کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5821806 | 1557817 | 2016 | 5 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Detection of treatment-resistant infectious HIV after genome-directed antiviral endonuclease therapy
ترجمه فارسی عنوان
تشخیص ایدز عفونی مقاوم به درمان پس از درمان انتونوکلئاز ضد ویروسی با ژنوم
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کلمات کلیدی
نیکلاز انگشت روی، آندونوکراسی، مقاومت، ترانسفرکتازی معکوس،
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ویروس شناسی
چکیده انگلیسی
Incurable chronic viral infections are a major cause of morbidity and mortality worldwide. One potential approach to cure persistent viral infections is via the use of targeted endonucleases. Nevertheless, a potential concern for endonuclease-based antiviral therapies is the emergence of treatment resistance. Here we detect for the first time an endonuclease-resistant infectious virus that is found with high frequency after antiviral endonuclease therapy. While testing the activity of HIV pol-specific zinc finger nucleases (ZFNs) alone or in combination with three prime repair exonuclease 2 (Trex2), we identified a treatment-resistant and infectious mutant virus that was derived from a ZFN-mediated disruption of reverse transcriptase (RT). Although gene disruption of HIV protease, RT and integrase could inhibit viral replication, a chance single amino acid insertion within the thumb domain of RT produced a virus that could actively replicate. The endonuclease-resistant virus could replicate in primary CD4+ T cells, but remained susceptible to treatment with antiretroviral RT inhibitors. When secondary ZFN-derived mutations were introduced into the mutant virus's RT or integrase domains, replication could be abolished. Our observations suggest that caution should be exercised during endonuclease-based antiviral therapies; however, combination endonuclease therapies may prevent the emergence of resistance.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Antiviral Research - Volume 126, February 2016, Pages 90-98
Journal: Antiviral Research - Volume 126, February 2016, Pages 90-98
نویسندگان
Harshana S. De Silva Feelixge, Daniel Stone, Harlan L. Pietz, Pavitra Roychoudhury, Alex L. Greninger, Joshua T. Schiffer, Martine Aubert, Keith R. Jerome,