Division of Avian Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, PR China.
Virol J. 2011 Dec 21;8:552. doi: 10.1186/1743-422X-8-552.
Avian leukosis virus subgroup J (ALV-J) preferentially induces myeloid leukosis (ML) in meat-type birds. Since 2008, many clinical cases of hemangioma rather than ML have frequently been reported in association with ALV-J infection in Chinese layer flocks.
Three ALV-J strains associated with hemangioma were isolated and their proviral genomic sequences were determined. The three isolates, JL093-1, SD09DP03 and HLJ09MDJ-1, were 7,670, 7,670, and 7,633 nt in length. Their gag and pol genes were well conserved, with identities of 94.5-98.6% and 97.1-99.5%, respectively, with other ALV-J strains at the amino acid level (aa), while the env genes of the three isolates shared a higher aa identity with the env genes of other hemangioma strains than with those of ML strains. Interestingly, two novel 19-bp insertions in the U3 region in the LTR and 5' UTR, most likely derived from other retroviruses, were found in all the three isolates, thereby separately introducing one E2BP binding site in the U3 region in the LTR and RNA polymerase II transcription factor IIB and core promoter motif ten elements in the 5' UTR. Meanwhile, two binding sites in the U3 LTRs of the three isolates for NFAP-1 and AIB REP1 were lost, and a 1-base deletion in the E element of the 3' UTR of JL093-1 and SD09DP03 introduced a binding site for c-Ets-1. In addition to the changes listed above, the rTM of the 3' UTR was deleted in each of the three isolates.
Our study is the first to discovery the coexistence of two novel insertions in the U3 region in the LTR and the 5' UTR of ALV-J associated with hemangioma symptoms, and the transcriptional regulatory elements introduced should be taken into consideration in the occurrence of hemangioma.
禽白血病病毒 J 亚群(ALV-J)优先诱导肉用型鸟类发生髓性白血病(ML)。自 2008 年以来,中国蛋鸡群中 ALV-J 感染与频繁发生的血管瘤病例而非 ML 病例相关。
分离到 3 株与血管瘤相关的 ALV-J 毒株,并测定了其前病毒基因组序列。这 3 株分离株 JL093-1、SD09DP03 和 HLJ09MDJ-1 的长度分别为 7670、7670 和 7633 个核苷酸。它们的 gag 和 pol 基因高度保守,氨基酸水平的同源性分别为 94.5-98.6%和 97.1-99.5%,与其他 ALV-J 株相比。有趣的是,在 LTR 和 5'UTR 的 U3 区发现了两个新的 19 个碱基插入,很可能来源于其他逆转录病毒,这导致在所有 3 个分离株中 LTR 的 U3 区分别引入了一个 E2BP 结合位点和 RNA 聚合酶 II 转录因子 IIB 和核心启动子 motif ten 元件,而在 5'UTR 中分别引入了一个 NFAP-1 和 AIB REP1 的结合位点。同时,3 个分离株的 U3 LTR 中 NFAP-1 和 AIB REP1 的两个结合位点丢失,JL093-1 和 SD09DP03 的 3'UTR 的 E 元件中的 1 个碱基缺失引入了一个 c-Ets-1 结合位点。除了以上变化,3 个分离株的 3'UTR 的 rTM 被删除。
本研究首次发现与血管瘤症状相关的 ALV-J 的 LTR 和 5'UTR 中存在两个新的 U3 区插入,引入的转录调控元件应该在血管瘤的发生中考虑。