PMID- 23077307
OWN - NLM
STAT- MEDLINE
DCOM- 20130225
LR  - 20240407
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 87
IP  - 1
DP  - 2013 Jan
TI  - Attenuation of porcine reproductive and respiratory syndrome virus by molecular 
      breeding of virus envelope genes from genetically divergent strains.
PG  - 304-13
LID - 10.1128/JVI.01789-12 [doi]
AB  - Molecular breeding via DNA shuffling can direct the evolution of viruses with 
      desired traits. By using a positive-strand RNA virus, porcine reproductive and 
      respiratory syndrome virus (PRRSV), as a model, rapid attenuation of the virus 
      was achieved in this study by DNA shuffling of the viral envelope genes from 
      multiple strains. The GP5 envelope genes of 7 genetically divergent PRRSV strains 
      and the GP5-M genes of 6 different PRRSV strains were molecularly bred by DNA 
      shuffling and iteration of the process, and the shuffled genes were cloned into 
      the backbone of a DNA-launched PRRSV infectious clone. Two representative 
      chimeric viruses, DS722 with shuffled GP5 genes and DS5M3 with shuffled GP5-M 
      genes, were rescued and shown to replicate at a lower level and to form smaller 
      plaques in vitro than their parental virus. An in vivo pathogenicity study 
      revealed that pigs infected with the two chimeric viruses had significant 
      reductions in viral-RNA loads in sera and lungs and in gross and microscopic lung 
      lesions, indicating attenuation of the chimeric viruses. Furthermore, pigs 
      vaccinated with the chimeric virus DS722, but not pigs vaccinated with DS5M3, 
      still acquired protection against PRRSV challenge at a level similar to that of 
      the parental virus. Therefore, this study reveals a unique approach through DNA 
      shuffling of viral envelope genes to attenuate a positive-strand RNA virus. The 
      results have important implications for future vaccine development and will 
      generate broad general interest in the scientific community in rapidly 
      attenuating other important human and veterinary viruses.
FAU - Ni, Yan-Yan
AU  - Ni YY
AD  - Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic 
      Institute and State University, Blacksburg, Virginia, USA.
FAU - Opriessnig, Tanja
AU  - Opriessnig T
FAU - Zhou, Lei
AU  - Zhou L
FAU - Cao, Dianjun
AU  - Cao D
FAU - Huang, Yao-Wei
AU  - Huang YW
FAU - Halbur, Patrick G
AU  - Halbur PG
FAU - Meng, Xiang-Jin
AU  - Meng XJ
LA  - eng
SI  - GENBANK/JX044138
SI  - GENBANK/JX044139
SI  - GENBANK/JX050225
SI  - GENBANK/JX069952
SI  - GENBANK/JX069953
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121017
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (RNA, Viral)
RN  - 0 (Viral Envelope Proteins)
RN  - 0 (Virulence Factors)
RN  - 0 (glycoprotein 5, PRRSV)
SB  - IM
MH  - Animals
MH  - *DNA Shuffling
MH  - Lung/pathology/virology
MH  - Molecular Sequence Data
MH  - Plasma/virology
MH  - Porcine Reproductive and Respiratory Syndrome/*pathology/virology
MH  - Porcine respiratory and reproductive syndrome 
      virus/*genetics/*pathogenicity/physiology
MH  - RNA, Viral/genetics
MH  - Sequence Analysis, DNA
MH  - Swine
MH  - Viral Envelope Proteins/*genetics/metabolism
MH  - Viral Load
MH  - Viral Plaque Assay
MH  - Virulence
MH  - Virulence Factors/*genetics/metabolism
MH  - Virus Replication
PMC - PMC3536372
EDAT- 2012/10/19 06:00
MHDA- 2013/02/26 06:00
PMCR- 2013/07/01
CRDT- 2012/10/19 06:00
PHST- 2012/10/19 06:00 [entrez]
PHST- 2012/10/19 06:00 [pubmed]
PHST- 2013/02/26 06:00 [medline]
PHST- 2013/07/01 00:00 [pmc-release]
AID - JVI.01789-12 [pii]
AID - 01789-12 [pii]
AID - 10.1128/JVI.01789-12 [doi]
PST - ppublish
SO  - J Virol. 2013 Jan;87(1):304-13. doi: 10.1128/JVI.01789-12. Epub 2012 Oct 17.