title: A 205-nucleotide deletion in the 3' untranslated region of avian leukosis virus subgroup J, currently emergent in China, contributes to its pathogenicity.
abstract: In the past 5 years, an atypical clinical outbreak of avian leukosis virus subgroup J (ALV-J), which contains a unique 205-nucleotide deletion in its 3' untranslated region (3'UTR), has become epidemic in chickens in China. To determine the role of the 205-nucleotide deletion in the pathogenicity of ALV-J, a pair of viruses were constructed and rescued. The first virus was an ALV-J Chinese isolate (designated HLJ09SH01) containing the 205-nucleotide deletion in its 3'UTR. The second virus was a chimeric clone in which the 3'UTR contains a 205-nucleotide sequence corresponding to a region of the ALV-J prototype virus. The replication and pathogenicity of the rescued viruses (rHLJ09SH01 and rHLJ09SH01A205) were investigated. Compared to rHLJ09SH01A205, rHLJ09SH01 showed a moderate growth advantage in vitro and in vivo, in addition to exhibiting a higher oncogenicity rate and lethality rate in layers and broilers. Increased vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth receptor subtype 2 (VEGFR-2) expression was induced by rHLJ09SH01 more so than by rHLJ09SH01A205 during early embryonic vascular development, but this increased expression disappeared when the expression levels were normalized to the viral levels. This finding suggests that the expression of VEGF-A and VEGFR-2 is associated with viral replication and may also represent a novel molecular mechanism underlying the oncogenic potential of ALV-J. Overall, our findings not only indicate that the unique 205-nucleotide deletion in the ALV-J genome occurred naturally in China and contributes to increased pathogenicity but also point to the possible mechanism of ALV-J-induced oncogenicity.
authors.affiliation: Division of Avian Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Yulong
authors.initials: Y
authors.lastname: Gao
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Wang
authors.forename: Liting
authors.initials: L
authors.lastname: Qin
authors.forename: Xiaole
authors.initials: X
authors.lastname: Qi
authors.forename: Yue
authors.initials: Y
authors.lastname: Qu
authors.forename: Honglei
authors.initials: H
authors.lastname: Gao
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D000818:Animals; D001353:Avian Leukosis / Q000453:epidemiology* / Q000235:genetics; D001354:Avian Leukosis Virus / Q000235:genetics* / Q000472:pathogenicity*; D001483:Base Sequence; D002645:Chickens; D002681:China / Q000453:epidemiology; D016000:Cluster Analysis; D021821:Communicable Diseases, Emerging / Q000453:epidemiology* / Q000821:virology; D019295:Computational Biology; D017931:DNA Primers / Q000235:genetics; D008969:Molecular Sequence Data; D010802:Phylogeny; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D014774:Virulence / Q000235:genetics; D014779:Virus Replication / Q000235:genetics / Q000502:physiology
chemical_list: D020413:3' Untranslated Regions; D017931:DNA Primers; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2