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Epigallocatechin-3-gallate rapidly remodels PAP85-120, SEM1(45-107), and SEM2(49-107) seminal amyloid fibrils.

Castellano LM, Hammond RM, Holmes VM, Weissman D, Shorter J - Biol Open (2015)

Bottom Line: Here, we confirm that the green tea polyphenol, epigallocatechin-3-gallate (EGCG), slowly remodels fibrils formed by PAP248-286 termed SEVI (semen derived enhancer of viral infection) and also exerts a direct anti-viral effect.We elucidate for the first time that EGCG remodels PAP85-120, SEM1(45-107), and SEM2(49-107) fibrils more rapidly than SEVI fibrils.The combined anti-amyloid and anti-viral properties of EGCG could have utility in preventing HIV transmission.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA Pharmacology Graduate Group, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.

No MeSH data available.


Related in: MedlinePlus

EGCG inhibits HIV infectivity in cell culture. TZM-bl cells were infected with three HIV-1 strains (BL2, BaL, and 89.6) in the presence of the indicated concentrations of EGCG (final concentration in cell culture). Infectivity was monitored by measuring luciferase activity in the cell cultures. Values represent means±s.e.m. (n=3).
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BIO010215F5: EGCG inhibits HIV infectivity in cell culture. TZM-bl cells were infected with three HIV-1 strains (BL2, BaL, and 89.6) in the presence of the indicated concentrations of EGCG (final concentration in cell culture). Infectivity was monitored by measuring luciferase activity in the cell cultures. Values represent means±s.e.m. (n=3).

Mentions: EGCG is the first agent that has been found to disrupt the amyloid architecture of all four classes of seminal amyloids that have been identified (SEVI, PAP85-120, SEM1, and SEM2). Previous work reported that EGCG counteracts the viral infection enhancing activity of SEVI (Hauber et al., 2009). Thus, we next wanted to determine whether the products of PAP85-120, SEM1(45-107) and SEM2(49-107) fibril remodeling by EGCG also had a reduced capacity to boost HIV infectivity. Unfortunately, however, our analysis was confounded, since EGCG on its own exhibited a marked anti-viral effect against three different HIV strains (Fig. 5). At a concentration of only 0.25 µM EGCG, viral infectivity was reduced to ∼61%, ∼35%, and ∼11% of the control condition against the HIV-1 viral strains BL2, BaL, and 89.6, respectively (Fig. 5). When the EGCG concentration was increased to 1.25 µM or higher, the infectivity of all three strains was essentially abolished. In accord with previous studies (Bieschke et al., 2010; Ehrnhoefer et al., 2008; Hauber et al., 2009), none of the EGCG concentrations tested were toxic to cells as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay (data not shown). The direct anti-HIV effect of EGCG has been previously described and is proposed to occur through a variety of mechanisms (Fassina et al., 2002; Kawai et al., 2003; Steinmann et al., 2013; Yamaguchi et al., 2002). This direct anti-viral property in combination with the ability of EGCG to disaggregate SEVI, PAP85-120, SEM1(45-107) and SEM2(49-107) seminal amyloids highlight the potential for the use of EGCG in a preventative HIV microbicide with dual mechanisms of action.Fig. 5.


Epigallocatechin-3-gallate rapidly remodels PAP85-120, SEM1(45-107), and SEM2(49-107) seminal amyloid fibrils.

Castellano LM, Hammond RM, Holmes VM, Weissman D, Shorter J - Biol Open (2015)

EGCG inhibits HIV infectivity in cell culture. TZM-bl cells were infected with three HIV-1 strains (BL2, BaL, and 89.6) in the presence of the indicated concentrations of EGCG (final concentration in cell culture). Infectivity was monitored by measuring luciferase activity in the cell cultures. Values represent means±s.e.m. (n=3).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4582112&req=5

BIO010215F5: EGCG inhibits HIV infectivity in cell culture. TZM-bl cells were infected with three HIV-1 strains (BL2, BaL, and 89.6) in the presence of the indicated concentrations of EGCG (final concentration in cell culture). Infectivity was monitored by measuring luciferase activity in the cell cultures. Values represent means±s.e.m. (n=3).
Mentions: EGCG is the first agent that has been found to disrupt the amyloid architecture of all four classes of seminal amyloids that have been identified (SEVI, PAP85-120, SEM1, and SEM2). Previous work reported that EGCG counteracts the viral infection enhancing activity of SEVI (Hauber et al., 2009). Thus, we next wanted to determine whether the products of PAP85-120, SEM1(45-107) and SEM2(49-107) fibril remodeling by EGCG also had a reduced capacity to boost HIV infectivity. Unfortunately, however, our analysis was confounded, since EGCG on its own exhibited a marked anti-viral effect against three different HIV strains (Fig. 5). At a concentration of only 0.25 µM EGCG, viral infectivity was reduced to ∼61%, ∼35%, and ∼11% of the control condition against the HIV-1 viral strains BL2, BaL, and 89.6, respectively (Fig. 5). When the EGCG concentration was increased to 1.25 µM or higher, the infectivity of all three strains was essentially abolished. In accord with previous studies (Bieschke et al., 2010; Ehrnhoefer et al., 2008; Hauber et al., 2009), none of the EGCG concentrations tested were toxic to cells as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay (data not shown). The direct anti-HIV effect of EGCG has been previously described and is proposed to occur through a variety of mechanisms (Fassina et al., 2002; Kawai et al., 2003; Steinmann et al., 2013; Yamaguchi et al., 2002). This direct anti-viral property in combination with the ability of EGCG to disaggregate SEVI, PAP85-120, SEM1(45-107) and SEM2(49-107) seminal amyloids highlight the potential for the use of EGCG in a preventative HIV microbicide with dual mechanisms of action.Fig. 5.

Bottom Line: Here, we confirm that the green tea polyphenol, epigallocatechin-3-gallate (EGCG), slowly remodels fibrils formed by PAP248-286 termed SEVI (semen derived enhancer of viral infection) and also exerts a direct anti-viral effect.We elucidate for the first time that EGCG remodels PAP85-120, SEM1(45-107), and SEM2(49-107) fibrils more rapidly than SEVI fibrils.The combined anti-amyloid and anti-viral properties of EGCG could have utility in preventing HIV transmission.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA Pharmacology Graduate Group, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.

No MeSH data available.


Related in: MedlinePlus