PMID- 16254361
OWN - NLM
STAT- MEDLINE
DCOM- 20060127
LR  - 20181113
IS  - 0022-538X (Print)
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Linking)
VI  - 79
IP  - 22
DP  - 2005 Nov
TI  - Noncytopathogenic pestivirus strains generated by nonhomologous RNA 
      recombination: alterations in the NS4A/NS4B coding region.
PG  - 14261-70
AB  - Several studies have demonstrated that cytopathogenic (cp) pestivirus strains 
      evolve from noncytopathogenic (noncp) viruses by nonhomologous RNA recombination. 
      In addition, two recent reports showed the rapid emergence of noncp Bovine viral 
      diarrhea virus (BVDV) after a few cell culture passages of cp BVDV strains by 
      homologous recombination between identical duplicated viral sequences. To allow 
      the identification of recombination sites from noncp BVDV strains that evolve 
      from cp viruses, we constructed the cp BVDV strains CP442 and CP552. Both harbor 
      duplicated viral sequences of different origin flanking the cellular insertion 
      Nedd8*; the latter is a prerequisite for their cytopathogenicity. In contrast to 
      the previous studies, isolation of noncp strains was possible only after 
      extensive cell culture passages of CP442 and CP552. Sequence analysis of 15 
      isolated noncp BVDVs confirmed that all recombinant strains lack at least most of 
      Nedd8*. Interestingly, only one strain resulted from homologous recombination 
      while the other 14 strains were generated by nonhomologous recombination. 
      Accordingly, our data suggest that the extent of sequence identity between 
      participating sequences influences both frequency and mode (homologous versus 
      nonhomologous) of RNA recombination in pestiviruses. Further analyses of the 
      noncp recombinant strains revealed that a duplication of 14 codons in the BVDV 
      nonstructural protein 4B (NS4B) gene does not interfere with efficient viral 
      replication. Moreover, an insertion of viral sequences between the NS4A and NS4B 
      genes was well tolerated. These findings thus led to the identification of two 
      genomic loci which appear to be suited for the insertion of heterologous 
      sequences into the genomes of pestiviruses and related viruses.
FAU - Gallei, Andreas
AU  - Gallei A
AD  - Institut fur Virologie, Justus-Liebig-Universitat, Frankfurter Strasse 107, 
      D-35392 Giessen, Germany.
FAU - Orlich, Michaela
AU  - Orlich M
FAU - Thiel, Heinz-Juergen
AU  - Thiel HJ
FAU - Becher, Paul
AU  - Becher P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (DNA Primers)
RN  - 0 (NS4A protein, flavivirus)
RN  - 0 (NS4B protein, flavivirus)
RN  - 0 (RNA, Viral)
RN  - 0 (Viral Nonstructural Proteins)
SB  - IM
MH  - Animals
MH  - Cattle
MH  - Cell Line
MH  - DNA Primers
MH  - Diarrhea Viruses, Bovine Viral/genetics
MH  - Gene Duplication
MH  - Kidney
MH  - Pestivirus/*genetics/growth & development/pathogenicity
MH  - RNA, Viral/*genetics
MH  - *Recombination, Genetic
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Viral Nonstructural Proteins/*genetics
MH  - Viral Plaque Assay
PMC - PMC1280241
EDAT- 2005/10/29 09:00
MHDA- 2006/01/28 09:00
PMCR- 2005/11/01
CRDT- 2005/10/29 09:00
PHST- 2005/10/29 09:00 [pubmed]
PHST- 2006/01/28 09:00 [medline]
PHST- 2005/10/29 09:00 [entrez]
PHST- 2005/11/01 00:00 [pmc-release]
AID - 79/22/14261 [pii]
AID - 1451-05 [pii]
AID - 10.1128/JVI.79.22.14261-14270.2005 [doi]
PST - ppublish
SO  - J Virol. 2005 Nov;79(22):14261-70. doi: 10.1128/JVI.79.22.14261-14270.2005.