Hepatitis C virus NS5A targets the nucleosome assembly protein NAP1L1 to control the innate cellular response

Hepatitis C virus (HCV) is a single-stranded positive-sense RNA hepatotropic virus. Despite cellular defenses, HCV is able to replicate in hepatocytes and to establish a chronic infection that could lead to severe complications and hepatocellular carcinoma. An important player in subverting the host response to HCV infection is the viral non-structural protein NS5A that, in addition to its role in replication and assembly, targets several pathways involved in the cellular response to viral infection. Several unbiased screens identified the nucleosome-assembly protein 1-like 1 (NAP1L1) as an interaction partner of HCV NS5A. Here we confirm this interaction and map it to the C-terminus of NS5A of both genotype 1 and 2. NS5A sequesters NAP1L1 in the cytoplasm blocking its nuclear translocation. However, only NS5A from genotype 2 HCV, but not from genotype 1, targets NAP1L1 for proteosomal-mediated degradation. NAP1L1 is a nuclear chaperone involved in chromatin remodeling and we demonstrate the NAP1L1-dependent regulation of specific pathways involved in cellular responses to viral infection and cell survival. Among those we show that lack of NAP1L1 leads to a decrease of RELA protein levels and a strong defect of IRF3 TBK1/IKKϵ-mediated phosphorylation leading to inefficient RIG-I and TLR3 responses. Hence, HCV is able to modulate the host cell environment by targeting NAP1L1 through NS5A

İNME KLİNİK PRATİĞİNDE NOAK KULLANIMI:TÜRK BEYİN DAMAR HASTALIKLARI DERNEĞİ UZMAN GÖRÜŞÜ

Non-vitamin K oral antikoagülanların (NOAK) atrial fibrilasyonda inmenin önlenmesi amacıyla on yılı aşan bir süredirbaşarı ile kullanıldığı açıktır. Varfarine göre belirgin derecede az kanamaya yol açmaları ve inmeyi de eşit veya daha fazlaoranda önleyebilmeleri yanı sıra kolay kullanım özellikleri primer proflakside atrial fibrilasyona bağlı inmeyi azaltmakonusunda öne çıkmaktadır. Bunlar aynı zamanda genel inme prevalansının azalması anlamına gelmektedir. Yani AFnedenli inmenin engellenmesi toplum sağlığı için çağdaş bir gereklilik olarak algılanmalıdır. İnme klinik pratiğindekardiyoloji uzmanları ile birlikte bu bağlamda çaba sarf eden nöroloji uzmanları için Türk Beyin Damar HastalıklarıDerneği bu uzman görüşünü hazırladı. Görüşler NOAK grubu ilaçların kullanımında sıkça karşılaşılan sorunlar ve buproblemler için güncel çözüm önerilerini içermektedir.It is clear that nonvitamin K oral anticoagulants (NOACs) have been used successfully for more than ten years to preventstroke in atrial fibrillation. In addition to the fact that they cause significantly less bleeding compared to warfarin and canprevent stroke equally or more, their easy-to-use features stand out in reducing stroke due to atrial fibrillation in primaryprophylaxis. These also mean a decrease in the overall prevalence of stroke. For sure, prevention of AF-induced strokeshould be perceived as a contemporary requirement for public health. Turkish Society of Cerebrovascular Diseases hasprepared this expert opinion for neurologists who strive for this purpose together with cardiologists in the clinicalpractice of stroke. The article contains frequently encountered problems in the use of NOACs and current solutions forthese problems