Inhibition of Highly Productive HIV-1 Infection in T Cells, Primary Human Macrophages, Microglia and Astrocytes by Sargassum Fusiforme [chapter]

Elena Paskaleva, Xudong Lin, Wen Li, Robin Cotter, Michael Klein, Emily Roberge, Er Yu, Bruce Clark, Jean-Claude Veille, Yanze Liu, David Lee, Mario Canki
2014 Recent Advances in Plant-Based, Traditional, and Natural Medicines  
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
more » ... ility 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. number, and (D) % viable cells from total. PBMC's experiments are representative of 3 separate experiments, with SEM less than 5% (not shown). J J J J J ddC H S. fusiforme 2mg/ml F S. fusiforme 4mg/ml J J J J A) 1G5 Cell Growth B) 1G5 Viability J J J D) PBMC Viability C) PBMC Cell Growth J J J J
doi:10.1201/b16611-14 fatcat:svfdt43fajgpnklqusb2yj3gki