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Antiviral factors and type I/III interferon expression associated with regulatory factors in the oral epithelial cells from HIV-1-serodiscordant couples.

Cervantes CA, Oliveira LM, Manfrere KC, Lima JF, Pereira NZ, Duarte AJ, Sato MN - Sci Rep (2016)

Bottom Line: Innate and adaptive immunity, as well as genetic factors, provide ESNs with important advantages that allow for low infection susceptibility.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.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil.

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.

No MeSH data available.


Related in: MedlinePlus

The upregulation of antiviral factor expression in the mucosal oral epithelial cells of serodiscordant couples.The mRNA expression levels of (A) A3G, Trex, Foxo3 and (B) IFN-α, IFN-β and IFN-λ are shown. (C) Correlations between ESN IFN-β expression and antiviral factors are presented. Cells from buccal washes were obtained from healthy controls (HCs, n = 10–14), exposed seronegative individuals (ESNs, n = 11–15) and HIV-1-infected partners (n = 11–15), and assessed by real-time PCR. The data represent the median values. *p ≤ 0.05.
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f3: The upregulation of antiviral factor expression in the mucosal oral epithelial cells of serodiscordant couples.The mRNA expression levels of (A) A3G, Trex, Foxo3 and (B) IFN-α, IFN-β and IFN-λ are shown. (C) Correlations between ESN IFN-β expression and antiviral factors are presented. Cells from buccal washes were obtained from healthy controls (HCs, n = 10–14), exposed seronegative individuals (ESNs, n = 11–15) and HIV-1-infected partners (n = 11–15), and assessed by real-time PCR. The data represent the median values. *p ≤ 0.05.

Mentions: Notably, we detected a similar mRNA expression profile of antiviral factors in both ESN and HIV-infected partners (Fig. 3). Serodiscordant couples exhibited increased A3G and IFN-β expression levels compared to HC individuals. IFN-α expression was increased in ESNs, and IFN-λ (type III IFN) was increased in HIV-1-infected individuals compared to HC individuals, although some serodiscordant samples were equally upregulated. The increased antiviral factor expression in the ESN group did not correlate with the VL status of their HIV-infected partner. We could not detect some antiviral factors in buccal epithelial cells, such as TRIM5-α, SAMDH1, STING and the regulatory factors Socs3, TBk1 and IL-10.


Antiviral factors and type I/III interferon expression associated with regulatory factors in the oral epithelial cells from HIV-1-serodiscordant couples.

Cervantes CA, Oliveira LM, Manfrere KC, Lima JF, Pereira NZ, Duarte AJ, Sato MN - Sci Rep (2016)

The upregulation of antiviral factor expression in the mucosal oral epithelial cells of serodiscordant couples.The mRNA expression levels of (A) A3G, Trex, Foxo3 and (B) IFN-α, IFN-β and IFN-λ are shown. (C) Correlations between ESN IFN-β expression and antiviral factors are presented. Cells from buccal washes were obtained from healthy controls (HCs, n = 10–14), exposed seronegative individuals (ESNs, n = 11–15) and HIV-1-infected partners (n = 11–15), and assessed by real-time PCR. The data represent the median values. *p ≤ 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4863167&req=5

f3: The upregulation of antiviral factor expression in the mucosal oral epithelial cells of serodiscordant couples.The mRNA expression levels of (A) A3G, Trex, Foxo3 and (B) IFN-α, IFN-β and IFN-λ are shown. (C) Correlations between ESN IFN-β expression and antiviral factors are presented. Cells from buccal washes were obtained from healthy controls (HCs, n = 10–14), exposed seronegative individuals (ESNs, n = 11–15) and HIV-1-infected partners (n = 11–15), and assessed by real-time PCR. The data represent the median values. *p ≤ 0.05.
Mentions: Notably, we detected a similar mRNA expression profile of antiviral factors in both ESN and HIV-infected partners (Fig. 3). Serodiscordant couples exhibited increased A3G and IFN-β expression levels compared to HC individuals. IFN-α expression was increased in ESNs, and IFN-λ (type III IFN) was increased in HIV-1-infected individuals compared to HC individuals, although some serodiscordant samples were equally upregulated. The increased antiviral factor expression in the ESN group did not correlate with the VL status of their HIV-infected partner. We could not detect some antiviral factors in buccal epithelial cells, such as TRIM5-α, SAMDH1, STING and the regulatory factors Socs3, TBk1 and IL-10.

Bottom Line: Innate and adaptive immunity, as well as genetic factors, provide ESNs with important advantages that allow for low infection susceptibility.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.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil.

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.

No MeSH data available.


Related in: MedlinePlus