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Amphotericin B Inhibits Enterovirus 71 Replication by Impeding Viral Entry

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ABSTRACT

Enterovirus 71 (EV71) infection causes hand-foot-and-mouth disease that leads to cardiopulmonary complications and death in young children. There is thus an urgent need to find new treatments to control EV71 infection. In this study, we report potent inhibition of EV71 by a polyene antibiotic Amphotericin B. Amphotericin B profoundly diminished the expression of EV71 RNA and viral proteins in the RD cells and the HEK293 cells. As a result, EV71 production was inhibited by Amphotericin B with an EC50 (50% effective concentration) of 1.75 μM in RD cells and 0.32 μM in 293 cells. In addition to EV71, EV68 was also strongly inhibited by Amphotericin B. Results of mechanistic studies revealed that Amphotericin B targeted the early stage of EV71 infection through impairing the attachment and internalization of EV71 by host cells. As an effective anti-fungi drug, Amphotericin B thus holds the promise of formulating a novel therapeutic to treat EV71 infection.

No MeSH data available.


Amphotericin B inhibits EV68 infection.RD cells were pretreated with Amphotericin B at indicated concentrations for 2 h and then inoculated with EV68 at an MOI of 0.02. After 20 h, cells were harvested for western blotting and RNA extraction. (a) Levels of EV68 3C protein as determined by Western blotting at 20 hpi. Full-length blots are presented in Supplementary Fig. 5. (b) Levels of EV68 RNA were determined by qRT-PCR. Levels of viral RNA were normalized to GAPDH mRNA. Data represented percentage of Amphotericin B treatment to DMSO treatment. Results shown are the average of three independent experiments. Error bars represent SD (**P < 0.01, t test).
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f6: Amphotericin B inhibits EV68 infection.RD cells were pretreated with Amphotericin B at indicated concentrations for 2 h and then inoculated with EV68 at an MOI of 0.02. After 20 h, cells were harvested for western blotting and RNA extraction. (a) Levels of EV68 3C protein as determined by Western blotting at 20 hpi. Full-length blots are presented in Supplementary Fig. 5. (b) Levels of EV68 RNA were determined by qRT-PCR. Levels of viral RNA were normalized to GAPDH mRNA. Data represented percentage of Amphotericin B treatment to DMSO treatment. Results shown are the average of three independent experiments. Error bars represent SD (**P < 0.01, t test).

Mentions: Over 1000 cases of severe respiratory diseases in pediatric patients were reported to associate with enterovirus 68 (EV68) infection in the fall of 20144647. We have therefore measured the effect of Amphotericin B on EV68 infection. RD cells were infected with EV68 in the absence or presence of Amphotericin B, and viral 3 C protein expression was examined by Western blotting. The results showed that expression of EV68 3 C protein was significantly diminished by Amphotericin B in a dose dependent manner (Fig. 6a). This inhibition was corroborated by the results of RT-PCR showing similar trend of decrease of viral RNA under the treatment of Amphotericin B (Fig. 6b). Together, these data demonstrate that Amphotericin B also inhibits EV68 infection.


Amphotericin B Inhibits Enterovirus 71 Replication by Impeding Viral Entry
Amphotericin B inhibits EV68 infection.RD cells were pretreated with Amphotericin B at indicated concentrations for 2 h and then inoculated with EV68 at an MOI of 0.02. After 20 h, cells were harvested for western blotting and RNA extraction. (a) Levels of EV68 3C protein as determined by Western blotting at 20 hpi. Full-length blots are presented in Supplementary Fig. 5. (b) Levels of EV68 RNA were determined by qRT-PCR. Levels of viral RNA were normalized to GAPDH mRNA. Data represented percentage of Amphotericin B treatment to DMSO treatment. Results shown are the average of three independent experiments. Error bars represent SD (**P < 0.01, t test).
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Related In: Results  -  Collection

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f6: Amphotericin B inhibits EV68 infection.RD cells were pretreated with Amphotericin B at indicated concentrations for 2 h and then inoculated with EV68 at an MOI of 0.02. After 20 h, cells were harvested for western blotting and RNA extraction. (a) Levels of EV68 3C protein as determined by Western blotting at 20 hpi. Full-length blots are presented in Supplementary Fig. 5. (b) Levels of EV68 RNA were determined by qRT-PCR. Levels of viral RNA were normalized to GAPDH mRNA. Data represented percentage of Amphotericin B treatment to DMSO treatment. Results shown are the average of three independent experiments. Error bars represent SD (**P < 0.01, t test).
Mentions: Over 1000 cases of severe respiratory diseases in pediatric patients were reported to associate with enterovirus 68 (EV68) infection in the fall of 20144647. We have therefore measured the effect of Amphotericin B on EV68 infection. RD cells were infected with EV68 in the absence or presence of Amphotericin B, and viral 3 C protein expression was examined by Western blotting. The results showed that expression of EV68 3 C protein was significantly diminished by Amphotericin B in a dose dependent manner (Fig. 6a). This inhibition was corroborated by the results of RT-PCR showing similar trend of decrease of viral RNA under the treatment of Amphotericin B (Fig. 6b). Together, these data demonstrate that Amphotericin B also inhibits EV68 infection.

View Article: PubMed Central - PubMed

ABSTRACT

Enterovirus 71 (EV71) infection causes hand-foot-and-mouth disease that leads to cardiopulmonary complications and death in young children. There is thus an urgent need to find new treatments to control EV71 infection. In this study, we report potent inhibition of EV71 by a polyene antibiotic Amphotericin B. Amphotericin B profoundly diminished the expression of EV71 RNA and viral proteins in the RD cells and the HEK293 cells. As a result, EV71 production was inhibited by Amphotericin B with an EC50 (50% effective concentration) of 1.75&thinsp;&mu;M in RD cells and 0.32&thinsp;&mu;M in 293 cells. In addition to EV71, EV68 was also strongly inhibited by Amphotericin B. Results of mechanistic studies revealed that Amphotericin B targeted the early stage of EV71 infection through impairing the attachment and internalization of EV71 by host cells. As an effective anti-fungi drug, Amphotericin B thus holds the promise of formulating a novel therapeutic to treat EV71 infection.

No MeSH data available.