title: Antiviral factors and type I/III interferon expression associated with regulatory factors in the oral epithelial cells from HIV-1-serodiscordant couples.
abstract: Individuals who remain HIV-seronegative despite repeated unprotected exposure to the virus are defined as exposed seronegative (ESN) individuals. Innate and adaptive immunity, as well as genetic factors, provide ESNs with important advantages that allow for low infection susceptibility. The majority of HIV-1-infected individuals undergo antiretroviral therapy, which can decrease the level of HIV-1 exposure in ESNs. We analyzed type I interferon (IFN)-related antiviral and regulatory factors in peripheral blood mononuclear cells (PBMCs) and oral epithelial cells from serodiscordant couples. Our findings revealed that ESNs did not induce the expression of antiviral factors (APOBEC-3G, TRIM5-α, SAMDH1, STING, TBk1) or regulatory factors (Trex, Foxo3, Socs3, IL-10) in PBMCs, unlike their HIV-1-infected partners. In contrast, ESNs upregulated APOBEC-3G and type I/III IFNs (IFNs-α,-β/-λ) in oral mucosal epithelial cells similar to their HIV-infected partners. The serodiscordant groups exhibited an increased expression of type I IFN-induced regulators, such as Trex and Foxo3, in oral epithelial cells. TLR7, TLR8 and TLR9 were expressed in oral epithelial cells of both ESNs and HIV-1-infected subjects. These findings revealed evidence of antiviral factors, type I/III interferon and regulatory factor expression only in the oral mucosal compartment of ESNs, while HIV-1-infected partners systemically and oral mucosal expressed the antiviral profile.
authors.affiliation: Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Cesar A C
authors.initials: CA
authors.lastname: Cervantes
authors.affiliation: Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Luanda M S
authors.initials: LM
authors.lastname: Oliveira
authors.affiliation: Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Kelly C G
authors.initials: KC
authors.lastname: Manfrere
authors.affiliation: Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Josenilson F
authors.initials: JF
authors.lastname: Lima
authors.affiliation: Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Natalli Z
authors.initials: NZ
authors.lastname: Pereira
authors.affiliation: Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Alberto J S
authors.initials: AJ
authors.lastname: Duarte
authors.affiliation: Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Maria N
authors.initials: MN
authors.lastname: Sato
mesh_terms: D056704:Adaptive Immunity; D000328:Adult; D000998:Antiviral Agents / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000821:virology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D018023:HIV Seronegativity; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism*; D016899:Interferon-beta / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008297:Male; D008875:Middle Aged; D009055:Mouth / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D012747:Sexual Partners
chemical_list: D000998:Antiviral Agents; C573415:IFNG protein, human; D016898:Interferon-alpha; D016899:Interferon-beta; D007371:Interferon-gamma