Study of Generated trasgenic mice predominantly expressing T-tropic HIV-1

我们已经产生了转基因小鼠主要表达T-嗜性HIV-1受体，人CD 4和CXCR 4的CD 4阳性T淋巴细胞。研究结果提示，CXCR 4在HIV-1感染和淋巴细胞转运中的双重作用可能协同诱导HIV-1感染和CD 4 + T细胞下降，因此，确定决定逆转录病毒复制的宿主、组织特异性的受体分子对于理解逆转录病毒感染的发病机制是必要的。然而，这些CD 4和CXCR 4双转基因小鼠中的HIV-1复制被发现是严重不稳定的，这限制了小鼠在了解HIV-1体内发病机制的研究中的使用。在感染这些小鼠淋巴样细胞后观察到前病毒的整合前形式，然而发现这些细胞整合到染色体中的效率远低于人细胞（Koito. A.，Nagasawa. T.，铃木公司，松下公司，需要进一步的研究来表征存在屏障的小鼠细胞，并且克服小鼠淋巴细胞对人逆转录病毒感染的抗性的方法可以允许开发将呈现许多明显优点的啮齿动物模型。为了鉴定HTLV-1受体，我们从活化的人PBMC中产生cDNA文库，并将它们包装到逆转录病毒载体中。参与HYLV-1感染的分子的表达克隆正在进行中。

We have generated transgenic mice predominantly expresing T-tropic HIV-1 receptors, human CD4 and CXCR4 on their CD4-positive T lymphocytes. Our data suggest that the dual function of CXCR4 in HIV-1 infection and in lymphocyte trafficking may cooperatvely induce progressive HIV-1 infection and CD4-positive T cell decline in patients.For understanding the pathogenesis of retroviral infection, it is necessary to identify the receptor molecule(s) which determine the host, tissue specificity of retrovirus replication. However, HIV-1 replication in these CD4 and CXCR4 double transgenic mice are found to be severely impared, limiting the use of mice in the studies for understanding the mechanism of HIV-1 pathogenesis in vivo. Preintegration forms of provirus are observed following infection of these mouse lymphoid cells, however the efficiency of integration into the chromosome of these cells were found to be much lower than that of human cell (Koito.A., Nagasawa.T., Suzuki.G., Matsushita.S., manuscript in preparation).Further studies are required to characterize the barrier exist mouse cells, and approaches to overcome the resistance of mouse lymphoid cells to human retrovirus infection may permit developing a rodent model that would present many obvious advantages. For identification of HTLV-1 receptor(s), we have generated cDNA libraries from activated human PBMC and packaged them into the retrovirus vector. Expression cloning of the molecules which involve in HYLV-1 infection is in progress.