2. Academic Validation
  3. Monkeypox virus replication and host response in vaginal and ectocervical epithelial cells

Monkeypox virus replication and host response in vaginal and ectocervical epithelial cells

  • Virulence. 2026 Dec;17(1):2649986. doi: 10.1080/21505594.2026.2649986.
Davide Mariotti 1,  Ludovica Picarone 2,  Alessandra D'Auria 3,  Luigi Rosa 1,  Valentina Valeriani 1,  Daniele Pietrucci 2,  Silvia Meschi 1,  Fabrizio Carletti 1,  Valentina Mazzotta 4,  Guido Antonelli 3,  Enrico Girardi 5,  Carolina Scagnolari 3,  Giovanni Chillemi 6 7,  Andrea Antinori 4,  Fabrizio Maggi 1,  Giulia Matusali 1 8
Affiliations

Affiliations

  • 1 Laboratory of Virology, National Institute for Infectious Diseases "Lazzaro Spallanzani"-IRCCS, Rome, Italy.
  • 2 Department for Innovation in Biological, Agro-Food and Forest Systems, University of Tuscia, Viterbo, Italy.
  • 3 Department of Molecular Medicine, Lab. of Virology, Sapienza University of Rome, affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Bolognetti, Rome, Italy.
  • 4 Clinical and Research Department, National Institute for Infectious Diseases "Lazzaro Spallanzani"- IRCSS, Rome, Italy.
  • 5 Scientific Direction, National Institute for Infectious Diseases "Lazzaro Spallanzani"- IRCSS, Rome, Italy.
  • 6 Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy.
  • 7 Bioinformatics Research Unit, National Institute for Infectious Diseases "Lazzaro Spallanzani"- IRCCS, Rome, Italy.
  • 8 Department of Biology and Biotechnology "Charles Darwin", Sapienza University of Rome, Rome, Italy.
PMID: 41880196 DOI: 10.1080/21505594.2026.2649986
Abstract

Recent mpox outbreaks have shown a predominant transmission through sexual contact. Replication-competent virus has been detected in seminal fluid, while in female patients, vaginal lesions, vertical transmission, and miscarriage risk have been reported. This study explored the susceptibility of the lower female genital tract (LFGT) to monkeypox virus (MPXV) Infection, the role of sex-hormones in modulating viral replication, and host-virus molecular interactions. Human vaginal (VK2/E6E7) and ectocervical (Ect1/E6E7) epithelial cells were exposed to MPXV clade IIb, and viral replication was assessed. The influence of sex-hormones was evaluated after pretreatment with physiological concentrations of 17-β-estradiol or progesterone. Cellular genes' expression was determined by RT-qPCR and RNAseq, and ELISA was used for protein release analysis. Both cell lines supported productive MPXV Infection. 17-β -estradiol and progesterone slightly reduced viral replication in Ect1/E6E7. At 48 hours post-infection, compared to uninfected control, 216 differentially expressed genes (DEGs) were identified in MPXV infected VK2/E6E7 and 11 in Ect1/E6E7, with nine shared DEGs involved in protein folding (HSPA6), chemotaxis (CXCL3, ARC), inflammation and lymphoproliferation (IL11, IL1RL1, MMP-1), and tissue remodeling (IGFN1, MMP-1). MPXV Infection significantly increased MMP-1 release in both cell lines, and MMP-1 inhibitors reduced infectious virus production. IFN-β and IFN-λ1 were induced earlier and more pronouncedly in Ect1/E6E7 which also showed slower viral replication than VK2/E6E7. Our analysis demonstrated the MPXV-mediated modulation of common and tissue-specific cellular pathways in the LFGT. The perturbation of tissue remodeling and inflammation in this district has the potential to affect reproductive health and susceptibility to sexually-transmitted-infections.

Keywords

Monkeypox virus; antiviral response; emerging viruses; female genital tract; sexually transmitted viruses.

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