued with the secondary substitution VP2 W129R. This additional change compensates for the defect resulting from the VP1 R188A substitution and restored both capsid precursor processing and virus viability.

U2 - 10.1038/s41598-019-48170-9

DO - 10.1038/s41598-019-48170-9

M3 - Journal article

C2 - 31409836

AN - SCOPUS:85070763130

VL - 9

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 11747

ER -

ID: 227474746