The Interplay between Host Innate Immunity and Hepatitis E Virus

Abstract

Hepatitis E virus (HEV) infection represents an emerging global health issue, whereas the clinical outcomes vary dramatically among different populations. The host innate immune system provides a first-line defense against the infection, but dysregulation may partially contribute to severe pathogenesis. A growing body of evidence has indicated the active response of the host innate immunity to HEV infection both in experimental models and in patients. In turn, HEV has developed sophisticated strategies to counteract the host immune system. In this review, we aim to comprehensively decipher the processes of pathogen recognition, interferon, and inflammatory responses, and the involvement of innate immune cells in HEV infection. We further discuss their implications in understanding the pathogenic mechanisms and developing antiviral therapies.

Modulation of the Innate Immune Response by Targeting Toll-like Receptors: A Perspective on Their Agonists and Antagonists

“…This feature enables this PRR to trigger innate immune response against dsRNA viruses, such as rotavirus, but also ssRNA viruses, e.g., Hantaan virus (HV), RSV, West Nile Virus (WNV), coxsackievirus B3 (CVB3), IAV, Punta Toro Virus (PTV), HCV, HEV, Dengue Virus (DENV), encephalomyocarditis virus (EMCV), and poliovirus. Moreover, even some DNA viruses, such as EBV, VV, Kaposi’s sarcoma-associated herpesvirus (KSHV), HBV, HSV-1, and HSV-2, can be recognized by TLR3. ,,− Interestingly, TLR3 is heavily involved in several viral infections of the central nervous system (CNS), where it can play either a protective or detrimental role for the host. Indeed, TLR3 has been related to the immune response against Japanese encephalitis virus (JEV), tick-borne encephalitis virus (TBEV), enterovirus-A71 (EV-A71), and Zika virus (ZIKV); sometimes, it also plays a role in the excessive neuro-inflammation that let rabies virus (RABV) or WNV invade neurons. , Also, other viruses can take advantage of the TLR3 signaling activation, resulting either in lower host resistance to lethal infections, as it happens for PTV, or in a detrimental inflammatory response, as it happens for IAV and VV in the lungs .…”

Inhibition of Antiviral Innate Immunity by Avibirnavirus VP3 via Blocking TBK1-TRAF3 Complex Formation and IRF3 Activation

“…IFN-β is one of the major cytokines rapidly triggered by many viruses in infected cells and plays a critical role in the innate antiviral response ( 8 ). To combat the antiviral effects of IFN-β, many viruses, including Avibirnavirus , have evolved various elaborate mechanisms to subvert host innate immunity ( 9 – 11 ). Infectious bursal disease virus (IBDV), the representative member of the genus Avibirnavirus in the family Birnaviridae , contains a double-stranded RNA (dsRNA) genome comprising segments A and B and encodes RNA-dependent RNA polymerase VP1, two structural proteins (VP2 and VP3), a viral protease (VP4), and a nonstructural protein (VP5) ( 12 – 14 ).…”

Hepatitis E Virus: How It Escapes Host Innate Immunity

“…This review summarizes what is presently known of the immune response to HEV, and how the various virus proteins are implicated in immune evasion. The innate immune cell response is not addressed, since it has been recently [ 41 ].…”