Coronavirus (CoV) infections are commonly associated with respiratory and enteric disease in humans and animals. In 2012, a new human disease called Middle East respiratory syndrome (MERS) emerged in the Middle East. MERS was caused by a virus that was originally called human coronavirus-Erasmus Medical Center/2012 but was later renamed as Middle East respiratory syndrome coronavirus (MERS-CoV). MERS-CoV causes high fever, cough, acute respiratory tract infection, and multiorgan dysfunction that may eventually lead to the death of the infected individuals. The exact origin of MERS-CoV remains unknown, but the transmission pattern and evidence from virological studies suggest that dromedary camels are the major reservoir host, from which human infections may sporadically occur through the zoonotic transmission. Human to human transmission also occurs in healthcare facilities and communities. Recent studies on Middle Eastern respiratory continue to highlight the need for further understanding the virus-host interactions that govern disease severity and infection outcome. In this review, we have highlighted the major mechanisms of immune evasion strategies of MERS-CoV. We have demonstrated that M, 4a, 4b proteins and Plppro of MERS-CoV inhibit the type I interferon (IFN) and nuclear factor-κB signaling pathways and therefore facilitate innate immune evasion. In addition, nonstructural protein 4a (NSP4a), NSP4b, and NSP15 inhibit double-stranded RNA sensors. Therefore, the mentioned proteins limit early induction of IFN and cause rapid apoptosis of macrophages. MERS-CoV strongly inhibits the activation of T cells with downregulation of antigen presentation. In addition, uncontrolled secretion of interferon ɣ-induced protein 10 and monocyte chemoattractant protein-1 can suppress proliferation of human myeloid progenitor cells.

Hepatocellular carcinoma (HCC) is the fifth most common cancer, and hepatitis C virus (HCV) infection plays a major role in HCC development. The molecular mechanisms by which HCV infection leads to HCC are varied. HCV core protein is an important risk factor in HCV-associated liver pathogenesis and can modulate several signaling pathways involved in cell cycle regulation, cell growth promotion, cell proliferation, apoptosis, oxidative stress and lipid metabolism. The dysregulation of signaling pathways such as transforming growth factor β (TGF-β), vascular endothelial growth factor (VEGF), Wnt/β-catenin (WNT), cyclooxygenase-2 (COX-2) and peroxisome proliferator-activated receptor α (PPARα) by HCV core protein is implicated in the development of HCC. Therefore, it has been suggested that this protein be considered a favorable target for further studies in the development of HCC. In addition, considering the axial role of these signaling pathways in HCC, they are considered druggable targets for cancer therapy. Therefore, using strategies to limit the dysregulation effects of core protein on these signaling pathways seems necessary to prevent HCV-related HCC.

The innate immune system is the first line of defence against viral infection and characterized by production of type I interferons (IFN-α and β). 1 Antiviral response relies on pattern-recognition receptors (PRRs) of the innate immune system which recognize pathogen-associated molecular patterns (PAMPs). 2 The response is initiated by cytoplasmic protein sensors such as RIG-I (retinoic acid-inducible gene I), melanoma differentiation-associated protein 5 (MDA5) and membrane sensors as toll-like receptors (TLR3, 7, 8 and 9). 3 Type I IFNs induce the activation of signal transducer and activator of transcription (STAT) factors that induce the expression of hundreds of IFN-stimulated genes (ISGs) which act as antiviral effectors to control viral replication and spread. 4 Many viruses encode proteins that antagonize both the innate and adapted arms of the immune response. 5 All CoVs encode at least one papain-like protease (PLpro) with deubiquitinating (DUB), deISGylating (deISG) and other activities that elicit the appropriate innate immune response. 6 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) recently entered the human population at the end of 2019 from Hunnan seafood market in Wuhan, China. 7 The virus causes a pandemic infection in more than 119 million people with a case fatality ratio (CFR) of 1.4% with substantially higher ratios in older age groups, 0.32% in those aged <60 years, 6.4% in those aged ≥60 years and up to 13.4% in those aged 80 years or older. 8,9 This raises an urgent need to develop an effective treatment based on identifying targets for viral factors which blocked or reduced innate immune responses. A majority of the newly reported studies showed that PLpro,

Nuclear factor‐κB (NF‐κB), a family of master regulated dimeric transcription factors, signaling transduction pathways are active players in the cell signaling that control vital cellular processes, including cell growth, proliferation, differentiation, apoptosis, morphogenesis, angiogenesis, and immune responses. Nevertheless, aberrant regulation of the NF‐κB signaling pathways has been associated with a significant number of human cancers. In fact, NF‐κB acts as a double‐edged sword in the vital cellular processes and carcinogenesis. This review provides an overview on the modulation of the NF‐κB signaling pathways by proteins of hepatitis B and C viruses. One of the major NF‐κB events that are modulated by these viruses is the induction of hepatocellular carcinoma. Given the central function of NF‐κB in carcinogenesis, it has turned out to be a considerable therapeutic target for cancer therapy.