MPXV infection impairs IFN response but is partially sensitive to IFN-γ antiviral effect.

Autor: Bordi L; Laboratory of Virology, National Institute for Infectious Diseases 'Lazzaro Spallanzani' IRCCS, Rome, Italy., D'Auria A; Department of Molecular Medicine, Laboratory of Virology, Sapienza University of Rome, Rome, Italy., Frasca F; Department of Molecular Medicine, Laboratory of Virology, Sapienza University of Rome, Rome, Italy.; Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy., Mazzotta V; Clinical Department, National Institute for Infectious Diseases 'Lazzaro Spallanzani' IRCCS, Rome, Italy., Mazzetti P; Department of Translational Research, Virology Section and Retrovirus Centre, University of Pisa, Pisa, Italy., Fracella M; Department of Molecular Medicine, Laboratory of Virology, Sapienza University of Rome, Rome, Italy., d'Ettorre G; Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy., Antonelli G; Department of Molecular Medicine, Laboratory of Virology, Sapienza University of Rome, Rome, Italy., Pistello M; Department of Translational Research, Virology Section and Retrovirus Centre, University of Pisa, Pisa, Italy., Antinori A; Clinical Department, National Institute for Infectious Diseases 'Lazzaro Spallanzani' IRCCS, Rome, Italy., Viscidi RP; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Maggi F; Laboratory of Virology, National Institute for Infectious Diseases 'Lazzaro Spallanzani' IRCCS, Rome, Italy., Lalle E; Laboratory of Virology, National Institute for Infectious Diseases 'Lazzaro Spallanzani' IRCCS, Rome, Italy., Scagnolari C; Department of Molecular Medicine, Laboratory of Virology, Sapienza University of Rome, Rome, Italy. carolina.scagnolari@uniroma1.it.
Jazyk: angličtina
Zdroj: Medical microbiology and immunology [Med Microbiol Immunol] 2024 Nov 11; Vol. 213 (1), pp. 25. Date of Electronic Publication: 2024 Nov 11.
DOI: 10.1007/s00430-024-00808-w
Abstrakt: The recent outbreak of monkeypox virus (MPXV) has caused global concern. How the virus evades the interferon (IFN) response is still poorly understood. We analyzed type I/II IFN (IFN-I/II) expression in clinical samples from MPXV-infected patients and measured IFN-I kinetics in MPXV-infected cells. We also evaluated the anti-MPXV activity of IFN-I/II in A549, HeLa and Vero-E6 cell lines. IFN-I/II mRNA expression was detected in skin lesions, anal swabs, nasopharyngeal samples and peripheral blood mononuclear cells (PBMC), with the highest levels in skin lesions (p < 0.05). High MPXV DNA levels in clinical samples were associated with increased IFN-I levels. In vitro, MPXV infection induced a peak of IFN-I between 48 and 72 h post-infection (p < 0.01). Pre-treatment of the A549, HeLa and Vero-E6 cells with high concentrations (≥ 100,000 International Unit, IU/ml) of IFN-α and IFN-ω did not inhibit or had little effect on MPXV replication, while IFN-β moderately reduced MPXV replication by 2.7-1.5 log 10 at 100,000 IU/ml. In clinical samples there was a trend for elevated levels of IFN-γ in association with lower MPXV load and in vitro IFN-γ (3,600 IU/ml) strongly reduced viral titers by 3.4-1.6 log 10 . There were no significant differences in expression of select IFN-stimulated genes (ISGs) in MPXV infection in vitro. This study shows that MPXV delays IFN-I induction and inhibits expression of selected ISGs in vitro and is associated with an IFN-I resistance phenotype in vivo. However, MPXV is less resistant to IFN-γ in vivo and is sensitive to IFN-γ treatment in vitro, suggesting a potential therapeutic role for IFN-γ.
Competing Interests: Declarations Ethical approval This study used samples collected from MPXV infected patients in accordance with the Ethical approval at the University of Rome Sapienza, Policlinico Umberto I Hospital, Italy (STI: Rif.6963, Prot.0951/2022). Competing interests The authors declare no competing interests.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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