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.

Development and Application of a Multiplex PCR Method for Rapid Differential Detection of Subgroup A, B, and J Avian Leukosis Viruses

“…Coinfection, which may have a more powerful pathogenicity and which brings about more serious economic losses, has become widespread among flocks in China (40). Furthermore, coinfection with different subgroups provides the opportunity for the recombination of ALVs and makes it possible for the emergence of new subgroup viruses, such as ALV-J, with stronger pathogenicity and epidemicity (8,31). Therefore, achieving rapid clinical detection of infection is imperative for the effective control of the spread of ALVs (41).…”

“…ALVs are divided into exogenous viruses (ALV-A, -B, -C, -D, and -J) and endogenous viruses (ALV-E) according to sequence differences in their long terminal repeats (LTRs) (23). The gag genes encode Gag (group-specific antigen), the pol genes encode reverse transcriptase and integrase, and the env gene encodes the envelope glycoproteins (2,31). The pol genes show Ͼ96% sequence identity among the exogenous ALVs (32).…”

Identification of a novel B-cell epitope specific for avian leukosis virus subgroup J gp85 protein

“…The mouse anti-ALV-J gp85 serum was The chicken anti-ALV-J serum was obtained from a chicken infected with ALV-J (HLJ09SH01 strain) [28]. The ELISA results indicated that the identified epitope peptide 134 AEAELRDFI 142 was recognized by both of these antisera (Fig.…”

Avian leukosis virus subgroup J induces VEGF expression via NF-κB/PI3K-dependent IL-6 production

“…IL-6 is a multifunctional cytokine with central roles in immune and inflammatory reactions, as well as in cancer development [20-24]. IL-6 plays an important role in host immune system, wherein it has been considered to facilitate elimination of pathogens during virus-host interactions.…”