PMID- 36669328
OWN - NLM
STAT- MEDLINE
DCOM- 20230206
LR  - 20230504
IS  - 1096-0341 (Electronic)
IS  - 0042-6822 (Linking)
VI  - 579
DP  - 2023 Feb
TI  - Application of codon pair deoptimization for ORF7-induced attenuation of type I 
      porcine reproductive and respiratory syndrome virus without reduced immune 
      responses.
PG  - 119-127
LID - S0042-6822(23)00009-0 [pii]
LID - 10.1016/j.virol.2023.01.009 [doi]
AB  - Codon pair deoptimization (CPD) attenuated type I porcine reproductive and 
      respiratory syndrome virus (PRRSV). Infectious clones covering the full genome of 
      a Korean type I PRRSV (E38) were synthesized, and CPD induced nine synonymous 
      mutants of NSP1 (n = 1) and ORF7 (n = 8). In a trial to rescue live viruses from 
      infectious clones, only four clones with mutations at nt 177 downstream of ORF7 
      were rescued, which showed a substantial decrease in cellular replication 
      ability. The rescue-failed clones had two common mutation sites with a high 
      minimum free energy and significantly modified RNA secondary structure relative 
      to the original virus. In infected pigs, CPD viruses demonstrated significantly 
      lower replication ability and pathogenicity than the original virus. However, 
      immune response level induced by the attenuated viruses and the original virus 
      was similar. This is the first study to demonstrate that type I PRRSV virulence 
      can be attenuated through CPD application to ORF7.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Cha, Sang-Ho
AU  - Cha SH
AD  - PRRS Research Laboratory, Viral Diseases Division, Animal and Plant Quarantine 
      Agency, Gimcheon, 39660, Republic of Korea.
FAU - You, Su-Hwa
AU  - You SH
AD  - PRRS Research Laboratory, Viral Diseases Division, Animal and Plant Quarantine 
      Agency, Gimcheon, 39660, Republic of Korea.
FAU - Lee, Min-A
AU  - Lee MA
AD  - PRRS Research Laboratory, Viral Diseases Division, Animal and Plant Quarantine 
      Agency, Gimcheon, 39660, Republic of Korea.
FAU - Baek, Jong-Hyuk
AU  - Baek JH
AD  - Department of Animal Vaccine Development, BioPOA, 593-26 Dongtangiheung-ro, 
      Hwaseong-si, Gyeonggi-do, Republic of Korea.
FAU - Cho, Sun-Hee
AU  - Cho SH
AD  - Department of Animal Vaccine Development, BioPOA, 593-26 Dongtangiheung-ro, 
      Hwaseong-si, Gyeonggi-do, Republic of Korea.
FAU - Jeong, Jiwoon
AU  - Jeong J
AD  - Division of Animal Care, Yonam College, 313, Yeonam-ro, Seonghwan-eup, Seobuk-gu, 
      Cheonan-si, Chungcheongnam-do, Republic of Korea.
FAU - Park, Chang-Joo
AU  - Park CJ
AD  - Department of Microbiology and Immunology, Eulji University School of Medicine, 
      Yongdu-dong, Jung-gu, Daejeon, Republic of Korea.
FAU - Lee, Myung-Shin
AU  - Lee MS
AD  - Department of Microbiology and Immunology, Eulji University School of Medicine, 
      Yongdu-dong, Jung-gu, Daejeon, Republic of Korea.
FAU - Park, Changhoon
AU  - Park C
AD  - Department of Microbiology and Immunology, Eulji University School of Medicine, 
      Yongdu-dong, Jung-gu, Daejeon, Republic of Korea. Electronic address: 
      votongnum@naver.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230114
PL  - United States
TA  - Virology
JT  - Virology
JID - 0110674
RN  - 0 (Codon)
RN  - 0 (Viral Vaccines)
SB  - IM
MH  - Animals
MH  - Swine
MH  - *Porcine respiratory and reproductive syndrome virus/genetics
MH  - Virus Replication/genetics
MH  - Codon
MH  - Mutation
MH  - *Viruses/genetics
MH  - Immunity
MH  - *Porcine Reproductive and Respiratory Syndrome/genetics
MH  - *Viral Vaccines/genetics
OTO - NOTNLM
OT  - Codon pair deoptimization
OT  - Minimum free energy
OT  - Mutations
OT  - Type I porcine Reproductive respiratory syndrome virus
OT  - Vaccine
COIS- Declaration of competing interest The authors declare that they have no conflict 
      of interests.
EDAT- 2023/01/21 06:00
MHDA- 2023/02/07 06:00
CRDT- 2023/01/20 18:10
PHST- 2022/09/26 00:00 [received]
PHST- 2022/12/11 00:00 [revised]
PHST- 2023/01/11 00:00 [accepted]
PHST- 2023/01/21 06:00 [pubmed]
PHST- 2023/02/07 06:00 [medline]
PHST- 2023/01/20 18:10 [entrez]
AID - S0042-6822(23)00009-0 [pii]
AID - 10.1016/j.virol.2023.01.009 [doi]
PST - ppublish
SO  - Virology. 2023 Feb;579:119-127. doi: 10.1016/j.virol.2023.01.009. Epub 2023 Jan 
      14.