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Investigation of Stilbenoids as Potential Therapeutic Agents for Rotavirus Gastroenteritis.

Ball JM, Medina-Bolivar F, Defrates K, Hambleton E, Hurlburt ME, Fang L, Yang T, Nopo-Olazabal L, Atwill RL, Ghai P, Parr RD - Adv Virol (2015)

Bottom Line: Cell viability counts showed no cytotoxic effects on HT29.f8 cells.Two stilbenoids, trans-arachidin-1 and trans-arachidin-3, show a significant decrease in RV infectivity titers.Western blot analyses performed on the infected cell lysates complemented the infectivity titrations and indicated a significant decrease in viral replication.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathobiology, Texas A&M University, College Station, TX 77843, USA.

ABSTRACT
Rotavirus (RV) infections cause severe diarrhea in infants and young children worldwide. Vaccines are available but cost prohibitive for many countries and only reduce severe symptoms. Vaccinated infants continue to shed infectious particles, and studies show decreased efficacy of the RV vaccines in tropical and subtropical countries where they are needed most. Continuing surveillance for new RV strains, assessment of vaccine efficacy, and development of cost effective antiviral drugs remain an important aspect of RV studies. This study was to determine the efficacy of antioxidant and anti-inflammatory stilbenoids to inhibit RV replication. Peanut (A. hypogaea) hairy root cultures were induced to produce stilbenoids, which were purified by high performance countercurrent chromatography (HPCCC) and analyzed by HPLC. HT29.f8 cells were infected with RV in the presence stilbenoids. Cell viability counts showed no cytotoxic effects on HT29.f8 cells. Viral infectivity titers were calculated and comparatively assessed to determine the effects of stilbenoid treatments. Two stilbenoids, trans-arachidin-1 and trans-arachidin-3, show a significant decrease in RV infectivity titers. Western blot analyses performed on the infected cell lysates complemented the infectivity titrations and indicated a significant decrease in viral replication. These studies show the therapeutic potential of the stilbenoids against RV replication.

No MeSH data available.


Related in: MedlinePlus

Quantification of progeny RV via focus forming units/mL (FFU/mL) at 24 hours postinfection. HT29.8 cells were infected with RV, with RV containing 0.02% DMSO, or 10 μM/20 μM of (a) resveratrol (t-Res). (b) Piceatannol (t-Pa). (c) Arachidin-1 (t-A1) ∗p = 0.02 and ∗∗p = 0.001 and (d) arachidin-3 (t-A3) ∗p = 0.04, ∗∗p = 0.04, and ∗∗∗p = 0.02.
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fig4: Quantification of progeny RV via focus forming units/mL (FFU/mL) at 24 hours postinfection. HT29.8 cells were infected with RV, with RV containing 0.02% DMSO, or 10 μM/20 μM of (a) resveratrol (t-Res). (b) Piceatannol (t-Pa). (c) Arachidin-1 (t-A1) ∗p = 0.02 and ∗∗p = 0.001 and (d) arachidin-3 (t-A3) ∗p = 0.04, ∗∗p = 0.04, and ∗∗∗p = 0.02.

Mentions: Viral infectivity titers were determined using FFU assays from the supernatants of RV-infected HT29.f8 cells treated with stilbenoids (10 μM and 20 μM t-Res, t-PA, t-A1, or t-A3). Supernatants collected at 12 hpi were equivalent to the RV-infected control cells (data not shown). Similarly, at 24 hpi, the 20 μM concentrations of the nonprenylated stilbenoids, t-Res and t-PA both, demonstrated no change in the virus titer when compared to the RV-infected control (Figures 4(a) and 4(b)). However at 24 hpi, the 10 μM concentrations of t-A1 generated a tenfold decrease in virus infectivity titer when compared to the RV-infected control supernatants (p = 0.02), and the 20 μM concentrations of t-A1 generated a twenty-fivefold decrease in virus infectivity titer when compared to the RV-infected control supernatants (p = 0.001) (Figure 4(c)), However, there was a statistical difference between RV and RV with DMSO with an eightfold decrease in virus infectivity titers with RV and DMSO (p = 0.04) (Figure 4(d)). The 10 μM concentrations of t-A3 generated a ninefold decrease in virus titer when compared to the RV-infected control supernatants (p = 0.04), and the 20 μM concentrations of t-A3 generated a ninety-eightfold decrease in virus titer when compared to the RV-infected control supernatants (p = 0.02) (Figure 4(d)).


Investigation of Stilbenoids as Potential Therapeutic Agents for Rotavirus Gastroenteritis.

Ball JM, Medina-Bolivar F, Defrates K, Hambleton E, Hurlburt ME, Fang L, Yang T, Nopo-Olazabal L, Atwill RL, Ghai P, Parr RD - Adv Virol (2015)

Quantification of progeny RV via focus forming units/mL (FFU/mL) at 24 hours postinfection. HT29.8 cells were infected with RV, with RV containing 0.02% DMSO, or 10 μM/20 μM of (a) resveratrol (t-Res). (b) Piceatannol (t-Pa). (c) Arachidin-1 (t-A1) ∗p = 0.02 and ∗∗p = 0.001 and (d) arachidin-3 (t-A3) ∗p = 0.04, ∗∗p = 0.04, and ∗∗∗p = 0.02.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4563088&req=5

fig4: Quantification of progeny RV via focus forming units/mL (FFU/mL) at 24 hours postinfection. HT29.8 cells were infected with RV, with RV containing 0.02% DMSO, or 10 μM/20 μM of (a) resveratrol (t-Res). (b) Piceatannol (t-Pa). (c) Arachidin-1 (t-A1) ∗p = 0.02 and ∗∗p = 0.001 and (d) arachidin-3 (t-A3) ∗p = 0.04, ∗∗p = 0.04, and ∗∗∗p = 0.02.
Mentions: Viral infectivity titers were determined using FFU assays from the supernatants of RV-infected HT29.f8 cells treated with stilbenoids (10 μM and 20 μM t-Res, t-PA, t-A1, or t-A3). Supernatants collected at 12 hpi were equivalent to the RV-infected control cells (data not shown). Similarly, at 24 hpi, the 20 μM concentrations of the nonprenylated stilbenoids, t-Res and t-PA both, demonstrated no change in the virus titer when compared to the RV-infected control (Figures 4(a) and 4(b)). However at 24 hpi, the 10 μM concentrations of t-A1 generated a tenfold decrease in virus infectivity titer when compared to the RV-infected control supernatants (p = 0.02), and the 20 μM concentrations of t-A1 generated a twenty-fivefold decrease in virus infectivity titer when compared to the RV-infected control supernatants (p = 0.001) (Figure 4(c)), However, there was a statistical difference between RV and RV with DMSO with an eightfold decrease in virus infectivity titers with RV and DMSO (p = 0.04) (Figure 4(d)). The 10 μM concentrations of t-A3 generated a ninefold decrease in virus titer when compared to the RV-infected control supernatants (p = 0.04), and the 20 μM concentrations of t-A3 generated a ninety-eightfold decrease in virus titer when compared to the RV-infected control supernatants (p = 0.02) (Figure 4(d)).

Bottom Line: Cell viability counts showed no cytotoxic effects on HT29.f8 cells.Two stilbenoids, trans-arachidin-1 and trans-arachidin-3, show a significant decrease in RV infectivity titers.Western blot analyses performed on the infected cell lysates complemented the infectivity titrations and indicated a significant decrease in viral replication.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathobiology, Texas A&M University, College Station, TX 77843, USA.

ABSTRACT
Rotavirus (RV) infections cause severe diarrhea in infants and young children worldwide. Vaccines are available but cost prohibitive for many countries and only reduce severe symptoms. Vaccinated infants continue to shed infectious particles, and studies show decreased efficacy of the RV vaccines in tropical and subtropical countries where they are needed most. Continuing surveillance for new RV strains, assessment of vaccine efficacy, and development of cost effective antiviral drugs remain an important aspect of RV studies. This study was to determine the efficacy of antioxidant and anti-inflammatory stilbenoids to inhibit RV replication. Peanut (A. hypogaea) hairy root cultures were induced to produce stilbenoids, which were purified by high performance countercurrent chromatography (HPCCC) and analyzed by HPLC. HT29.f8 cells were infected with RV in the presence stilbenoids. Cell viability counts showed no cytotoxic effects on HT29.f8 cells. Viral infectivity titers were calculated and comparatively assessed to determine the effects of stilbenoid treatments. Two stilbenoids, trans-arachidin-1 and trans-arachidin-3, show a significant decrease in RV infectivity titers. Western blot analyses performed on the infected cell lysates complemented the infectivity titrations and indicated a significant decrease in viral replication. These studies show the therapeutic potential of the stilbenoids against RV replication.

No MeSH data available.


Related in: MedlinePlus