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Amandine Gagneux-Brunon, Nicolas Rochereau, Elisabeth Botelho-Nevers, Frédéric Lucht, Bruno Pozzetto, Stéphane Paul, Thomas Bourlet
Most new HIV infections occur via sexual routes. The induction of protective anti-HIV antibodies in genital mucosa is an important step towards reducing HIV transmission. Mucosal anti-HIV antibodies may play a dual role by either protecting against HIV transmission or facilitating it. Protective properties against HIV of mucosal IgGs and IgAs exhibiting neutralizing or antibody dependent cell-mediated cytotoxicity (ADCC) activities have been described in highly exposed seronegative individuals (HESN). Conversely, some IgGs may facilitate the crossing of HIV free particles through epithelial barriers by transcytosis...
March 18, 2017: AIDS
V Thibodeau, L Fourcade, A-C Labbé, M Alary, F Guédou, J Poudrier, M Roger
We and others have shown that HIV-1 highly-exposed seronegative (HESN) female commercial sex workers (CSWs) maintain low genital inflammatory conditions to prevent HIV infection. HIV-1 interacts with toll-like receptors (TLR)-7/8 to induce interferon (IFN)-α, an important antiviral and immunomodulatory cytokine, which act together with interleukin (IL)-10, human leukocyte antigen (HLA)-G and immunoglobulin-like transcript (ILT)-4 to initiate a "tolerogenic/regulatory" anti-inflammatory loop. In view of further unravelling elements associated with natural immunity to HIV-1, we have characterised TLR-7, IFN-α, IL-10, HLA-G and ILT-4 expression profiles in the genital tract of female CSWs and HIV-1-uninfected non-CSWs from Benin...
March 6, 2017: Scientific Reports
Wbeimar Aguilar-Jimenez, Irma Saulle, Daria Trabattoni, Francesca Vichi, Sergio Lo Caputo, Francesco Mazzotta, Maria T Rugeles, Mario Clerici, Mara Biasin
Natural resistance to HIV-1 infection is influenced by genetics, viral-exposure, and endogenous immunomodulators such as vitamin D (VitD), being a multifactorial phenomenon that characterizes HIV-1-exposed seronegative individuals (HESNs). We compared mRNA expression of 10 antivirals, 5 immunoregulators, and 3 VitD pathway genes by qRT-PCR in cells of a small cohort of 11 HESNs, 16 healthy-controls (HCs), and 11 seropositives (SPs) at baseline, in response to calcidiol (VitD precursor) and/or aldithriol-2-(AT2)-inactivated HIV-1...
2017: Frontiers in Immunology
N Rallón, C Restrepo, J L Vicario, J Del Romero, C Rodríguez, J García-Samaniego, M García, A Cabello, M Górgolas, J M Benito
OBJECTIVES: The objective of this study was to seek correlates of immune protection in HIV infection. We sought to elucidate the association between the presence of human leucocyte antigen (HLA) alleles, as well as killer immunoglobulin receptor (KIR) genotypes, and the susceptibility to HIV infection in a Spanish cohort of HIV-exposed seronegative (HESN) individuals. METHODS: A total of 152 individuals were evaluated: 29 HESN individuals in stable heterosexual relationships with an HIV-infected partner admitting high-risk sexual intercourse for at least 12 months prior to inclusion in the study, 61 HIV-infected patients and 62 healthy controls...
February 20, 2017: HIV Medicine
T Leu, S Rauthe, C Wirth, H-U Simon, V Kunzmann, H Hebestreit, S Kunzmann
Based on a case report an overview on the differential diagnostic considerations with respect to blood hypereosinophilia (HE) and hypereosinophilic syndromes (HES) in childhood is given. A 13-year-old boy was admitted for the clarification of an asthma. In the blood count an increased HE with 3 500/µl (30%) was found along with elevated total serum IgE and IL-5 level (2 000 IU/ml and 17 pg/ml). Lung function showed an obstruction (FEV1 38%). Radiologically the picture of bronchiectasis and mucus pluggine appeared...
November 2016: Klinische Pädiatrie
Sophia Osawe, Evaezi Okpokoro, Ruth Datiri, Grace Choji, Felicia Okolo, Pam Datong, Alash'le Abimiku
BACKGROUND: HIV/AIDS continues to be a global health problem. With currently no cure, it is critical to get an effective vaccine to add to the arsenal of prevention and treatment tools. HIV Exposed Sero-Negative (HESN) individuals were enrolled and followed for 2 years. METHODS: A prospective observational cohort study to enroll HESN volunteers and their partners was developed with a 2-year follow up. This was a vaccine preparedness study and designed as a Phase IIb trial...
2016: BMC Infectious Diseases
Daria Trabattoni, Federica Gnudi, Salomè V Ibba, Irma Saulle, Simone Agostini, Michela Masetti, Mara Biasin, Jean-Francois Rossignol, Mario Clerici
Nitazoxanide (Alinia(®), NTZ) and tizoxanide (TIZ), its active circulating metabolite, belong to a class of agents known as thiazolides (TZD) endowed with broad anti-infective activities. TIZ and RM-4848, the active metabolite of RM-5038, were shown to stimulate innate immunity in vitro. Because natural resistance to HIV-1 infection in HIV-exposed seronegative (HESN) individuals is suggested to be associated with strong innate immune responses, we verified whether TIZ and RM-4848 could reduce the in vitro infectiousness of HIV-1...
2016: Scientific Reports
Sara Yahyaei, Mara Biasin, Irma Saulle, Federica Gnudi, Mariacristina De Luca, Karen I Tasca, Daria Trabattoni, Sergio Lo Caputo, Francesco Mazzotta, Mario Clerici
OBJECTIVE: MicroRNAs (miRNAs) are small noncoding RNAs involved in the posttranscriptional regulation of gene expression that play important roles in viral infections. Alterations of specific miRNAs are described in HIV infection, suggesting a role for miRNAs in pathogenesis of this disease. We verified whether a particular miRNA signature could be identified in natural resistance to HIV-1. METHODS: Expression level of 84 miRNAs was analyzed by RT-qPCR in plasma and unstimulated peripheral blood mononuclear cell (PBMC) of 30 seronegative individuals repeatedly exposed to HIV-1 (HESN), 30 HIV seropositive subjects (HIV+), and 30 healthy controls (HC)...
September 1, 2016: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Wbeimar Aguilar-Jimenez, Wildeman Zapata, María T Rugeles
The relationship between the immunomodulatory effects of Vitamin D (VitD) and the expression of anti-HIV-1 molecules has not been explored in HIV-1-exposed seronegative individuals (HESNs). Higher mRNA levels of cathelicidin and HAD-4 in oral-mucosa and peripheral-blood, along with higher CYP24A1 mRNA in vaginal-mucosa and lower TLR2 mRNA in endocervical-mucosa were found in HESNs compared to non-exposed controls. Furthermore, the mRNA of anti-HIV molecules Elafin, TRIM5, Cathelicidin, HAD-4 and RNase7, previously associated with natural resistance to HIV-1 infection, positively correlated with the mRNA expression of VDR in HESNs, suggesting the potential participation of VitD in natural resistance to HIV-1...
July 2016: Microbes and Infection
Kenneth Omollo, Geneviève Boily-Larouche, Julie Lajoie, Makobu Kimani, Julianna Cheruiyot, Joshua Kimani, Julius Oyugi, Keith Raymond Fowke
BACKGROUND: Unprotected sexual intercourse exposes the female genital tract (FGT) to semen-derived antigens, which leads to a proinflammatory response. Studies have shown that this postcoital inflammatory response can lead to recruitment of activated T cells to the FGT, thereby increasing risk of HIV infection. OBJECTIVE: The purpose of this study was to evaluate the impact of sex work on activation and memory phenotypes of peripheral T cells among female sex workers (FSW) from Nairobi, Kenya...
October 2016: AIDS Research and Human Retroviruses
Jiangyang Zhao, Shangyang She, Li Xie, Xiaopei Chen, Cuiju Mo, Li Huang, Wenqian Tang, Xuejie Chen
Associations of regulated on activation, normal T cell expressed and secreted (RANTES) -403G/A, -28C/G, and In1.1T/C polymorphisms with HIV-1 infection and the progression of HIV-1 disease have been widely reported with inconsistent results. To clarify this situation, we performed an updated meta-analysis of all available studies from PubMed, EMBASE, and the China National Knowledge Infrastructure. A total of 24 eligible studies involving more than 10,000 subjects were included. By using the healthy controls, we found that -403G/A polymorphism was significantly associated with reduced susceptibility to HIV-1 infection in G/A+A/A versus GG (odds ratio [OR] = 0...
June 2016: AIDS Research and Human Retroviruses
Juan C Hernandez, Georges St Laurent, Silvio Urcuqui-Inchima
Pattern recognition receptors (PRRs) are involved in direct recognition of viruses, promoting cellular activation and the production of pro-inflammatory cytokines. However, despite the reduced systemic immune activation described in HIV-1-exposed seronegatives (HESNs), few studies have focused on determining the relationship between PRR expression and cytokine production. We have aimed here to evaluate the expression level of PRRs and cytokines in HESNs, HIV-1 patients and healthy donors. Basal PRR expression levels in PBMCs, dendritic cells (DCs) and monocytes, and plasma cytokine levels as well as the PRR ligand-induced cytokine productions were determined by flow cytometry, qPCR and ELISA...
February 2016: Immunologic Research
Wildeman Zapata, Wbeimar Aguilar-Jiménez, Zhimin Feng, Aaron Weinberg, Aniello Russo, Nicoletta Potenza, Hernando Estrada, María T Rugeles
Defensins, RNases and cytokines are present at mucosal barriers, main ports of HIV entry, and are potential mediators of the resistant phenotype exhibited by HIV-1-exposed seronegative individuals (HESN) during sexual exposure. We aimed to determine the role of soluble factors in natural resistance to HIV-1 infection. Vaginal/endocervical/oral mucosal samples were taken from 60 HESN, 60 seropositive (SP) and 61 healthy controls (HC). Human neutrophil peptide 1 (hNP-1), human beta defensin (hBD) 2 and 3, RNases, MIP-1β and RANTES mRNA transcripts were quantified by qPCR and in vitro single-round, recombinant-based viral infectivity assay was used to evaluate the anti-HIV-1 activity of hBDs and RNases...
March 2016: Microbes and Infection
Ruey-Chyi Su, Andrew Plesniarski, Zhujun Ao, Joshua Kimani, Aida Sivro, Walter Jaoko, Frank A Plummer, Xiaojian Yao, Terry Blake Ball
Cells from women who are epidemiologically deemed resistant to HIV infection exhibit a 40-60% reduction in endogenous IRF-1 (interferon regulatory factor-1), an essential regulator of host antiviral immunity and the early HIV replication. This study examined the functional consequences of reducing endogenous IRF-1 on HIV-1 replication and immune response to HIV in natural HIV target cells. IRF-1 knockdown was achieved in ex vivo CD4(+) T cells and monocytes with siRNA. IRF-1 level was assessed using flow cytometry, prior to infection with HIV-Bal, HIV-IIIB, or HIV-VSV-G...
2015: Molecular Therapy. Nucleic Acids
Íris M Santos, Elis A da Rosa, Tiago Gräf, Luiz G E Ferreira, Andrea Petry, Fernanda Cavalheiro, Edna M Reiche, Carlos R Zanetti, Aguinaldo R Pinto
Individuals who have been exposed to human immunodeficiency virus (HIV) and have not been infected might possess natural resistance mechanisms. An understanding of the sociodemographic and immunological conditions that influence resistance to HIV is a challenge, and very little is known about the role of intrinsic antiviral factors that restrict HIV infection. The aim of this study was to analyze potential factors responsible for resistance to HIV infection in serodiscordant couples by comparing HIV-exposed seronegative individuals (HESN) to HIV-seropositive individuals treated with antiretroviral therapy (HIV-ART) along with healthy controls (HC)...
November 2015: AIDS Research and Human Retroviruses
T Leu, H-U Simon, H Hebestreit, S Kunzmann
The hypereosinophilic syndromes are rare disorders in childhood and require extensive differential diagnostic considerations. In the last years the earlier "idiopathic HES" called syndromes could be differentiated into molecular biologically, immunophenotypically and clinically more characterized heterogeneous diseases with high therapeutic and prognostic relevance. Nowadays the term HES summarizes diseases, which go hand in hand with a local or systemic hypereosinophilia (HE) connected with an organ damage...
November 2015: Klinische Pädiatrie
Xiaohong Gong, Yanyan Liu, Feng-Liang Liu, Li Jin, Hongyan Wang, Yong-Tang Zheng
Despite repeated exposures to HIV-1, some individuals remain uninfected, suggesting that genetic factors confer host resistance to HIV-1 acquisition. The chemokine receptors CCR5, CXCR4 and the principal ligand SDF1 of CXCR4 play an important role for the entry of HIV-1 to target cells. To explore the relationship between genetic variants and HIV-1 infection, 11 common SNPs in CCR5, CXCR4 and SDF1 were genotyped in 921 male intravenous drug users (IDUs), of which 263 individuals were HIV-1-exposed seropositive (HESP) and 658 were HIV-1-exposed seronegative (HESN)...
August 2015: Infection, Genetics and Evolution
Sandra Milena Gonzalez, Natalia Andrea Taborda, Manuel Gerónimo Feria, David Arcia, Wbeimar Aguilar-Jiménez, Wildeman Zapata, María Teresa Rugeles
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...
2015: PloS One
Alberto C Guardo, Marta Ruiz-Riol, Emma Fernández, Maria J Maleno, Manel E Bargalló, Agathe León, Nuria Climent, Felipe García, Jose M Gatell, Christian Brander, Montserrat Plana
BACKGROUND: Although virus-specific responses are rarely detected by conventional approaches, we report here the detection of T-cell responses in HIV-exposed seronegative (HESN) patients by two distinct assays. METHODS: HIV-specific T-cell responses were analyzed by enzyme-linked immunospot in peripheral blood mononuclear cells from HESN patients after a 48-h co-culture with boosted dendritic cells. Additionally, a boosted flow cytometry approach was used to capture antiviral T-cell responses...
July 17, 2015: AIDS
Kenzie D M Birse, Amy L Cole, Taha Hirbod, Lyle McKinnon, Terry B Ball, Garrett R Westmacott, Joshua Kimani, Frank Plummer, Alexander M Cole, Adam Burgener, Kristina Broliden
OBJECTIVE: Cationic proteins found in cervicovaginal secretions (CVS) are known to contribute to the early antiviral immune response against HIV-infection in vitro. We here aimed to define additional antiviral factors that are over-expressed in CVS from female sex workers at high risk of infection. METHODS: CVS were collected from Kenyan HIV-seronegative (n = 34) and HIV-seropositive (n = 12) female sex workers, and were compared with those from HIV-seronegative low-risk women (n = 12)...
2015: PloS One
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