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Interferons are a group of signaling proteins made and released by host cells in response to the presence of several viruses. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten their anti-viral defenses.
Rotavirus is a genus of double-stranded RNA viruses in the family Reoviridae. Rotaviruses are the most common cause of diarrhoeal disease among infants and young children. Nearly every child in the world is infected with a rotavirus at least once by the age of five. Immunity develops with each infection, so subsequent infections are less severe. Adults are rarely affected. There are nine species of the genus, referred to as A, B, C, D, F, G, H, I and J. Rotavirus A, the most common species, causes more than 90% of rotavirus infections in humans.
Human Herpes Virus (HHV) Infected Cell Polypeptide 0 (ICP0) is a protein, encoded by the DNA of herpes viruses. It is produced by herpes viruses during the earliest stage of infection, when the virus has recently entered the host cell; this stage is known as the immediate-early or α ("alpha") phase of viral gene expression. During these early stages of infection, ICP0 protein is synthesized and transported to the nucleus of the infected host cell. Here, ICP0 promotes transcription from viral genes, disrupts structures in the nucleus known as nuclear dots or promyelocytic leukemia (PML) nuclear bodies, and alters the expression of host and viral genes in combination with a neuron specific protein. At later stages of cellular infection, ICP0 relocates to the cell cytoplasm to be incorporated into new virion particles.
The NS1 influenza protein (NS1) is a viral nonstructural protein encoded by the NS gene segments of type A, B and C influenza viruses. Also encoded by this segment is the nuclear export protein (NEP), formally referred to as NS2 protein, which mediates the export of influenza virus ribonucleoprotein (RNP) complexes from the nucleus, where they are assembled.
Interferon regulatory factors (IRF) are proteins which regulate transcription of interferons. Interferon regulatory factors contain a conserved N-terminal region of about 120 amino acids, which folds into a structure that binds specifically to the IRF-element (IRF-E) motifs, which is located upstream of the interferon genes. Some viruses have evolved defense mechanisms that regulate and interfere with IRF functions to escape the host immune system. For instance, the remaining parts of the interferon regulatory factor sequence vary depending on the precise function of the protein. The Kaposi sarcoma herpesvirus, KSHV, is a cancer virus that encodes four different IRF-like genes; including vIRF1, which is a transforming oncoprotein that inhibits type 1 interferon activity. In addition, the expression of IRF genes is under epigenetic regulation by promoter DNA methylation.
The type-I interferons (IFN) are cytokines which play essential roles in inflammation, immunoregulation, tumor cells recognition, and T-cell responses. In the human genome, a cluster of thirteen functional IFN genes is located at the 9p21.3 cytoband over approximately 400 kb including coding genes for IFNα, IFNω (IFNW1), IFNɛ (IFNE), IFNк (IFNK) and IFNβ (IFNB1), plus 11 IFN pseudogenes.
Interferon regulatory factor 3, also known as IRF3, is an interferon regulatory factor.
NSP2 (NS35), is a rotavirus nonstructural RNA-binding protein that accumulates in cytoplasmic inclusions (viroplasms) and is required for genome replication. NSP2 is closely associated in vivo with the viral replicase. The non-structural protein NSP5 plays a role in the structure of viroplasms mediated by its interaction with NSP2.
Putative transmembrane domain more commonly known as Non-structural Protein 6 (NSP6) is one of the two non-structural proteins that gene 11 in rotavirus encodes for alongside NSP5. NSP6 is composed of six transmembrane domains and a C terminal tail. In contrast to the other rotavirus non-structural proteins, NSP6 was found to have a high rate of turnover, being completely degraded within 2 hours of synthesis. NSP6 was found to be a sequence-independent nucleic acid binding protein, with similar affinities for ssRNA and dsRNA
Interferon regulatory factor 7, also known as IRF7, is a member of the interferon regulatory factor family of transcription factors.
Interferon alpha-2 is a protein that in humans is encoded by the IFNA2 gene.
Mitochondrial antiviral-signaling protein (MAVS) is a protein that is essential for antiviral innate immunity. MAVS is located in the outer membrane of the mitochondria, peroxisomes, and mitochondrial-associated endoplasmic reticulum membrane (MAM). Upon viral infection, a group of cytosolic proteins will detect the presence of the virus and bind to MAVS, thereby activating MAVS. The activation of MAVS leads the virally infected cell to secrete cytokines. This induces an immune response which kills the host's virally infected cells, resulting in clearance of the virus.
MDA5 is a RIG-I-like receptor dsRNA helicase enzyme that is encoded by the IFIH1 gene in humans. MDA5 is part of the RIG-I-like receptor (RLR) family, which also includes RIG-I and LGP2, and functions as a pattern recognition receptor capable of detecting viruses. It is generally believed that MDA5 recognizes double stranded RNA (dsRNA) over 2000nts in length, however it has been shown that whilst MDA5 can detect and bind to cytoplasmic dsRNA, it is also activated by a high molecular weight RNA complex composed of ssRNA and dsRNA. For many viruses, effective MDA5-mediated antiviral responses are dependent on functionally active LGP2. The signaling cascades in MDA5 is initiated via CARD domain. Some observations made in cancer cells show that MDA5 also interacts with cellular RNA is able to induce an autoinflammatory response.
Tetherin, also known as bone marrow stromal antigen 2, is a lipid raft associated protein that in humans is encoded by the BST2 gene. In addition, tetherin has been designated as CD317. This protein is constitutively expressed in mature B cells, plasma cells and plasmacytoid dendritic cells, and in many other cells, it is only expressed as a response to stimuli from IFN pathway.
Nonstructural protein 5A (NS5A) is a zinc-binding and proline-rich hydrophilic phosphoprotein that plays a key role in Hepatitis C virus RNA replication. It appears to be a dimeric form without trans-membrane helices.
Interferon alpha-16, also known as IFN-alpha-16, is a protein that in humans is encoded by theIFNA16 gene.
RIG-I-like receptors are a type of intracellular pattern recognition receptor involved in the recognition of viruses by the innate immune system. RIG-I is the best characterized receptor within the RIG-I like receptor (RLR) family. Together with MDA5 and LGP2, this family of cytoplasmic pattern recognition receptors (PRRs) are sentinels for intracellular viral RNA that is a product of viral infection. The RLR receptors provide frontline defence against viral infections in most tissues.
Picornain 3C is a protease found in picornaviruses, which cleaves peptide bonds of non-terminal sequences. Picornain 3C’s endopeptidase activity is primarily responsible for the catalytic process of selectively cleaving Gln-Gly bonds in the polyprotein of poliovirus and with substitution of Glu for Gln, and Ser or Thr for Gly in other picornaviruses. Picornain 3C are cysteine proteases related by amino acid sequence to trypsin-like serine proteases. Picornain 3C is encoded by enteroviruses, rhinoviruses, aphtoviruses and cardioviruses. These genera of picoviruses cause a wide range of infections in humans and mammals.
The cGAS–STING pathway is a component of the innate immune system that functions to detect the presence of cytosolic DNA and, in response, trigger expression of inflammatory genes that can lead to senescence or to the activation of defense mechanisms. DNA is normally found in the nucleus of the cell. Localization of DNA to the cytosol is associated with tumorigenesis, viral infection, and invasion by some intracellular bacteria. The cGAS – STING pathway acts to detect cytosolic DNA and induce an immune response.
Bunyaviridae nonstructural S proteins (NSs) are synthesized by viral DNA/RNA and do not play a role in the replication or the viral protein coating. The nonstructural S segment (NSs) created by Bunyaviridae virus family, are able to interact with the human immune system, in order to increase their replication in infected cells. Understanding this mechanism can have global health impacts.
References
- ↑ Hua J, Mansell EA, Patton JT (September 1993). "Comparative analysis of the rotavirus NS53 gene: conservation of basic and cysteine-rich regions in the protein and possible stem-loop structures in the RNA". Virology. 196 (1): 372–8. doi: 10.1006/viro.1993.1492 . PMID 8395125.
- ↑ Hua J, Patton JT (February 1994). "The carboxyl-half of the rotavirus nonstructural protein NS53 (NSP1) is not required for virus replication". Virology. 198 (2): 567–76. doi: 10.1006/viro.1994.1068 . PMID 8291239.
- ↑ Dunn SJ, Cross TL, Greenberg HB (August 1994). "Comparison of the rotavirus nonstructural protein NSP1 (NS53) from different species by sequence analysis and northern blot hybridization". Virology. 203 (1): 178–83. doi: 10.1006/viro.1994.1471 . PMID 8030275.
- ↑ Okada J, Kobayashi N, Taniguchi K, Urasawa S (1999). "Analysis on reassortment of rotavirus NSP1 genes lacking coding region for cysteine-rich zinc finger motif". Archives of Virology. 144 (2): 345–53. doi:10.1007/s007050050508. PMID 10470258. S2CID 13288814.
- ↑ Barro M, Patton JT (March 2005). "Rotavirus nonstructural protein 1 subverts innate immune response by inducing degradation of IFN regulatory factor 3". Proceedings of the National Academy of Sciences of the United States of America. 102 (11): 4114–9. Bibcode:2005PNAS..102.4114B. doi: 10.1073/pnas.0408376102 . PMC 554789 . PMID 15741273.
- ↑ Graff JW, Ewen J, Ettayebi K, Hardy ME (February 2007). "Zinc-binding domain of rotavirus NSP1 is required for proteasome-dependent degradation of IRF3 and autoregulatory NSP1 stability". The Journal of General Virology. 88 (Pt 2): 613–20. doi: 10.1099/vir.0.82255-0 . PMID 17251580.
- ↑ Barro M, Patton JT (May 2007). "Rotavirus NSP1 Inhibits Expression of Type I Interferon by Antagonizing the Function of Interferon Regulatory Factors IRF3, IRF5, and IRF7". Journal of Virology. 81 (9): 4473–81. doi:10.1128/JVI.02498-06. PMC 1900170 . PMID 17301153.
- ↑ Graff JW, Ettayebi K, Hardy ME (January 2009). Sherry B (ed.). "Rotavirus NSP1 Inhibits NFκB Activation by Inducing Proteasome-Dependent Degradation of β-TrCP: A Novel Mechanism of IFN Antagonism". PLOS Pathogens. 5 (1): e1000280. doi: 10.1371/journal.ppat.1000280 . PMC 2627925 . PMID 19180189.
- ↑ Bagchi P, Dutta D, Chattopadhyay S (July 2010). "Rotavirus Nonstructural Protein 1 Suppresses Virus-Induced Cellular Apoptosis To Facilitate Viral Growth by Activating the Cell Survival Pathways during Early Stages of Infection". Journal of Virology. 84 (13): 6834–6845. doi:10.1128/JVI.00225-10. PMC 2903281 . PMID 20392855.
- ↑ Bagchi P, Nandi S, Nayak MK (February 2013). "Molecular Mechanism behind Rotavirus NSP1-Mediated PI3 Kinase Activation: Interaction between NSP1 and the p85 Subunit of PI3 Kinase". Journal of Virology. 87 (4): 2358–2362. doi:10.1128/JVI.02479-12. PMC 3571490 . PMID 23221569.