Flavivirus E Protein and NS2B Protein Function Quiz

Flavivirus and Togavirus: Key Molecular Features and Entry Mechanisms

• Flavivirus E protein is a type I membrane protein found as a dimer, with domain II forming a dimer interface and domain III used for receptor binding.
• Synthesis of non-structural protein results in the establishment of active RNA replicase complexes, with RNA synthesis carried out on membranes in the cytoplasm.
• Flaviviruses do not have a clearly identified cellular receptor, and entry is mediated by endocytosis within clathrin-coated vesicles.
• Antibody-dependent enhancement (ADE) can cause more severe disease like dengue hemorrhagic fever, leading to shock, organ failure, and death if not treated.
• Once the genome is in the cytosol, the RNA is bound by ribosomes and translated, producing polyprotein cleaved to produce precursor/functional protein.
• The precursor membrane protein (prM) associates with E protein in the endoplasmic reticulum to form a heterodimer, protecting E from premature conformational change.
• Togaviruses cause diseases in animals and humans, with symptoms ranging from rashes, high fever to joint pain and encephalitis.
• Togaviruses are spherical enveloped particles with a fringe of projections, and the envelope contains 240 heterodimers of glycoproteins E1 and E2, while the capsid contains 240 copies of capsid proteins.
• The Togavirus genome is a linear '+’ sense ssRNA genome, approximately 9.7-11.8kb in size, with both 5’ methylated cap and a 3’ poly(A) tail.
• The E glycoprotein of Togaviruses binds to cellular receptors, leading to receptor-mediated endocytosis via clathrin-coated vesicles.
• Once inside the cytoplasm, the RNA genome is released to be translated, and non-structural proteins catalyze the synthesis of full-length antigenome RNA.
• The RNA polymerase of Togaviruses, comprising nsP1, nsP2, and nsP4, catalyzes the synthesis of full-length antigenome RNA.

Viral Replication and Translation Processes in Picornaviruses and Flaviviruses

• Picornaviruses use cap-dependent translation mechanism, but infection causes proteolytic cleavage of eIF-4G, hindering host cell translation
• Picornaviruses hijack cellular translation by binding host cell proteins to internal ribosome entry site (IRES)
• Picornavirus proteins are made as a single precursor polyprotein, autocatalytically cleaved into capsid proteins and non-structural proteins
• Replication of picornavirus RNAs occurs in a multiprotein complex bound to cellular vesicles, utilizing negative RNA strand as a template for positive-strand synthesis
• Entry of poliovirus RNA into the cytoplasm involves major conformation changes, leading to virion assembly through cleavage of VP0 to VP2 plus VP4
• Picornavirus infection inhibits host cell functions and leads to the release of newly synthesized virions from the cell
• Flaviviruses are transmitted by arthropods and cause important human diseases, with distinct genome organization resembling Picornaviruses
• The flavivirus virion contains an envelope and 180 copies of M and E (envelope protein heterodimers) arranged with icosahedral symmetry
• Flaviviruses have a linear '+' sense ssRNA genome capped at the 5' end, translated into a single long polyprotein undergoing proteolytic processing
• Flavivirus genome organization is distinct from Togaviruses, despite similar virion morphology and transmission via arthropods
• Flavivirus RNA structures at the 3' end are cleaved into non-structural and structural proteins, including capsid, prM, M, and NS3 proteins
• NS3 protein of Flaviviruses is involved in polyprotein cleavage, RNA replication, and possesses nucleoside triphosphate and helicase activities