Defective Interfering Viral Particles in Acute Dengue Infections
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TLDR
In this article, short fragments of dengue virus (DENV) RNA containing only key regulatory elements at the 3' and 5' ends of the genome were recovered from the sera of patients infected with any of the four DENV serotypes.Abstract:
While much of the genetic variation in RNA viruses arises because of the error-prone nature of their RNA-dependent RNA polymerases, much larger changes may occur as a result of recombination. An extreme example of genetic change is found in defective interfering (DI) viral particles, where large sections of the genome of a parental virus have been deleted and the residual sub-genome fragment is replicated by complementation by co-infecting functional viruses. While most reports of DI particles have referred to studies in vitro, there is some evidence for the presence of DI particles in chronic viral infections in vivo. In this study, short fragments of dengue virus (DENV) RNA containing only key regulatory elements at the 3' and 5' ends of the genome were recovered from the sera of patients infected with any of the four DENV serotypes. Identical RNA fragments were detected in the supernatant from cultures of Aedes mosquito cells that were infected by the addition of sera from dengue patients, suggesting that the sub-genomic RNA might be transmitted between human and mosquito hosts in defective interfering (DI) viral particles. In vitro transcribed sub-genomic RNA corresponding to that detected in vivo could be packaged in virus like particles in the presence of wild type virus and transmitted for at least three passages in cell culture. DENV preparations enriched for these putative DI particles reduced the yield of wild type dengue virus following co-infections of C6-36 cells. This is the first report of DI particles in an acute arboviral infection in nature. The internal genomic deletions described here are the most extensive defects observed in DENV and may be part of a much broader disease attenuating process that is mediated by defective viruses.read more
Citations
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Journal ArticleDOI
Defective viral genomes are key drivers of the virus-host interaction.
Marco Vignuzzi,Carolina B. López +1 more
TL;DR: The universality and diversity of defective viral genomes during infections are highlighted and their predicted role in maintaining a fit virus population, their impact on human and animal health, and their potential to be harnessed as antiviral tools are discussed.
Journal ArticleDOI
Sequence analysis of in vivo defective interfering-like RNA of influenza A H1N1 pandemic virus.
K. Saira,Xudong Lin,Jay V. DePasse,Rebecca A. Halpin,Alan Twaddle,Timothy B. Stockwell,Brian Angus,Alessandro Cozzi-Lepri,Marina Delfino,Vivien G. Dugan,Dominic E. Dwyer,Matthew S. Freiberg,Andrzej Horban,Marcelo H. Losso,Ruth Lynfield,Deborah Wentworth,Edward C. Holmes,Edward C. Holmes,Richard J. Davey,David E. Wentworth,Elodie Ghedin +20 more
TL;DR: Several subgenomic viral RNAs from human nasopharyngeal specimens infected with the influenza A(H1N1)pdm09 virus are characterized using a sequencing approach, with the majority of the defective RNAs generated from the PB2 (segment 1) of the polymerase complex, followed by PB1 and PA.
Journal ArticleDOI
Defective Interfering Influenza Virus RNAs: Time To Reevaluate Their Clinical Potential as Broad-Spectrum Antivirals?
TL;DR: This review considers the early evidence of antiviral activity by DI viruses and outlines developments that have led to the production of a cloned DI RNA that is highly active in preclinical studies not only against different subtypes of influenza A virus but also against heterologous respiratory viruses.
Journal ArticleDOI
Defective Viral Genomes Arising In Vivo Provide Critical Danger Signals for the Triggering of Lung Antiviral Immunity
Karla Tapia,Won-Keun Kim,Yan Sun,Xiomara Mercado-López,Emily Dunay,Megan C. Wise,Michael Adu,Carolina B. López +7 more
TL;DR: It is shown that truncated forms of viral genomes that accumulate in infected cells potently trigger the sustained activation of the transcription factors IRF3 and NF-κB and the production type I IFNs through a mechanism independent of IFN signaling.
Journal ArticleDOI
Immunostimulatory Defective Viral Genomes from Respiratory Syncytial Virus Promote a Strong Innate Antiviral Response during Infection in Mice and Humans
Yan Sun,Deepika Jain,Cynthia J. Koziol-White,Emmanuelle Genoyer,Micah Gilbert,Karla Tapia,Reynold A. Panettieri,Richard L. Hodinka,Carolina B. López +8 more
TL;DR: It is demonstrated that immunostimulatory defective viral genomes that are naturally generated during RSV replication are strong inducers of the innate antiviral response to RSV in mice and humans and provide the first evidence for an important biological role for naturally occurring iDVGs during a paramyxovirus infection in humans.
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