toward the development of a single-round infection assay based on egfp reporting for anti-hiv-1 drug discovery

نویسندگان

mahdieh soezi hepatitis and aids department, pasteur institute of iran, tehran, iran - national institute of genetic engineering and biotechnology, tehran, iran

arash memarnejadian tel: +98 21 66969291; fax: +98 21 66969291

saeed aminzadeh

rezvan zabihollahi hepatitis and aids department, pasteur institute of iran, tehran, iran

چکیده

background: the rapid increase of hiv-1 strains resistant to current antiretroviral drugs is a challenge for successful aids therapy. this necessitates the development of novel drugs, and to this end, availability of screening systems for in vitro drug discovery is a priority. herein, we report the modification of a previously developed system for increased sensitivity, ease of use, and cost-efficiency, based on the application of the egfp marker. methods: a pcr-amplified gfp gene (gfp) was cloned into pmznl4-3, the plasmid already designed to produce single-cycle replicable virions, in frame with the reverse-transcriptase gene to construct the pmznl4-3/gfp plasmid. gfp-mznl4-3 pseudo-typed virions, as the first progeny viruses, were recovered from the culture supernatant of hek293t cells co-transfected with pmznl4-3/gfp and the helper plasmids pspax2 and pmd2g, which respectively encode hiv-1 gag-pol and vesicular stomatitis virus glycoprotein. single-cycle replication and virion production were assessed by syncytia formation, p24 antigen assays, and electron and fluorescence microscopy. results: the incorporation of egfp into the viral particles allowed their quantification by fluorometry, flow-cytometry, and fluorescence microscopy; however, this modification did not affect the single-round infectivity or production rate of the gfp fluorescence-emitting virions. conclusions: our results certify the development of a rapid, inexpensive, and safe gfp-reporting single-cycle replicable system for anti-hiv drug discovery. further experiments are needed to measure the validity and robustness of the assay.

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Toward the Development of a Single-Round Infection Assay Based on EGFP Reporting for Anti-HIV-1 Drug Discovery

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عنوان ژورنال:
reports of biochemistry and molecular biology

جلد ۴، شماره ۱، صفحات ۱-۹

کلمات کلیدی
[ ' d r u g d i s c o v e r y ' , ' e g f p ' , ' f l u o r o m e t r y ' , ' h i v ' , 1 , ' s i n g l e ' , ' r o u n d i n f e c t i o n ' ]

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