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About the Authors:
Andrea Introini
* E-mail: [email protected]
Affiliation: Unit of Infectious Diseases, Center for Molecular Medicine, Department of Medicine Solna, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden
ORCID http://orcid.org/0000-0002-9929-8964
Stéphanie Boström
Affiliation: Unit of Infectious Diseases, Center for Molecular Medicine, Department of Medicine Solna, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden
Frideborg Bradley
Affiliation: Unit of Infectious Diseases, Center for Molecular Medicine, Department of Medicine Solna, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden
Anna Gibbs
Affiliation: Unit of Infectious Diseases, Center for Molecular Medicine, Department of Medicine Solna, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden
Axel Glaessgen
Affiliation: Department of Clinical Pathology and Cytology, Unilabs AB, Capio St Göran Hospital, Stockholm, Sweden
Annelie Tjernlund
Affiliation: Unit of Infectious Diseases, Center for Molecular Medicine, Department of Medicine Solna, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden
Kristina Broliden
Affiliation: Unit of Infectious Diseases, Center for Molecular Medicine, Department of Medicine Solna, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, SwedenAbstract
The most immediate and evident effect of mucosal exposure to semen in vivo is a local release of proinflammatory mediators accompanied by an influx of leukocytes into the female genital mucosa (FGM). The implication of such response in HIV-1 transmission has never been addressed due to limitations of currently available experimental models. Using human tissue explants from the uterine cervix, we developed a system of mucosal exposure to seminal plasma (SP) that supports HIV-1 replication. Treatment of ectocervical explants with SP resulted in the upregulation of inflammatory and growth factors, including IL-6, TNF, CCL5, CCL20, CXCL1, and CXCL8, and IL1A, CSF2, IL7, PTGS2, as evaluated by measuring protein levels in explant conditioned medium (ECM) and gene expression in tissue. SP treatment was also associated with increased recruitment of monocytes and neutrophils, as observed upon incubation of peripheral blood leukocytes with ECM in a transwell system. To evaluate the impact of the SP-mediated response on local susceptibility to HIV-1, we infected ectocervical explants with the CCR5-tropic variant HIV-1BaL either in the presence of SP, or after explant pre-incubation with SP. In both experimental settings SP enhanced virus replication as evaluated by HIV-1 p24gag released in explant culture medium over time, as well as by HIV-1 DNA quantification in explants infected in the presence...