A Triple Amino Acid Substitution at Position 88/94/95 in Glycoprotein GP2a of Type 1 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV1) Is Responsible for Adaptation to MARC-145 Cells

Jiexiong Xie; Ivan Trus; Dayoung Oh; Lise Kirstine Kvisgaard; Julie C F Rappe; Nicolas Ruggli; Nathalie Vanderheijden; Lars Erik Larsen; François Lefèvre; Hans J Nauwynck

doi:10.3390/v11010036

A Triple Amino Acid Substitution at Position 88/94/95 in Glycoprotein GP2a of Type 1 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV1) Is Responsible for Adaptation to MARC-145 Cells

Jiexiong Xie
, Ivan Trus
, Dayoung Oh
, Lise Kirstine Kvisgaard
, Julie C F Rappe
, Nicolas Ruggli
, Nathalie Vanderheijden
, Lars Erik Larsen
, François Lefèvre
, Hans J Nauwynck^*

^*Corresponding author for this work

Ghent University
University of Bern
INRAE

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

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Abstract

The Meat Animal Research Center-145 (MARC-145) cell line has been proven to be valuable for viral attenuation regarding vaccine development and production. Cell-adaptation is necessary for the efficient replication of porcine reproductive and respiratory syndrome virus (PRRSV) in these cells. Multiple sequence analysis revealed consistent amino acid substitutions in GP2a (V88F, M94I, F95L) of MARC-145 cell-adapted strains. To investigate the putative effect of these substitutions, mutations at either position 88, 94, 95, and their combinations were introduced into two PRRSV1 (13V091 and IVI-1173) infectious clones followed by the recovery of viable recombinants. When comparing the replication kinetics in MARC-145 cells, a strongly positive effect on the growth characteristics of the 13V091 strain (+2.1 log10) and the IVI-1173 strain (+1.7 log10) compared to wild-type (WT) virus was only observed upon triple amino acid substitution at positions 88 (V88F), 94 (M94I), and 95 (F95L) of GP2a, suggesting that the triple mutation is a determining factor in PRRSV1 adaptation to MARC-145 cells.

Original language	English
Article number	36
Journal	Viruses
Volume	11
Issue number	1
Number of pages	17
ISSN	1999-4915
DOIs	https://doi.org/10.3390/v11010036
Publication status	Published - 2019

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SDG 3 Good Health and Well-being

Keywords

GP2a
MARC-145
PRRSV
adaptation mutation

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10.3390/v11010036

Viruses 11 00036Final published version, 4.57 MB

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Xie, J., Trus, I., Oh, D., Kvisgaard, L. K., Rappe, J. C. F., Ruggli, N., Vanderheijden, N., Larsen, L. E., Lefèvre, F., & Nauwynck, H. J. (2019). A Triple Amino Acid Substitution at Position 88/94/95 in Glycoprotein GP2a of Type 1 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV1) Is Responsible for Adaptation to MARC-145 Cells. Viruses, 11(1), Article 36. https://doi.org/10.3390/v11010036

@article{9eb384223a9049819c15f9d056e8477f,

title = "A Triple Amino Acid Substitution at Position 88/94/95 in Glycoprotein GP2a of Type 1 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV1) Is Responsible for Adaptation to MARC-145 Cells",

abstract = "The Meat Animal Research Center-145 (MARC-145) cell line has been proven to be valuable for viral attenuation regarding vaccine development and production. Cell-adaptation is necessary for the efficient replication of porcine reproductive and respiratory syndrome virus (PRRSV) in these cells. Multiple sequence analysis revealed consistent amino acid substitutions in GP2a (V88F, M94I, F95L) of MARC-145 cell-adapted strains. To investigate the putative effect of these substitutions, mutations at either position 88, 94, 95, and their combinations were introduced into two PRRSV1 (13V091 and IVI-1173) infectious clones followed by the recovery of viable recombinants. When comparing the replication kinetics in MARC-145 cells, a strongly positive effect on the growth characteristics of the 13V091 strain (+2.1 log10) and the IVI-1173 strain (+1.7 log10) compared to wild-type (WT) virus was only observed upon triple amino acid substitution at positions 88 (V88F), 94 (M94I), and 95 (F95L) of GP2a, suggesting that the triple mutation is a determining factor in PRRSV1 adaptation to MARC-145 cells.",

keywords = "GP2a, MARC-145, PRRSV, adaptation mutation",

author = "Jiexiong Xie and Ivan Trus and Dayoung Oh and Kvisgaard, \{Lise Kirstine\} and Rappe, \{Julie C F\} and Nicolas Ruggli and Nathalie Vanderheijden and Larsen, \{Lars Erik\} and Fran{\c c}ois Lef{\`e}vre and Nauwynck, \{Hans J\}",

year = "2019",

doi = "10.3390/v11010036",

language = "English",

volume = "11",

journal = "Viruses",

issn = "1999-4915",

publisher = "M D P I AG",

number = "1",

}

Xie, J, Trus, I, Oh, D, Kvisgaard, LK, Rappe, JCF, Ruggli, N, Vanderheijden, N, Larsen, LE, Lefèvre, F & Nauwynck, HJ 2019, 'A Triple Amino Acid Substitution at Position 88/94/95 in Glycoprotein GP2a of Type 1 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV1) Is Responsible for Adaptation to MARC-145 Cells', Viruses, vol. 11, no. 1, 36. https://doi.org/10.3390/v11010036

A Triple Amino Acid Substitution at Position 88/94/95 in Glycoprotein GP2a of Type 1 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV1) Is Responsible for Adaptation to MARC-145 Cells. / Xie, Jiexiong; Trus, Ivan; Oh, Dayoung et al.
In: Viruses, Vol. 11, No. 1, 36, 2019.

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

TY - JOUR

T1 - A Triple Amino Acid Substitution at Position 88/94/95 in Glycoprotein GP2a of Type 1 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV1) Is Responsible for Adaptation to MARC-145 Cells

AU - Xie, Jiexiong

AU - Trus, Ivan

AU - Oh, Dayoung

AU - Kvisgaard, Lise Kirstine

AU - Rappe, Julie C F

AU - Ruggli, Nicolas

AU - Vanderheijden, Nathalie

AU - Larsen, Lars Erik

AU - Lefèvre, François

AU - Nauwynck, Hans J

PY - 2019

Y1 - 2019

N2 - The Meat Animal Research Center-145 (MARC-145) cell line has been proven to be valuable for viral attenuation regarding vaccine development and production. Cell-adaptation is necessary for the efficient replication of porcine reproductive and respiratory syndrome virus (PRRSV) in these cells. Multiple sequence analysis revealed consistent amino acid substitutions in GP2a (V88F, M94I, F95L) of MARC-145 cell-adapted strains. To investigate the putative effect of these substitutions, mutations at either position 88, 94, 95, and their combinations were introduced into two PRRSV1 (13V091 and IVI-1173) infectious clones followed by the recovery of viable recombinants. When comparing the replication kinetics in MARC-145 cells, a strongly positive effect on the growth characteristics of the 13V091 strain (+2.1 log10) and the IVI-1173 strain (+1.7 log10) compared to wild-type (WT) virus was only observed upon triple amino acid substitution at positions 88 (V88F), 94 (M94I), and 95 (F95L) of GP2a, suggesting that the triple mutation is a determining factor in PRRSV1 adaptation to MARC-145 cells.

AB - The Meat Animal Research Center-145 (MARC-145) cell line has been proven to be valuable for viral attenuation regarding vaccine development and production. Cell-adaptation is necessary for the efficient replication of porcine reproductive and respiratory syndrome virus (PRRSV) in these cells. Multiple sequence analysis revealed consistent amino acid substitutions in GP2a (V88F, M94I, F95L) of MARC-145 cell-adapted strains. To investigate the putative effect of these substitutions, mutations at either position 88, 94, 95, and their combinations were introduced into two PRRSV1 (13V091 and IVI-1173) infectious clones followed by the recovery of viable recombinants. When comparing the replication kinetics in MARC-145 cells, a strongly positive effect on the growth characteristics of the 13V091 strain (+2.1 log10) and the IVI-1173 strain (+1.7 log10) compared to wild-type (WT) virus was only observed upon triple amino acid substitution at positions 88 (V88F), 94 (M94I), and 95 (F95L) of GP2a, suggesting that the triple mutation is a determining factor in PRRSV1 adaptation to MARC-145 cells.

KW - GP2a

KW - MARC-145

KW - PRRSV

KW - adaptation mutation

U2 - 10.3390/v11010036

DO - 10.3390/v11010036

M3 - Journal article

C2 - 30626009

SN - 1999-4915

VL - 11

JO - Viruses

JF - Viruses

IS - 1

M1 - 36

ER -

A Triple Amino Acid Substitution at Position 88/94/95 in Glycoprotein GP2a of Type 1 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV1) Is Responsible for Adaptation to MARC-145 Cells

Abstract

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Keywords

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