Magnitude and timing of the antiviral response determine SARS-CoV-2 replication early in infection

Cheemarla, Nagarjuna R.; Watkins, Timothy A.; Mihaylova, Valia T.; Wang, Bao; Zhao, Dejian; Wang, Guilin; Landry, Marie L.; Foxman, Ellen F.

doi:10.1101/2021.01.22.21249812

Cited by 10 publications

(5 citation statements)

References 77 publications

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“…Using a similar experimental design, our preliminary in vitro infection model suggested that prior RV-A16 infection could suppress SARS-CoV-2 replication using HBEC (Supplementary Figure 4). A recent finding suggested that the protective effect conferred by prior EV exposure in respiratory cells is again due to the induction on IFN-stimulated genes shared high consistency with our findings 26 .…”

Section: Discussionsupporting

confidence: 92%

Suppression of influenza virus infection by rhinovirus interference at the population, individual and cellular levels

Tao

Chong

Pun

et al. 2021

Preprint

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Background: Investigations of the natural viral interference effect between rhinovirus (RV) and influenza virus (IV) were conducted in temperate regions. We conducted an epidemiological study in Hong Kong, a major epicentre of influenza virus in the sub-tropical region. RV is the most prevalent respiratory virus year-round and causes asymptomatic to mild symptoms while IV infection exerts a great burden of public health. We aimed to examine the correlation of RV prevalence against IV activity. Methods: Nasopharyngeal aspirates (NPA) collected from patients hospitalized in the regional hospitals from 2015 to 2019 were examined for the presence of respiratory viruses. The correlation of the monthly prevalence between all pairs of virus infection, the co-infection rate and the temporal interference of RV and IV were tested. The viral interference was validated in vitro by conducting sequential RV and IV infection in the well-differentiated primary human airway epithelial cells. Findings: A total of 112,926 NPA were evaluated, and the Enterovirus/RV was the most prevalent respiratory virus detected. The negative correlation between EV/RV and IVs prevalence was independent of age and meteorological factors. Co-infection of EV/RV and IV was significantly less when compared with other virus pairs. Prior exposure to RV inhibited the replication of influenza A, B and oseltamivir-resistance stain in vitro and the inhibition is replication dependent. Interpretation: Epidemiological surveillance and the sequential infection in vitro suggested viral interference between EV/RV and IV operated at the population, individual and cellular levels.

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Section: Discussionsupporting

confidence: 92%

Suppression of influenza virus infection by rhinovirus interference at the population, individual and cellular levels

Tao

Chong

Pun

et al. 2021

Preprint

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“…The interplay between IFNs and COVID-19 disease progression is complex, and despite initial findings, there is currently no clear evidence for a genetic immune predisposition to severe COVID-19 (Meisel et al, 2021;Povysil et al, 2021). Nevertheless, there is evidence at early iScience Article stages of infection that SARS-CoV-2 is sensitive to ISG induction and IFNs are being discussed as a treatment option (Cheemarla et al, 2021;Hasselbalch et al, 2021;Yang et al, 2021). In this light, our findings could inform future therapeutic approaches.…”

Section: Discussionmentioning

confidence: 77%

The circadian clock component BMAL1 regulates SARS-CoV-2 entry and replication in lung epithelial cells

Zhuang¹,

Tsukuda²,

Wrensch³

et al. 2021

iScience

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The COVID-19 pandemic, caused by SARS-CoV-2 coronavirus, is a global health issue with unprecedented challenges for public health. SARS-CoV-2 primarily infects cells of the respiratory tract via Spike glycoprotein binding to angiotensin-converting enzyme (ACE2). Circadian rhythms coordinate an organism’s response to its environment and can regulate host susceptibility to virus infection. We demonstrate that silencing the circadian regulator Bmal1 or treating lung epithelial cells with the REV-ERB agonist SR9009 reduce ACE2 expression and inhibit SARS-CoV-2 entry and replication. Importantly, treating infected cells with SR9009 limits SARS-CoV-2 replication and secretion of infectious particles, showing that post-entry steps in the viral life cycle are influenced by the circadian system. Transcriptome analysis revealed that Bmal1 silencing induced interferon stimulated gene transcripts in Calu-3 lung epithelial cells, providing a mechanism for the circadian pathway to limit SARS-CoV-2 infection. Our study highlights alternative approaches to understand and improve therapeutic targeting of SARS-CoV-2.

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“…Type I IFNs (IFN-α and IFN-β) and type III IFNs (IFN-λ) provide potent antiviral immunity against SARS-CoV-2 via ISG protein expression [30][31][32] . However, SARS-CoV-2 replication is more rapid than the antiviral IFN responses at a higher viral load 33 . Under these conditions, the IFN responses cannot limit viral replication and may induce inflammatory responses, thereby causing tissue damage 31 .…”

Section: Discussionmentioning

confidence: 99%

Hemin as a novel candidate for treating COVID-19 via heme oxygenase-1 induction

Kim

Ahn

et al. 2021

Sci Rep

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease-19 (COVID-19). More than 143 million cases of COVID-19 have been reported to date, with the global death rate at 2.13%. Currently, there are no licensed therapeutics for controlling SARS-CoV-2 infection. The antiviral effects of heme oxygenase-1 (HO-1), a cytoprotective enzyme that inhibits the inflammatory response and reduces oxidative stress, have been investigated in several viral infections. To confirm whether HO-1 suppresses SARS-CoV-2 infection, we assessed the antiviral activity of hemin, an effective and safe HO-1 inducer, in SARS-CoV-2 infection. We found that treatment with hemin efficiently suppressed SARS-CoV-2 replication (selectivity index: 249.7012). Besides, the transient expression of HO-1 using an expression vector also suppressed the growth of the virus in cells. Free iron and biliverdin, which are metabolic byproducts of heme catalysis by HO-1, also suppressed the viral infection. Additionally, hemin indirectly increased the expression of interferon-stimulated proteins known to restrict SARS-CoV-2 replication. Overall, the findings suggested that HO-1, induced by hemin, effectively suppressed SARS-CoV-2 in vitro. Therefore, HO-1 could be potential therapeutic candidate for COVID-19.

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Magnitude and timing of the antiviral response determine SARS-CoV-2 replication early in infection

Cited by 10 publications

References 77 publications

Suppression of influenza virus infection by rhinovirus interference at the population, individual and cellular levels

Suppression of influenza virus infection by rhinovirus interference at the population, individual and cellular levels

The circadian clock component BMAL1 regulates SARS-CoV-2 entry and replication in lung epithelial cells

Hemin as a novel candidate for treating COVID-19 via heme oxygenase-1 induction

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