ABSTRACT
BACKGROUND: Several soluble factors have been reported to have the capacity of inhibiting HIV replication at different steps of the virus life cycle, without eliminating infected cells and through enhancement of specific cellular mechanisms. Yet, it is unclear if these antiviral factors play a role in the protection from HIV infection or in the control of viral replication. Here we evaluated two cohorts: i) one of 58 HIV-exposed seronegative individuals (HESNs) who were compared with 59 healthy controls (HCs), and ii) another of 13 HIV-controllers who were compared with 20 HIV-progressors. Peripheral blood, oral and genital mucosa and gut-associated lymphoid tissue (GALT) samples were obtained to analyze the mRNA expression of ELAFIN, APOBEC3G, SAMHD1, TRIM5α, RNase 7 and SerpinA1 using real-time PCR. RESULTS: HESNs exhibited higher expression of all antiviral factors in peripheral blood mononuclear cells (PBMCs), oral or genital mucosa when compared with HCs. Furthermore, HIV-controllers exhibited higher levels of SerpinA1 in GALT. CONCLUSIONS: These findings suggest that the activity of these factors is compartmentalized and that these proteins have a predominant role depending on the tissue to avoid the infection, reduce the viral load and modulate the susceptibility to HIV infection.
Subject(s)
HIV Infections/immunology , HIV Infections/prevention & control , Adult , Aminohydrolases/genetics , Aminohydrolases/immunology , Antiviral Agents/immunology , Antiviral Restriction Factors , Carrier Proteins/genetics , Carrier Proteins/immunology , Case-Control Studies , Cohort Studies , Cross-Sectional Studies , Disease Progression , Elafin/genetics , Elafin/immunology , Female , Genitalia, Female/immunology , HIV Infections/virology , HIV Long-Term Survivors , HIV Seronegativity/immunology , Host-Pathogen Interactions/genetics , Host-Pathogen Interactions/immunology , Humans , Lymphoid Tissue/immunology , Male , Middle Aged , Monomeric GTP-Binding Proteins/genetics , Monomeric GTP-Binding Proteins/immunology , Mouth Mucosa/immunology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Ribonucleases/genetics , Ribonucleases/immunology , SAM Domain and HD Domain-Containing Protein 1 , Tripartite Motif Proteins , Ubiquitin-Protein Ligases , Virus Replication/immunology , Young Adult , alpha 1-Antitrypsin/genetics , alpha 1-Antitrypsin/immunologyABSTRACT
We evaluated the reliability of IgA and IgG antigliadin antibodies (AGA-A, AGA-G), antireticulin antibody (ARA), endomysial antibodies (EmA), and alpha 1-antitrypsin clearance (alpha 1-AT CL) in the detection of celiac sprue (CS) in 59 first-degree asymptomatic relatives of celiac patients who had duodenal biopsy. Twenty-four relatives who had normal results of screening tests were selected at random for biopsy; 35 relatives with at least one abnormal test result were biopsied. Eleven relatives were noted to have villous atrophy at biopsy; the diagnosis of celiac sprue was confirmed by histological improvement after gluten-free diet in six. AGA-G, alpha 1-AT CL, and EmA had sensitivities of 73%, 73%, and 64%, respectively, with very high levels of specificity. Sensitivity was improved by the combination of two serological markers (AGA-G + alpha 1-AT CL = 91%; AGA-G + EmA = 82%; EmA + ARA = 82%). Furthermore, combination of EmA and ARA has shown the best specificity and positive predictive value. AGA-G, alpha 1-AT CL, and EmA are reliable individual markers for the detection of asymptomatic celiac sprue. However, a combination of two of them, including ARA, was more sensitive than the individual tests.