title: Inhibition of highly productive HIV-1 infection in T cells, primary human macrophages, microglia, and astrocytes by Sargassum fusiforme.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center for Immunology and Microbial Disease, Albany Medical College, Albany, NY, USA. paskale@mail.amc.edu
authors.forename: Elena E
authors.initials: EE
authors.lastname: Paskaleva
authors.forename: Xudong
authors.initials: X
authors.lastname: Lin
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.forename: Robin
authors.initials: R
authors.lastname: Cotter
authors.forename: Michael T
authors.initials: MT
authors.lastname: Klein
authors.forename: Emily
authors.initials: E
authors.lastname: Roberge
authors.forename: Er K
authors.initials: EK
authors.lastname: Yu
authors.forename: Bruce
authors.initials: B
authors.lastname: Clark
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Veille
authors.forename: Yanze
authors.initials: Y
authors.lastname: Liu
authors.forename: David Y-W
authors.initials: DY
authors.lastname: Lee
authors.forename: Mario
authors.initials: M
authors.lastname: Canki