Qualitative Differences Between the IFNα subtypes and IFNβ Influence Chronic Mucosal HIV-1 Pathogenesis

Guo, Kejun; Shen, Guannan; Kibbie, Jon; González, Tània; Dillon, Stephanie M.; Smith, Harry A.; Cooper, Emily; Lavender, Kerry J.; Hasenkrug, Kim J.; Sutter, Kathrin; Dittmer, Ulf; Kroehl, Miranda; Kechris, Katerina; Wilson, Cara C.; Santiago, Mario L.

doi:10.1371/journal.ppat.1008986

Cited by 27 publications

(72 citation statements)

References 99 publications

(155 reference statements)

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“…We reported that HIV-1 inhibition by the IFNα subtypes correlated with IFNΑR signaling capacity and binding affinity to the IFNΑR2 subunit 3,23 . IFNΑR signaling capacity, as measured in an IFNsensitive reporter cell line (iLite cells; Euro Diagnostics), correlated with the antiviral potencies of the IFNα subtypes against SARS-CoV-2 lineages A and B, but not B.1, B.1.351 or B.1.1.7 strains (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…1b). We normalized the IFNs based on molar concentrations similar to our previous work with HIV-1 3,23 . For rapid and robust evaluation of antiviral activities against live SARS-CoV-2 isolates, we utilized a quantitative PCR approach ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Nebulized IFNβ showed potential as a therapeutic against COVID-19 11 , and our data confirm IFNβ as a highly potent antiviral against SARS-CoV-2. However, IFNβ was also linked to pathogenic outcomes in chronic mucosal HIV-1 23 , murine LCMV 27 and if administered late in mice, SARS-CoV-1 and MERS-CoV 28,29 infection. By contrast, IFNα8 altered 3-fold less genes in primary mucosal lymphocytes than IFNβ 23 , but showed similar anti-SARS-CoV-2 potency as IFNβ.…”

Section: Discussionmentioning

confidence: 99%

“…However, IFNβ was also linked to pathogenic outcomes in chronic mucosal HIV-1 23 , murine LCMV 27 and if administered late in mice, SARS-CoV-1 and MERS-CoV 28,29 infection. By contrast, IFNα8 altered 3-fold less genes in primary mucosal lymphocytes than IFNβ 23 , but showed similar anti-SARS-CoV-2 potency as IFNβ. IFNα8 also exhibited high antiviral activity against HIV-1 3 , raising its potential for treatment against both pandemic viruses.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to the IFN-Is (12 IFNα subtypes, IFNβ and IFNω), we also evaluated 3 IFNλ subtypes (IFNλ1, IFNλ2, IFNλ3). To normalize the IFNs, we used molar concentrations 23 ( Supplementary Fig. 1c).…”

Section: Antiviral Inhibition Assaymentioning

confidence: 99%

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Interferon Resistance of Emerging SARS-CoV-2 Variants

Guo

Barrett

Mickens

et al. 2021

Preprint

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The emergence of SARS-CoV-2 variants with enhanced transmissibility, pathogenesis and resistance to vaccines presents urgent challenges for curbing the COVID-19 pandemic. While Spike mutations that enhance virus infectivity may drive the emergence of these novel variants, studies documenting a critical a role for interferon responses in the early control of SARS-CoV-2 infection, combined with the presence of viral genes that limit these responses, suggest that interferons may also influence SARS-CoV-2 evolution. Here, we compared the potency of 17 different human interferons against 5 viral lineages sampled during the course of the global outbreak that included ancestral and emerging variants. Our data revealed increased interferon resistance in emerging SARS-CoV-2 variants, indicating that evasion of innate immunity is a significant driving force for SARS-CoV-2 evolution. These findings have implications for the increased lethality of emerging variants and highlight the interferon subtypes that may be most successful in the treatment of early infections.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Antiviral Inhibition Assaymentioning

confidence: 99%

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Interferon Resistance of Emerging SARS-CoV-2 Variants

Guo

Barrett

Mickens

et al. 2021

Preprint

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Heterogeneity and functions of the 13 IFN‐α subtypes – lucky for some?

et al. 2023

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Type I IFNs are critical for host responses to viral infection and are also implicated in the pathogenesis of multiple autoimmune diseases. Multiple subtypes exist within the type I IFN family, in particular 13 distinct IFN‐α genes, which signal through the same heterodimer receptor that is ubiquitously expressed by mammalian cells. Both evolutionary genetic studies and functional antiviral assays strongly suggest differential functions and activity between the 13 IFN‐α subtypes, yet we still lack a clear understanding of these different roles. This review summarizes the evidence from studies describing differential functions of IFN‐α subtypes and highlights potential reasons for discrepancies between the reports. We examine both acute and chronic viral infection, as well as autoimmunity, and integrate a more recent awareness of the importance of anti‐IFN‐α autoantibodies in shaping the type I IFN responses in these different conditions.

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