Abstract:
BACKGROUND:The high rate of HIV-1 mutation and increasing resistance to currently available antiretroviral (ART) therapies highlight the need for new antiviral agents. Products derived from natural sources have been shown to inhibit HIV-1 replication during various stages of the virus life cycle, and therefore represent a potential source of novel therapeutic agents. To expand our arsenal of therapeutics against HIV-1 infection, we investigated aqueous extract from Sargassum fusiforme (S. fusiforme) for ability to inhibit HIV-1 infection in the periphery, in T cells and human macrophages, and for ability to inhibit in the central nervous system (CNS), in microglia and astrocytes. RESULTS:S. fusiforme extract blocked HIV-1 infection and replication by over 90% in T cells, human macrophages and microglia, and it also inhibited pseudotyped HIV-1 (VSV/NL4-3) infection in human astrocytes by over 70%. Inhibition was mediated against both CXCR4 (X4) and CCR5 (R5)-tropic HIV-1, was dose dependant and long lasting, did not inhibit cell growth or viability, was not toxic to cells, and was comparable to inhibition by the nucleoside analogue 2', 3'-didoxycytidine (ddC). S. fusiforme treatment blocked direct cell-to-cell infection spread. To investigate at which point of the virus life cycle this inhibition occurs, we infected T cells and CD4-negative primary human astrocytes with HIV-1 pseudotyped with envelope glycoprotein of vesicular stomatitis virus (VSV), which bypasses the HIV receptor requirements. Infection by pseudotyped HIV-1 (VSV/NL4-3) was also inhibited in a dose dependant manner, although up to 57% less, as compared to inhibition of native NL4-3, indicating post-entry interferences. CONCLUSION:This is the first report demonstrating S. fusiforme to be a potent inhibitor of highly productive HIV-1 infection and replication in T cells, in primary human macrophages, microglia, and astrocytes. Results with VSV/NL4-3 infection, suggest inhibition of both entry and post-entry events of the virus life cycle. Absence of cytotoxicity and high viability of treated cells also suggest that S. fusiforme is a potential source of novel naturally occurring antiretroviral compounds that inhibit HIV-1 infection and replication at more than one site of the virus life cycle.
journal_name
AIDS Res Therjournal_title
AIDS research and therapyauthors
Paskaleva EE,Lin X,Li W,Cotter R,Klein MT,Roberge E,Yu EK,Clark B,Veille JC,Liu Y,Lee DY,Canki Mdoi
10.1186/1742-6405-3-15subject
Has Abstractpub_date
2006-05-25 00:00:00pages
15issn
1742-6405pii
1742-6405-3-15journal_volume
3pub_type
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journal_title:AIDS research and therapy
pub_type: 杂志文章
doi:10.1186/1742-6405-4-15
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journal_title:AIDS research and therapy
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journal_title:AIDS research and therapy
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pub_type: 杂志文章
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pub_type: 杂志文章,评审
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pub_type: 杂志文章,评审
doi:10.1186/s12981-017-0162-y
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journal_title:AIDS research and therapy
pub_type: 杂志文章
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journal_title:AIDS research and therapy
pub_type: 杂志文章
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journal_title:AIDS research and therapy
pub_type: 杂志文章
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journal_title:AIDS research and therapy
pub_type: 杂志文章
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