Hepatitis C is a global public health problem, and Pakistan is the second largest country in the globe with highest prevalence rate of hepatitis C virus (HCV). Until 2014, pegylated interferon (PEG-IFN) plus ribavirin (RBV) has been the standard therapy for HCV, however, owing to its adverse side effects and very low sustained virologic response (SVR) rates therapeutics trend is shifted toward direct-acting antivirals. Tripartite motif containing 22 (TRIM22) is a dynamic antiviral protein that can inhibit multiple viruses in vivo. Expression of TRIM22 mRNA has been linked to outcome of PEG-IFN and ribavirin therapy, where its higher expression leads to rapid virus clearance. However, in terms of therapy with direct-acting antiviral (DAA) or double DAA, impact of TRIM22 expression is largely unknown. These new drugs show more than 90% of SVR rates and lesser side effects and have proven to be better than IFN therapy. Endogenous IFN system suppresses various pathogens through the induction of antiviral effectors termed as interferon-stimulating genes (ISGs). We have studied the expression levels of one of these antiviral effectors, TRIM22 in response to sofosbuvir (SOF) and daclatasvir (DAC) in combination with RBV, using quantitative PCR in the peripheral blood mononuclear cells (PBMCs) of HCV-infected patients. We have observed sustained virus clearance in more than 90% of patients treated with DAA and double DAA and have seen the expression of TRIM22 to be higher in patients who attained SVR as compared to the untreated patients. We have also observed downregulation of TRIM22 in patients who failed to attain rapid virus clearance, and upregulation in those who achieved rapid clearance of virus. Genetic factors that determine the lower TRIM22 expression in these patients are needed to be explored that may also play a role in lower response to anti-HCV therapy. Endogenous IFN system and effects of antiviral proteins in response to DAA therapy is needed to be studied in order to better understand the host response toward these drugs to make them more effective.

中文翻译：

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在直接作用抗病毒药物治疗的慢性丙型肝炎患者中TRIM22 mRNA的表达。

丙型肝炎是全球性的公共卫生问题，巴基斯坦是全球第二大丙型肝炎病毒（HCV）患病率最高的国家。直到2014年，聚乙二醇干扰素（PEG-IFN）和利巴韦林（RBV）一直是HCV的标准疗法，但是，由于其不良副作用和极低的持续病毒学应答（SVR）率，治疗趋势已转向直接作用抗病毒药。包含22的三方基序（TRIM22）是一种动态抗病毒蛋白，可以在体内抑制多种病毒。TRIM22 mRNA的表达与PEG-IFN和利巴韦林疗法的结局有关，后者的更高表达导致病毒快速清除。但是，就使用直接作用抗病毒（DAA）或双重DAA的治疗而言，TRIM22表达的影响尚不清楚。这些新药显示出超过90％的SVR率和较小的副作用，并被证明比IFN治疗更好。内源性IFN系统通过诱导被称为干扰素刺激基因（ISG）的抗病毒效应子来抑制各种病原体。我们使用定量PCR在HCV感染患者的外周血单核细胞（PBMC）中研究了其中一种抗病毒效应物TRIM22对sofosbuvir（SOF）和daclatasvir（DAC）与RBV的反应的表达水平。我们已经观察到超过90％的接受DAA和双DAA治疗的患者具有持续的病毒清除能力，并且与未治疗的患者相比，获得SVR的患者中TRIM22的表达更高。我们还观察到未能快速清除病毒的患者中TRIM22的下调，和那些迅速清除病毒的人的上调。需要探索确定这些患者中TRIM22表达较低的遗传因素，这些因素也可能在抗HCV治疗的较低应答中起作用。为了更好地了解宿主对这些药物的反应，使其更有效，需要研究内源性IFN系统和抗病毒蛋白对DAA治疗的反应。