Hajar Chihab1, Imane Zaidane2, Abdellah Elhabazi3, Fatima-Zahra Jadid2, Raouia El Fihri2, Mohcine Elmessaoudi-Idrissi2, Mohammed Chair3, Wafaa Badre4, Mohamed Tahiri4, Pascal Pineau5, Isabelle Chemin6, Sayeh Ezzikouri2, Soumaya Benjelloun7. 1. Virology Unit, Viral Hepatitis Laboratory, Institut Pasteur du Maroc, Casablanca, Morocco; Laboratoire de Biotechnologie, Biochimie et Nutrition - Université Chouaib Doukkali, Faculté des Sciences d'El Jadida, 24000 El Jadida, Morocco. 2. Virology Unit, Viral Hepatitis Laboratory, Institut Pasteur du Maroc, Casablanca, Morocco. 3. Laboratoire de Biotechnologie, Biochimie et Nutrition - Université Chouaib Doukkali, Faculté des Sciences d'El Jadida, 24000 El Jadida, Morocco. 4. Faculté de médecine de Casablanca, CHU Ibn Rochd, Casablanca, Morocco. 5. Unité "Organisation Nucléaire et Oncogenèse", INSERM U993, Institut Pasteur, Paris, France. 6. INSERM U1052, CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon Université Claude Bernard, Lyon, France. 7. Virology Unit, Viral Hepatitis Laboratory, Institut Pasteur du Maroc, Casablanca, Morocco. Electronic address: soumaya.benjelloun@pasteur.ma.
Abstract
OBJECTIVES: Toll-like receptor 9 (TLR9) plays a crucial role in the innate immune response against viral infections. The failure of this system may result, in an attenuated immune response against HBV. Recent research has focused on the possibility of targeting the defects in TLR9 pathway as a novel approach for anti-HBV treatment. Our study aimed to assess the impact of both TLR9 rs5743836 and rs187084 polymorphisms on spontaneous HBV clearance in Moroccan chronic HBV carriers. METHODS: In this study, 239 individuals chronically infected with HBV (CHB) and 133 subjects who spontaneously resolved the infection (SRB) were genotyped using a Taqman allelic discrimination assay. RESULTS/ CONCLUSION: Remarkably, we observed a dosage effect of both SNPs on viral loads; with a significant increase of circulating HBV DNA within AA, AG to GG rs5743836 genotypes, whereas the inverse phenomenon was noticed within rs187084 genotypes. There were no consistent association between TLR9 polymorphisms and spontaneous clearance of HBV, however, a significant association was observed between rs187084 AA genotype and HBV progression to advanced liver disease. Further studies on larger populations might be necessary to understand the modulating effect of TLR9 polymorphisms on HBV loads that remain a viral factor of paramount importance to predict HCC development.
OBJECTIVES:Toll-like receptor 9 (TLR9) plays a crucial role in the innate immune response against viral infections. The failure of this system may result, in an attenuated immune response against HBV. Recent research has focused on the possibility of targeting the defects in TLR9 pathway as a novel approach for anti-HBV treatment. Our study aimed to assess the impact of both TLR9rs5743836 and rs187084 polymorphisms on spontaneous HBV clearance in Moroccan chronic HBV carriers. METHODS: In this study, 239 individuals chronically infected with HBV (CHB) and 133 subjects who spontaneously resolved the infection (SRB) were genotyped using a Taqman allelic discrimination assay. RESULTS/ CONCLUSION: Remarkably, we observed a dosage effect of both SNPs on viral loads; with a significant increase of circulating HBV DNA within AA, AG to GG rs5743836 genotypes, whereas the inverse phenomenon was noticed within rs187084 genotypes. There were no consistent association between TLR9 polymorphisms and spontaneous clearance of HBV, however, a significant association was observed between rs187084 AA genotype and HBV progression to advanced liver disease. Further studies on larger populations might be necessary to understand the modulating effect of TLR9 polymorphisms on HBV loads that remain a viral factor of paramount importance to predict HCC development.