Inhibition of highly productive HIV-1 infection in T cells, primary human macrophages, microglia, and astrocytes by Sargassum fusiforme.

Full 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.

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Author information

Author/s: Paskaleva, Elena E (EE); Lin, Xudong (X); Li, Wen (W); Cotter, Robin (R); Klein, Michael T (MT); Roberge, Emily (E); Yu, Er K (EK); Clark, Bruce (B); Veille, Jean-Claude (JC); Liu, Yanze (Y); Lee, David Y-W (DY); Canki, Mario (M);

Affiliation: Center for Immunology and Microbial Disease, Albany Medical College, Albany, NY, USA. paskale(-atsign-)mail.amc.edu

Journal and publication information

Publication Type: Journal Article

Journal: AIDS research and therapy (AIDS Res Ther), published in England. (Language: eng)

Reference: 2006-; vol 3 (issue ) : pp 15

Dates: Created 2006/06/22; Completed 2007/07/27; Revised 2008/11/20;

PMID: 16725040, status: PubMed-not-MEDLINE (last retrieval date: 12/26/2008)

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