Details

Autor(en) / Beteiligte

• Ríos-Ocampo, W. Alfredo
• Navas, María-Cristina
• Faber, Klaas Nico
• Daemen, Toos
• Moshage, Han

Titel

The cellular stress response in hepatitis C virus infection: A balancing act to promote viral persistence and host cell survival

Ist Teil von

• Virus research, 2019-04, Vol.263, p.1-8

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• •Despite the development of a successful antiviral treatment, there are still research challenges focused on HCV eradication, one of them is about unanswered questions of the host-virus interaction and its effects in viral persistence and liver damage.•It is well known that oxidative- and endoplasmic reticulum (ER)-stress are common events during hepatitis C virus (HCV) infection. However, to less is discuss about the adaptive response in hepatocytes to face cellular stress in the context of HCV infection.•In hepatocytes, different types of autophagy can be observed simultaneously as a result of cellular stress. Thus, the autophagy type and its role should be analyzed and discriminated as positive or negative regulator of HCV replication and persistence.•In this review, we suggest that the adaptive response to cellular stress is a key host factor in the clearance of the HCV. Then, new therapeutic options to combat HCV infection should be focused as well on enhancing the adaptive response of the host to cellular stress. Oxidative- and endoplasmic reticulum (ER)-stress are common events during hepatitis C virus (HCV) infection and both regulate cell survival and determine clinical outcome. In response to intrinsic and extrinsic cellular stress, different adaptive mechanisms have evolved in hepatocytes to restore cellular homeostasis like the anti-oxidant response, the unfolded protein response (UPR) and the integrated stress response (ISR). In this review, we focus on the cellular stress response in the context of acute and chronic HCV infection. The mechanisms of induction and modulation of oxidative- and ER-stress are reviewed and analyzed from both perspectives: viral persistence and cell survival. Besides, we delve into the activation of the eIF2α/ATF4 pathway and selective autophagy induction; pathways involved in the elimination of harmful viral proteins after oxidative stress induction. For this, the negative role of autophagy upon HCV infection or negative regulation of viral replication is analyzed. Finally, we hypothesize that the cellular stress response in hepatocytes plays a major role for HCV control thus acting as an important host-factor for virus clearance during the early stages of HCV infection.