Genome polyprotein Antibody

The Genome polyprotein Antibody targets a protein that plays a multifaceted role in the life cycle of the virus. It participates in viral budding by interacting with the host cell membrane, encapsulating viral RNA into a nucleocapsid that forms the virus core. During entry, it may induce genome penetration into the host cytoplasm following hemifusion triggered by surface proteins. It can migrate to the nucleus where it modulates host functions. Additionally, it inhibits RNA silencing by interfering with host Dicer. The antibody also prevents premature fusion activity of envelope proteins in the trans-Golgi network by binding to envelope protein E at pH 6.0. Following virion release into the extracellular space, it dissociates from E dimers. The antibody plays a role in host immune defense modulation and protection of envelope protein E during virion synthesis. While PrM-E cleavage is often inefficient, resulting in partially matured virions with immature prM-E proteins, these proteins may contribute to immune evasion. The protein is also implicated in fetal microcephaly in humans. It acts as a chaperone for envelope protein E during intracellular virion assembly by masking and inactivating its fusion peptide. PrM is uniquely matured by host furin in the trans-Golgi network, likely to prevent premature activation of viral fusion activity in the acidic Golgi compartment before virion release. It may also play a role in virus budding. The antibody exerts cytotoxic effects by activating a mitochondrial apoptotic pathway through its M ectodomain. It may also exhibit viroporin activity. It binds to host cell surface receptors and mediates fusion between viral and cellular membranes. Efficient virus attachment to cells is, at least in part, mediated by host HAVCR1 in a cell-type specific manner. Additionally, host NCAM1 can also serve as an entry receptor. Interaction with host HSPA5 plays a crucial role in the early stages of infection. The envelope protein is synthesized in the endoplasmic reticulum and forms a heterodimer with protein prM. This heterodimer plays a role in virion budding in the ER, and the newly formed immature particle is covered with 60 spikes composed of heterodimers between precursor prM and envelope protein E. The virion is transported to the Golgi apparatus where the low pH causes the dissociation of PrM-E heterodimers and formation of E homodimers. PrM-E cleavage is often inefficient, resulting in partially matured virions with immature prM-E proteins, which may contribute to immune evasion. The antibody plays a role in the inhibition of host RLR-induced interferon-beta activation by targeting TANK-binding kinase 1/TBK1. Furthermore, it recruits the host deubiquitinase USP8 to cleave 'Lys-11'-linked polyubiquitin chains from caspase-1/CASP1, thus inhibiting its proteasomal degradation. In turn, stabilized CASP1 promotes cleavage of cGAS, which inhibits its ability to recognize mitochondrial DNA release and initiate type I interferon signaling. It is a component of the viral RNA replication complex that recruits genomic RNA, the structural protein prM/E complex, and the NS2B/NS3 protease complex to the virion assembly site, orchestrating virus morphogenesis. It also antagonizes the host MDA5-mediated induction of alpha/beta interferon antiviral response. It may disrupt adherens junction formation, impairing proliferation of radial cells in the host cortex. It is a required cofactor for the serine protease function of NS3. It displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS2B, performs its autocleavage and cleaves the polyprotein at dibasic sites in the cytoplasm: C-prM, NS2A-NS2B, NS2B-NS3, NS3-NS4A, NS4A-2K and NS4B-NS5. NS3 RNA helicase binds RNA and unwinds dsRNA in the 3' to 5' direction. It leads to translation arrest when expressed ex vivo. It regulates the ATPase activity of the NS3 helicase activity. NS4A allows NS3 helicase to conserve energy during unwinding. Cooperatively with NS4B, it suppresses the Akt-mTOR pathway, leading to cellular dysregulation. By inhibiting host ANKLE2 functions, it may cause defects in brain development, such as microcephaly. It also antagonizes the host MDA5-mediated induction of alpha/beta interferon antiviral response. It leads to translation arrest when expressed ex vivo. It functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter. It induces the formation of ER-derived membrane vesicles where viral replication takes place. It also plays a role in the inhibition of host RLR-induced interferon-beta production at TANK-binding kinase 1/TBK1 level. Cooperatively with NS4A, it suppresses the Akt-mTOR pathway, leading to cellular dysregulation. It replicates the viral (+) and (-) RNA genome, and performs the capping of genomes in the cytoplasm. It methylates viral RNA cap at guanine N-7 and ribose 2'-O positions. Once sufficient NS5 is expressed, it binds to the cap-proximal structure and inhibits further translation of the viral genome. Besides its role in RNA genome replication, it also prevents the establishment of a cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) signaling pathway. Mechanistically, it interferes with host kinases TBK1 and IKKE upstream of interferon regulatory factor 3/IRF3 to inhibit the RIG-I pathway. It also antagonizes type I interferon signaling by targeting STAT2 for degradation by the proteasome, thereby preventing activation of JAK-STAT signaling pathway. Within the host nucleus, it disrupts host SUMO1 and STAT2 co-localization with PML, resulting in PML degradation. It may also reduce immune responses by preventing the recruitment of the host PAF1 complex to interferon-responsive genes.