2017
DOI: 10.1186/s13578-016-0131-5
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A fission yeast cell-based system for multidrug resistant HIV-1 proteases

Abstract: BackgroundHIV-1 protease (PR) is an essential enzyme for viral production. Thus, PR inhibitors (PIs) are the most effective class of anti-HIV drugs. However, the main challenge to the successful use of PI drugs in patient treatment is the emergence of multidrug resistant PRs (mdrPRs). This study aimed to develop a fission yeast cell-based system for rapid testing of new PIs that combat mdrPRs.ResultsThree mdrPRs were isolated from HIV-infected patients that carried seven (M7PR), ten (M10PR) and eleven (M11PR) … Show more

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Cited by 11 publications
(44 citation statements)
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“…Expression of exogenous viral proteins also induce cell death and apoptosis in yeasts 64 174 . Viral proteins that induced yeast cell death and apoptosis include, but are not limited to, pro-apoptotic proteins such as adenovirus E4orf4 protein 175 , HIV-1 Vpr 67 176 , HIV-1 protease (PR) 177 178 179 180 , and ZIKV proteins 36 . Anti-apoptotic viral proteins include baculovirus p35 174 and DPV022 protein of the Deerpox virus 181 .…”
Section: Yeast For Understanding Virus-host Interactionsmentioning
confidence: 99%
“…Expression of exogenous viral proteins also induce cell death and apoptosis in yeasts 64 174 . Viral proteins that induced yeast cell death and apoptosis include, but are not limited to, pro-apoptotic proteins such as adenovirus E4orf4 protein 175 , HIV-1 Vpr 67 176 , HIV-1 protease (PR) 177 178 179 180 , and ZIKV proteins 36 . Anti-apoptotic viral proteins include baculovirus p35 174 and DPV022 protein of the Deerpox virus 181 .…”
Section: Yeast For Understanding Virus-host Interactionsmentioning
confidence: 99%
“…Finally, we would like to point out that the methodology described in this study could be exploited as an assay system for inhibitors against any human proteins of interest. Provided that overproduction of those human proteins display some defective phenotypes including lethality, which is often the case (Benko et al, 2017;Matsuyama et al, 2006;Nkeze et al, 2015), small molecule libraries, natural products or extracts from any organism could be used to identify potential inhibitors (Figure 4). In fact, we have recently obtained small molecules derived from plants that specifically rescue lethality caused by HSET overproduction with very little cytotoxicity on their own (M.Y., T.T., and K.K., unpublished results).…”
Section: Discussionmentioning
confidence: 99%
“…those promoting lifespan extension (Sarnoski et al, 2017). Fission yeast has been used for several screenings, such as purification of specific compounds produced by Actinomycetes (Lewis et al, 2017) and a functional assay for Indinavir, an inhibitor against Human Immunodeficiency Virus Type-1 (Benko et al, 2016;Benko et al, 2017;Yang et al, 2012). Having seen toxicity derived from overproduced HSET in fission yeast cells (see Figure 1A), we exploited this lethal phenotype for the biological evaluation of known HSET inhibitors described earlier (AZ82, CW069 and SR31527) (Cosenza and Kramer, 2016;Xiao and Yang, 2016;Zhang et al, 2016).…”
Section: An Assay System For Evaluation Of Human Kinesin-14 Inhibitormentioning
confidence: 99%
“…Provided that overproduction of those human proteins display some defective phenotypes including lethality, which is often the case (Benko et al, 2017;Matsuyama et al, 2006;Nkeze et al, 2015), small molecule libraries, natural products or extracts from any organism could be used to identify potential inhibitors (Fig. 5A).…”
Section: Discussionmentioning
confidence: 99%
“…those promoting lifespan extension (Sarnoski et al, 2017). Fission yeast has been used for several screenings, such as purification of specific compounds produced by Actinomycetes (Lewis et al, 2017) and a functional assay for Indinavir, an inhibitor against Human Immunodeficiency Virus Type-1 (Benko et al, 2016;Benko et al, 2017;Yang et al, 2012). Having seen toxicity derived from overproduced HSET in fission yeast cells (see Fig.…”
Section: An Assay System For Evaluation Of Human Kinesin-14 Inhibitormentioning
confidence: 99%