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Updated: Aug 11, 2026
Modeling The Lifecycle Of Ebola Virus Under Biosafety Level 2 Conditions With Virus-like Particles Containing Tetracistronic Minigenomes
Published on: September 27, 2014
VP35 knockdown inhibits Ebola virus amplification and protects against lethal infection in mice
Sven Enterlein1, Kelly L Warfield, Dana L Swenson
1Department of Virology, Philipps-University Marburg, Hans-Meerwein-Str. 3, 35043 Marburg, Germany.
Abstract:
Phosphorodiamidate morpholino oligomers (PMO) are a class of uncharged single-stranded DNA analogs modified such that each subunit includes a phosphorodiamidate linkage and morpholine ring. PMO antisense agents have been reported to effectively interfere with the replication of several positive-strand RNA viruses in cell culture. The filoviruses, Marburg virus and Ebola virus (EBOV), are negative-strand RNA viruses that cause up to 90% lethality in human outbreaks. There is currently no commercially available vaccine or efficacious therapeutic for any filovirus. In this study, PMO conjugated to arginine-rich cell-penetrating peptide (P-PMO) and nonconjugated PMO were assayed for the ability to inhibit EBOV infection in cell culture and in a mouse model of lethal EBOV infection. A 22-mer P-PMO designed to base pair with the translation start site region of EBOV VP35 positive-sense RNA generated sequence-specific and time- and dose-dependent inhibition of EBOV amplification in cell culture. The same oligomer provided complete protection to mice when administered before or after an otherwise lethal infection of EBOV. A corresponding nonconjugated PMO, as well as nonconjugated truncated versions of 16 and 19 base residues, provided length-dependent protection to mice when administered prophylactically. Together, these data suggest that antisense PMO and P-PMO have the potential to control EBOV infection and are promising therapeutic candidates.
Insights
Phosphorodiamidate morpholino oligomers (PMO) show promise in combating Ebola virus (EBOV). These compounds, including peptide-conjugated PMO (P-PMO), effectively inhibited EBOV in cell cultures and protected mice from lethal infection.
Area of Science:
- Biochemistry
- Virology
- Antimicrobial Agents
Background:
- Phosphorodiamidate morpholino oligomers (PMO) are uncharged DNA analogs.
- PMOs can interfere with positive-strand RNA virus replication.
- Ebola virus (EBOV) is a lethal negative-strand RNA virus with no current vaccine or therapy.
Purpose of the Study:
- To evaluate the efficacy of PMO and peptide-conjugated PMO (P-PMO) against EBOV infection.
- To assess the therapeutic potential of these agents in cell culture and a mouse model.
Main Methods:
- A 22-mer P-PMO targeting EBOV VP35 RNA was synthesized.
- Inhibition of EBOV amplification was measured in cell culture.
- Protection against lethal EBOV infection was assessed in mice using PMO and P-PMO.
Main Results:
- P-PMO demonstrated sequence-specific, time-, and dose-dependent inhibition of EBOV in cell culture.
- P-PMO provided complete protection in mice against lethal EBOV infection, even when administered post-infection.
- Nonconjugated PMOs also offered length-dependent protection in a prophylactic setting.
Conclusions:
- Antisense PMO and P-PMO are effective against EBOV.
- These agents show significant potential as therapeutic candidates for EBOV infection.
