The correlation of neutralizing antibodies to treatment outcome in patients with chronic hepatitis C virus (HCV) infection is not established. HCV genotype 1 cell culture recombinants (1a: H77/JFH1 TN/JFH1 DH6/JFH1; 1b: J4/JFH1 DH1/JFH1 DH5/JFH1). The results were expressed as the highest dilution yielding 50% neutralization (NAb50-titer). We observed no genotype or subtype specific differences in NAb50-titers between patients with chronic HCV infection with and without sustained virologic response when tested against any of the included culture viruses. However NAb50-titers varied significantly with a mean reciprocal NAb50-titer of 800 (range: 100-6400) against DH6/JFH1 compared to a mean NAb50-titer of 50 (range: <50-400) against all other included isolates. Subsequent studies demonstrated that the efficient neutralization of DH6/JFH1 could be linked to engineered adaptive mutations in the envelope-2 protein. In analysis of envelope 1 and 2 sequences of HCV recovered from a subset of patients we observed no apparent link between relatedness of patient sequences with culture viruses used and the corresponding neutralization results. In conclusion pre-treatment levels of neutralizing antibodies against HCV genotype 1 isolates could not predict treatment outcome in patients with chronic LY315920 HCV infection. High neutralization susceptibility of DH6/JFH1 could be correlated with adaptive envelope mutations previously highlighted as important for neutralization. Our study emphasizes the importance of using multiple culture viruses for neutralization studies and contributes to the current knowledge about neutralizing LY315920 epitopes important for future therapeutic- and vaccine-studies. Introduction Hepatitis C virus (HCV) is a human pathogen infecting approximately 170 million LY315920 people worldwide hereby increasing the risk of developing serious chronic liver diseases including liver cirrhosis and hepatocellular carcinoma (HCC) [1]. The standard of care treatment for HCV genotype 1 infected patients has for the last decade been a combination therapy of pegylated interferon-α and ribavirin (PEGIFN/RBV) for 48 weeks [2]. The effect of this treatment regimen is monitored by measuring the HCV RNA levels in serial blood samples. Only about 50% of the treated patients achieve a Sustained Virologic Response (SVR) defined as undetectable HCV RNA 24 weeks post treatment termination. Early Virologic Response (EVR) is defined as negative or ≥2 log10 decrease in HCV RNA 12 weeks after treatment initiation. Sufferers with EVR will attain SVR while sufferers without EVR possess a significant decreased potential for SVR and for that reason will terminate treatment at PLD1 this time of your time [3]. In 2011 two guaranteeing NS3/4A protease inhibitors had been released as an add-on towards the PEGIFN/RBV treatment enhancing the response price to around 70% [4]-[6]. Sadly the 3-medication therapy also escalates the amount of adverse occasions and severe epidermis reactions like Medication LY315920 Response with Eosinophilia and Systemic Symptoms (Outfit) and Steven Johnson symptoms have already been reported [4] [7]. This means that the continued dependence on predictive factors allowing clinicians LY315920 to judge the probably treatment outcome for their patients. Several host- viral- and therapeutic- factors have been reported as predictors of outcome of combination treatment with PEGIFN/RBV [2] [8]-[11]. As impartial factors genotype baseline viral load age at treatment initiation IL28β genotype IP-10 level and duration of treatment have consistently been found to be strong predictors [2] [9] [12]. A LY315920 systematic approach regarding possible predictive factors in relation to the viral life cycle has until recently been hampered by the lack of robust cell-culture systems. However in 2005 a cell-culture system based on HCV strain JFH1 from a Japanese patient was developed [13]. The subsequent development of JFH1-based virus systems expressing strain specific envelope proteins permitted cross genotype neutralization studies [14]-[21]. These systems function as important tools studying the complete viral life cycle and factors with influence on virus fitness like neutralizing antibodies and host cell factors. Various studies have shown that a broad and vigorous cellular immune response is needed to clear the virus in the acute phase [22] [23] where the role of NAb is usually less clear [24]-[27]. In the chronic contamination defined as HCV viremia persistence more than 6 months the virus persists despite HCV specific T-cell responses. In most of these patients high levels of NAb can be detected..