accessory protein ORF4b, also known as non-structural protein 3c (NS3c), of betacoronaviruses in the C lineageThis model represents the accessory protein 4b, ORF4b (also called NS3c protein) of Middle East respiratory syndrome (MERS)-related CoV and similar proteins from betacoronaviruses in the merbecovirus subgenera (C lineage), including Tylonycteris bat coronavirus HKU4 and Pipistrellus bat coronavirus HKU5. There are five essential genes in CoVs that result in the following gene products: Spike (S) protein, Membrane (M) glycoprotein, Nucleocapsid (N), Envelope (E) protein, and replicase/protease polyproteins (ORF1ab); all are required to produce a structurally complete viral particle. In addition, CoV genomes also contain ORFs coding for accessory proteins that are specific for certain CoV lineages or for a particular CoV. In general, CoV accessory proteins are considered to be dispensable for viral replication, however several accessory proteins have been shown to exhibit functions in virus-host interactions during CoV infection. ORF4b/NS3c plays a role in the inhibition of host innate immunity by inhibiting the interaction between host IkappaB kinase epsilion (IKBKE or IKKE) and mitochondrial antiviral-signalling protein (MAVS). In turn, this inhibition prevents the production of host interferon beta. Additionally, it may also interfere with host antiviral response within the nucleus. The MERS-CoV ORF4b (also known as MERS-CoV 4b) has been shown to interfere with the NF-kappaB-dependent innate immune response during infection, as well as antagonizing the early antiviral alpha/beta interferon (IFN-alpha/beta) response, which may significantly contribute to MERS-CoV pathogenesis.