Chakraborty Joana, Okonta Henry, Bagalb Hussein, Lee Soon Jin, Fink Brian, Changanamkandat Rajesh, Duggan Joan
Department of Physiology and Pharmacology, College of Medicine, Health Science Campus, University of Toledo, 3000 Arlington Avenue, Toledo, OH 43614, USA.
Virology. 2008 Jul 20;377(1):100-9. doi: 10.1016/j.virol.2008.04.008. Epub 2008 May 27.
We have demonstrated breast milk transmitted MoMuLV-ts1 retrovirus infection and subsequent lymphoma development in offspring of uninfected mothers suckled by infected surrogate mothers. Additionally, we have shown that the lymphoma development occurs as a result of viral gene integration into host genome. A total of 146 pups from Balb/C mice were divided into 5 groups; one control and 4 experimental. All offspring suckled from surrogate infected or control mothers, except one group of infected pups left with their biological mothers. Thirteen of 91 infected pups developed lymphoma. Inverse-PCR, DNA cloning, and quantitative real-time PCR (qRT-PCR) were used to study the virus integration sites (VIS) and alterations in gene expression. VIS were randomly distributed throughout the genome. The majority of insertion sites were found in chromosomes 10, 12 and 13. A total of 209 proviral genomic insertion sites were located with 52 intragenic and 157 intergenic sites. We have identified 29 target genes. Four genes including Tacc3, Aurka, Gfi1 and Ahi1 showed the maximum upregulation of mRNA expression. These four genes can be considered as candidate genes based on their association with cancer. Upregulation of these genes may be involved in this type of lymphoma development. This model provides an important opportunity to gain insight into the relationship of viral gene insertion into host genome and development of lymphoma via natural transmission route such as breast milk.
我们已经证明，未感染的母亲所生的后代，由感染的代孕母亲哺乳，会通过母乳感染莫洛尼鼠白血病病毒ts1（MoMuLV-ts1）逆转录病毒，并随后发生淋巴瘤。此外，我们还表明，淋巴瘤的发生是病毒基因整合到宿主基因组的结果。将来自Balb/C小鼠的146只幼崽分为5组；一组为对照组，4组为实验组。除了一组感染的幼崽由其亲生母亲哺育外，所有后代均由感染或未感染的代孕母亲哺乳。91只感染的幼崽中有13只发生了淋巴瘤。采用反向PCR、DNA克隆和定量实时PCR（qRT-PCR）研究病毒整合位点（VIS）和基因表达的变化。VIS随机分布于整个基因组中。大多数插入位点位于10号、12号和13号染色体上。共定位了209个前病毒基因组插入位点，其中52个位于基因内，157个位于基因间。我们鉴定出了29个靶基因。包括Tacc3、Aurka、Gfi1和Ahi1在内的四个基因显示出mRNA表达的最大上调。基于它们与癌症的关联，这四个基因可被视为候选基因。这些基因的上调可能与这种类型的淋巴瘤发生有关。该模型为深入了解病毒基因插入宿主基因组与通过母乳等自然传播途径发生淋巴瘤之间的关系提供了一个重要机会。
