Detection of Influenza Virus Induced Ultrastructural Changes and DNA Damage

Khanna, Madhu; Ray, Atish; Rawall, Shweta; Chandna, Sudhir; Kumar, Binod; Vijayan, Vini

doi:10.1007/s13337-010-0004-1

Cited by 7 publications

(6 citation statements)

References 26 publications

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“…By analyzing DNA repair foci (as indicated by γH2AX), results here show that there is a significant increase in DNA strand breaks in host cells after influenza infection, both in vitro and in vivo . Extending upon reports that DNA is damaged during influenza infection in vitro [55,56], the studies presented here show that DNA damage not only occurs early in viral infection, but persists until long after the virus has cleared. Additionally, analysis of specific cell types shows that both lung epithelial cells and immune cells suffer DNA damage during the regenerative phase of infection.…”

Section: Discussionsupporting

confidence: 68%

Influenza infection induces host DNA damage and dynamic DNA damage responses during tissue regeneration

Parrish

Chan

et al. 2015

Cell. Mol. Life Sci.

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Influenza viruses account for significant morbidity worldwide. Inflammatory responses, including excessive generation of reactive oxygen and nitrogen species (RONS), mediate lung injury in severe Influenza infections. However, the molecular basis of inflammation-induced lung damage is not fully understood. Here, we studied influenza H1N1 infected cells in vitro, as well as H1N1 infected mice, and we monitored molecular and cellular responses over the course of two weeks in vivo. We show that influenza induces DNA damage both when cells are directly exposed to virus in vitro (measured using the comet assay) and also when cells are exposed to virus in vivo (estimated via γH2AX foci). We show that DNA damage, as well as responses to DNA damage, persist in vivo until long after virus has been cleared, at times when there are inflammation associated RONS (measured by xanthine oxidase activity and oxidative products). The frequency of lung epithelial and immune cells with increased γH2AX foci is elevated in vivo, especially for dividing cells (Ki-67 positive) exposed to oxidative stress during tissue regeneration. Additionally, we observed a significant increase in apoptotic cells as well as increased levels of DSB repair proteins Ku70, Ku86 and Rad51 during the regenerative phase. In conclusion, results show that influenza induces DNA both in vitro and in vivo, and that DNA damage responses are activated, raising the possibility that DNA repair capacity may be a determining factor for tissue recovery and disease outcome.

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Section: Discussionsupporting

confidence: 68%

Influenza infection induces host DNA damage and dynamic DNA damage responses during tissue regeneration

Parrish

Chan

et al. 2015

Cell. Mol. Life Sci.

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“…Our observation of IAV-induced oxidative DNA damage is consistent with previous reports of DNA damage after IAV infection 22,40,41 . In addition to IAV, many other RNA viruses are known to cause significant DNA damage during infection 42 .…”

Section: Discussionsupporting

confidence: 93%

DNA mismatch repair is required for the host innate response and controls cellular fate after influenza virus infection

et al. 2019

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Despite the cytopathic nature of influenza A virus (IAV) replication, we recently reported that a subset of lung epithelial club cells is able to intrinsically clear virus and survive infection. However, the mechanisms that drive cell survival during a normally lytic infection remained unclear. Using a loss-of-function screening approach, we discovered that the DNA mismatch repair (MMR) pathway is essential for club cell survival of IAV infection. Repair of virallyinduced oxidative damage by the DNA MMR pathway not only allowed cell survival of infection but also facilitated host gene transcription, including the expression of antiviral and stress response genes. Enhanced viral suppression of the DNA MMR pathway prevented club cell survival and increased the severity of viral disease in vivo. Altogether, these results identify previously unappreciated roles for DNA MMR as a central modulator of cellular fate and a contributor to the innate antiviral response, which together, control influenza viral disease severity.

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“…However, only a few studies have focused on the impact of RNA viruses on DSB ( Chen et al., 2019 ; Hammack et al., 2019 ; Hristova et al., 2020 ; Ledur et al., 2020 ; Ryan et al., 2016 ). For Retroviridae and Orthomyxoviridae , controlling DSB levels is critical to delay the induction of apoptosis ( Hristova et al., 2020 ; Khanna et al., 2010 ; Koyama et al., 2013 ; Li et al., 2015 ; Piekna-Przybylska et al., 2017 ). Moreover, the role of DSB in the course of these infections has only been studied using mitotic cells.…”

Section: Introductionmentioning

confidence: 99%

Borna disease virus docks on neuronal DNA double-strand breaks to replicate and dampens neuronal activity

et al. 2022

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Summary Borna disease viruses (BoDV) have recently emerged as zoonotic neurotropic pathogens. These persistent RNA viruses assemble nuclear replication centers (vSPOT) in close interaction with the host chromatin. However, the topology of this interaction and its consequences on neuronal function remain unexplored. In neurons, DNA double-strand breaks (DSB) have been identified as novel epigenetic mechanisms regulating neurotransmission and cognition. Activity-dependent DSB contribute critically to neuronal plasticity processes, which could be impaired upon infection. Here, we show that BoDV-1 infection, or the singled-out expression of viral Nucleoprotein and Phosphoprotein, increases neuronal DSB levels. Of interest, inducing DSB promoted the recruitment anew of vSPOT colocalized with DSB and increased viral RNA replication. BoDV-1 persistence decreased neuronal activity and response to stimulation by dampening the surface expression of glutamate receptors. Taken together, our results propose an original mechanistic cross talk between persistence of an RNA virus and neuronal function, through the control of DSB levels.

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Detection of Influenza Virus Induced Ultrastructural Changes and DNA Damage

Cited by 7 publications

References 26 publications

Influenza infection induces host DNA damage and dynamic DNA damage responses during tissue regeneration

Influenza infection induces host DNA damage and dynamic DNA damage responses during tissue regeneration

DNA mismatch repair is required for the host innate response and controls cellular fate after influenza virus infection

Borna disease virus docks on neuronal DNA double-strand breaks to replicate and dampens neuronal activity

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