Defective Interfering Particles with Broad-Acting Antiviral Activity for Dengue, Zika, Yellow Fever, Respiratory Syncytial and SARS-CoV-2 Virus Infection

Min-Hsuan Lin; Dongsheng Li; Bing Tang; Li Li; Andreas Suhrbier; David Harrich

doi:10.1128/spectrum.03949-22

Microbiology Spectrum (Dec 2022)

Defective Interfering Particles with Broad-Acting Antiviral Activity for Dengue, Zika, Yellow Fever, Respiratory Syncytial and SARS-CoV-2 Virus Infection

Min-Hsuan Lin,
Dongsheng Li,
Bing Tang,
Li Li,
Andreas Suhrbier,
David Harrich

Affiliations

Min-Hsuan Lin: Program of Infection and Inflammation, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia
Dongsheng Li: Program of Infection and Inflammation, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia
Bing Tang: Program of Infection and Inflammation, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia
Li Li: Australian Institute for Bioengineering and Nanotechnology, the University of Queensland, St. Lucia, Queensland, Australia
Andreas Suhrbier: Program of Infection and Inflammation, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia
David Harrich: Program of Infection and Inflammation, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia

DOI: https://doi.org/10.1128/spectrum.03949-22
Journal volume & issue: Vol. 10, no. 6

Abstract

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ABSTRACT More than 100 arboviruses, almost all of which have an RNA genome, cause disease in humans. RNA viruses are causing unprecedented health system challenges worldwide, many with little or no specific therapies or vaccines available. Certain species of mosquito can carry dengue virus (DENV), Zika virus (ZIKV) and yellow fever virus (YFV), where co-infection of these viruses has occurred. Here, we found that purified synthetic defective interfering particles (DIPs) derived from DENV type 2 (DENV-2) strongly suppressed replication of the aforementioned viruses, respiratory syncytial virus (RSV) and also the novel emerging virus SARS-CoV-2 in human cells. DENV DIPs produced in bioreactors, purified by column chromatography, and concentrated are virus-like particles that are about half the diameter of a typical DENV particle, but with similar ratios of the viral structural proteins envelope and capsid. Overall, DIP-treated cells inhibited DENV, ZIKV, YFV, RSV, and SARS-CoV-2 by at least 98% by mechanisms which included interferon (IFN)-dependent cellular antiviral responses. IMPORTANCE DIPs are spontaneously derived virus mutants with deletions in genes that block viral replication. DIPs play important roles in modulation of viral disease, innate immune responses, virus persistence and virus evolution. Here, we investigated the antiviral activity of highly purified synthetic DIPs derived from DENV, which were produced in bioreactors. DENV DIPs purified by column chromatography strongly inhibited five different RNA viruses, including DENV, ZIKV, YFV, RSV, and SARS-CoV-2 in human cells. DENV DIPs inhibited virus replication via delivery of a small, noninfectious viral RNA that activated cellular innate immunity, resulting in robust type 1 interferon responses. The work here presents a pathway for DIP production which is adaptable to Good Manufacturing Practice, so that their preclinical testing should be suitable for evaluation in subjects.

Published in Microbiology Spectrum

ISSN: 2165-0497 (Online)
Publisher: American Society for Microbiology
Country of publisher: United States
LCC subjects: Science: Microbiology
Website: https://journals.asm.org/journal/spectrum

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