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Updated: Jun 6, 2026

siRNA Electroporation to Modulate Autophagy in Herpes Simplex Virus Type 1-Infected Monocyte-Derived Dendritic Cells
Published on: October 28, 2019
Foot-and-mouth disease virus utilizes an autophagic pathway during viral replication
Vivian O'Donnell1, Juan M Pacheco, Michael LaRocco
1Foreign Animal Disease Research Unit, United States Department of Agriculture, Agricultural Research Service, Plum Island Animal Disease Center, Greenport, NY 11944, USA. vivian.odonnell@ars.usda.gov
Abstract:
Foot-and-mouth disease virus (FMDV) is the type species of the Aphthovirus genus within the Picornaviridae family. Infection of cells with positive-strand RNA viruses results in a rearrangement of intracellular membranes into viral replication complexes. The origin of these membranes remains unknown; however induction of the cellular process of autophagy is beneficial for the replication of poliovirus, suggesting that it might be advantageous for other picornaviruses. By using confocal microscopy we showed in FMDV-infected cells co-localization of non-structural viral proteins 2B, 2C and 3A with LC3 (an autophagosome marker) and viral structural protein VP1 with Atg5 (autophagy-related protein), and LC3 with LAMP-1. Importantly, treatment of FMDV-infected cell with autophagy inducer rapamycin, increased viral yield, and inhibition of autophagosomal pathway by 3-methyladenine or small-interfering RNAs, decreased viral replication. Altogether, these studies strongly suggest that autophagy may play an important role during the replication of FMDV.
Insights
Autophagy, a cellular process, aids Foot-and-mouth disease virus (FMDV) replication. Enhancing autophagy boosts FMDV yield, while inhibiting it reduces viral replication, highlighting autophagy's crucial role in the FMDV life cycle.
Area of Science:
- Virology
- Cell Biology
- Molecular Biology
Background:
- Foot-and-mouth disease virus (FMDV), an Aphthovirus, replicates within host cells, inducing membrane rearrangements for viral replication complexes.
- The origin of these induced membranes is unclear, but autophagy benefits poliovirus replication, suggesting a similar role for other picornaviruses.
Purpose of the Study:
- To investigate the role of autophagy in the replication cycle of Foot-and-mouth disease virus (FMDV).
- To determine if modulating autophagy affects FMDV replication efficiency.
Main Methods:
- Confocal microscopy was employed to visualize the co-localization of viral proteins (2B, 2C, 3A, VP1) with autophagy markers (LC3, Atg5) and LAMP-1 in FMDV-infected cells.
- The impact of autophagy modulation (using rapamycin to induce, and 3-methyladenine or siRNAs to inhibit) on viral yield and replication was assessed.
Main Results:
- Co-localization of FMDV non-structural proteins (2B, 2C, 3A) with LC3 and structural protein VP1 with Atg5 was observed, indicating interaction with the autophagic pathway.
- Treatment with the autophagy inducer rapamycin significantly increased FMDV yield.
- Inhibition of the autophagosomal pathway using 3-methyladenine or small-interfering RNAs markedly decreased FMDV replication.
Conclusions:
- Autophagy plays a significant role in the replication of Foot-and-mouth disease virus (FMDV).
- Modulation of the autophagic pathway directly impacts FMDV replication efficiency, suggesting it as a potential target for antiviral strategies.
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