2013 Fiscal Year Final Research Report
Impact of HIV infection pathway on the potency of antiviral agents
| Project/Area Number |
24791021
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Infectious disease medicine
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| Research Institution | Kyoto University |
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Principal Investigator |
SHIMURA Kazuya 京都大学, ウイルス研究所, 助教 (90613836)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Keywords | HIV / 抗ウイルス薬 |
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| Research Abstract |
HIV infects target cells by two pathways, cell-free infection and cell-to-cell transmission. In cell-free infection, HIV virions present in the intercellular space infect target cells, while in cell-to-cell transmission, HIV is transmitted from infected to uninfected cells through cellular gap. To analyze the effect of infection pathways on drug susceptibility, we established an assay system, in which HIV-1 carrying a fluorescent protein gene, and a cell-labeling dye were utilized for precise quantification of HIV-1-infected cells under cell-free infection and cell-to-cell transmission separately. Using this system, inhibitory activity of anti-HIV drugs targeting several replication steps was evaluated. Overall, weak anti-HIV activity of tested drugs under the cell-to-cell pathway compared to the cell-free pathway with several-fold ranges, was observed. Taken together, infection pathway of HIV affects the activity of anti-HIV drugs.
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[Journal Article] Structure-activity relationship study of phenylpyrazole derivatives as a novel class of anti-HIV agents2013
Author(s)
Mizuhara T, Kato T, Hirai A, Kurihara H, Shimada Y, Taniguchi M, Maeta H, Togami H, Shimura K, Matsuoka M, Okazaki S, Takeuchi T, Ohno H, Oishi S, Fujii N
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Journal Title
Bioorg Med Chem Lett
Volume: 23(16)
Pages: 4557-61
DOI
Peer Reviewed
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[Journal Article] HIV-1 resistance mechanism to an electrostatically constrained peptide fusion inhibitor that is active against T-20-resistant strains2013
Author(s)
Shimane K, Kawaji K, Miyamoto F, Oishi S, Watanabe K, Sakagami Y, Fujii N, Shimura K, Matsuoka M, Kaku M, Sarafianos SG, Kodama EN
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Journal Title
Antimicrob Agents Chemother
Volume: 57(8)
Pages: 4035-8
DOI
Peer Reviewed
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[Journal Article] Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design2013
Author(s)
Izumi K, Kawaji K, Miyamoto F, Shimane K, Shimura K, Sakagami Y, Hattori T, Watanabe K, Oishi S, Fujii N, Matsuoka M, Kaku M, Sarafianos SG, Kodama EN
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Journal Title
Int J Biochem Cell Biol
Volume: 45(4)
Pages: 908-15
DOI
Peer Reviewed
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[Journal Article] CXCR4 stimulates macropinocytosis : implications for cellular uptake of arginine-rich cell-penetrating peptides and HIV2012
Author(s)
Tanaka G, Nakase I, Fukuda Y, Masuda R, Oishi S, Shimura K, Kawaguchi Y, Takatani-Nakase T, Langel U, Gräslund A, Okawa K, Matsuoka M, Fujii N, Hatanaka Y, Futaki S
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Journal Title
Chem Biol
Volume: 19(11)
Pages: 1437-46
DOI
Peer Reviewed
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