lecular patterns (PAMPs) and signal through TLR2 and itsheterodimers leading to significantly increased HIV infec-tion,NFjB-dependent activation and proinflammatory cytokineproduction. These findings have important implications for ourunderstanding of HIV immune activation, pathogenesis andvaccine development.

P12.14Phenotypic Characterization of Natural Killer (NK)Cells in Antiretroviral Naıve Chronically InfectedHIV-1 Patients (the CIRCB Afrodec Cohort)

Carole Stephanie Sake Ngane1,2, Jules C. Tchadji1,3, AchilleNangue1, Nadesh Nji1, Georgia Ambada1,3, Edith Temgoua1,Samuel Sosso1, Rachel Kamgaing1, Francois-Xavier Etoa2,Godwin Nchinda1

11-CIRCB/Microbiology and Immunology Lab, Yaounde,Cameroon, 2University of Yaounde I, Department of Biochem-istry, Yaounde, Cameroon, 3University of Yaounde I, Yaounde,Cameroon

Background: Natural Killer (NK) cells are effectors cells of theinnate immune system which play a critical role as a first line ofdefense against viral infection. They are characterized as CD3-CD56 + CD16 + / - cells and effect cytotoxic activity againsttarget cells as well as cytokines and chemokines production. NKcytotoxicity is modulated by inhibitory and activating receptors.HIV-1 infection maintains immune system in a sustained state ofactivation and causes immune dysfunction. However the impactof NK cell phenotype modulation has not been acessed in thecontext of Antiretroviral naıve HIV-1 infection.We shall verify the existence of HIV-specific NK cells in anti-retroviral naıve chronically infected HIV-1 patients.Methods: 35 treatment naıve HIV-1 patients, CD4 greater than350 cell/ll and 30 healthy donors were recruited. Age rangedfrom 21 to 65 years old. Patients group was composed of 5patients with Viral load (VL) < 2Log, 23 VL between 2-4, 5 Logand 07 VL > 4,5 Log. PBMCs were obtained from whole bloodusing ficoll-paque density grandient. NK cells are analyzed bymultiparametric flow cytometry in bulk PBMCs. samples wereaquired using BD FACScanto II machine and data analysed byflowjo 7.4Results: There was a differential modulation of NK cell pheno-type as we observed a decreased expression of activating markersNKP30, NKP44, NKP46 and a significant increase (P < 0,05) in theexpression of HLADR, CD38 and NKG2D in treatment naıveHIV-1 infected patients relative to healthy donors. Down regula-tion of NKG2A expression was also observed in the patients group.Conclusions: This study shows phenotypic pertubations on NKcells in treatment naive HIV-1 infected patients. Observation ofincreased expression of activating receptors NKG2D, CD38 andHLA-DR is a pathological signature of HIV-1 infection howevera decreased NKG2A in expression could be necessary in in-crease cytolytic function of NK cells.

P12.15Human Beta Defensins and RNases: Antiviral Effectduring Sexual Exposure to HIV-1

Wildeman Zapata1,2, Wbeimar Aguilar-Jimenez1, Zhimin Feng3,Aaron Weinberg3, Aniello Russo4, Nicoletta Potenza4, Her-nando Estrada5, Maria Teresa Rugeles1

1Universidad de Antioquia UdeA, Facultad de Medicina, GrupoInmunovirologıa, Medellin, Colombia, 2Universidad Co-operativa de Colombia, Facultad de Medicina, Grupo Infettare,Medellin, Colombia, 3Case Western Reserve University, Schoolof Dental Medicine, Department of Biological Sciences, Cle-veland, OH, United States, 4Second University of Naples, De-partment of Life Sciences, Naples, Italy, 5HERES Health,Lending Institution of Health, Santa Marta, Colombia

Background: Individuals demonstrating natural resistance toHIV infection, despite repeated unprotected sexual exposure, arereferred to as HIV-1-exposed seronegative (HESN), and areconsidered a model to determine mechanisms of protection. In-nate immune factors, such as human beta defensins (HBD), andRNases, previously known for their antiviral potential, are presentat mucosal barriers, main ports of HIV entry, suggesting theirinvolvement in avoiding the establishment of HIV infection.Methods: To evaluate the role of these factors in the naturalresistance to HIV-1, we performed a study, including 60 HESN,and 61 healthy controls (HC). Vaginal, endocervical and oralmucosal samples were taken from these individuals; RNA wasextracted, and mRNA transcripts of HBD-2, -3, and the Ribo-nucleases, eosinophil-derived neurotoxin (EDN), RNase-1 andangiogenin were quantified by qPCR. In addition, we exploredthe step(s) of the viral cycle that was inhibited by these solublefactors, using an in vitro single-round, recombinant-based, viralinfectivity assay.Results: Oral mucosa of HESN expressed significantly higherlevels of hBD-2 ( p = 0.04) and hBD-3 ( p = 0.04) mRNA comparedto HC. Likewise, vaginal mucosa of HESN showed significantlyhigher mRNA levels of RNase-1 compared to HC ( p = 0.036); inaddition, endocervical mucosa showed higher mRNA levels ofEDN ( p = 0.04) and Angiogenin ( p = 0.02) compared to HC. Fi-nally, HBDs and RNases inhibited HIV-1 replication, in a dosedependent manner at the following steps of the viral replicationcycle: entry, reverse transcription and nuclear import.Conclusions: Taken together, these results suggest that innateimmune factors, such as HBD-2 and -3, and RNases inhibitHIV-1 infection during either oral or genital exposure of HIV. Infact, HBDs and RNases inhibited in vitro replication of HIV-1,pointing their potential role as antiretroviral molecules to beexplored in the near future.

P12.16Sex Differences in TNFAIP3 Levels in pDCupon TLR7 Stimulation

Susanne M. Ziegler1, Morgane Griesbeck2,3, Judy Chang4,Marcus Altfeld1,2

1Heinrich Pette Institute, Leibniz Institute for ExperimentalVirology, Viral Immunology, Hamburg, Germany, 2Ragon In-stitute of MIT, MGH and Harvard, Boston, MA, United States,3CIMI/ U1135, Paris, France, 4Monash University, Departmentof Infectious Diseases, Melbourne, Australia

Background: The outcomes of many diseases differ betweenwomen and men. It is well documented that women have ahigher incidence as well as more severe pathogenesis of auto-immune diseases. Furthermore, accumulating evidence indicatesa role of sex-based divergence of infectious diseases, includinginfluenza and HIV-1. In HIV-1 infection, clinical studies haveshown faster disease progression and stronger immune activa-tion in females compared to males for the same level of viral

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