INTERFERON INHIBITS TRANSFORMATION BY MURINE SARCOMA-VIRUSES BEFORE INTEGRATION OF PROVIRUS

INTERFERON INHIBITS TRANSFORMATION BY MURINE SARCOMA-VIRUSES BEFORE INTEGRATION OF PROVIRUS
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DOI:
10.1038/288093a0
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发表时间:
1980-01-01
期刊:
影响因子:
64.8
通讯作者:
MORRIS, AG
MORRIS, AG
中科院分区:
综合性期刊1区
文献类型:
--
作者:
AVERY, RJ;NORTON, JD;MORRIS, AG

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c型逆转录病毒的肿瘤转化需要合成RNA基因组的DNA拷贝(原病毒)并将其整合到宿主细胞DNA中。干扰素(IFN)能稳定地阻止小鼠肉瘤病毒(KiMSV)和小鼠白血病病毒(MLV)对小鼠成纤维细胞的转化。细胞克隆(IFN克隆),在IFN (104 U ml-1)存在下从NIH-3T3[小鼠成纤维细胞]细胞培养物中分离出来,这些细胞用IFN处理,然后在每个细胞都被感染的条件下感染KiMSV (KiMLV),表型上未转化。这些未转化的细胞不产生病毒或含有可拯救的KiMSV。在没有IFN的情况下,用相同的方法分离的细胞被均匀转化,所有细胞都产生KiMSV (KiMLV)或含有可拯救的KiMSV。干扰素阻止原病毒的合成或整合,或者在干扰素存在的情况下,原病毒被整合而不表达。5个有代表性的克隆没有检测到KiMSV原病毒DNA,并且被KiMSV (KiMLV)感染的初始阶段被IFN治疗抑制。干扰素似乎在整合之前起作用,阻止原病毒DNA的合成或整合。
Neoplastic transformation by C-type retroviruses requires synthesis of a DNA copy (the provirus) of the RNA genome and its integration into the host cell DNA. Interferon (IFN) can stably prevent transformation of murine fibroblasts by the Kirsten strain of murine sarcoma virus (KiMSV) and a murine leukemia virus (MLV). Cell clones (IFN clones), isolated in the presence of IFN (104 U ml-1) from cultures of NIH-3T3 [mouse fibroblast] cells which were treated with IFN, and then infected with KiMSV (KiMLV) in conditions where every cell was infected, were phenotypically untransformed. These untransformed cells did not produce virus or contain rescuable KiMSV. Cells isolated using an identical procedure, but in the absence of IFN, were uniformly transformed and all produced KiMSV (KiMLV) or contained rescuable KiMSV. IFN prevents synthesis or integration of the provirus, or else in the presence of IFN the provirus is integrated such that it is not expressed. Five representative clones contain no detectable KiMSV proviral DNA and the initial stages of infection by KiMSV (KiMLV) are inhibited by IFN treatment. IFN seems to act before integration, preventing the synthesis or the integration of proviral DNA.