Cell membrane Complex Enzyme Eukaryotic cell or cell component Microbe-host cell complex Microorganism or its component Other Other -- ion Pathway or action Protein Protein or gene Protein or gene complex Protein or protein complex Bacterial membrane or virus envelope Cell membrane Cytoplasm Eukaryotic cell or cell component Extracellular Golgi Golgi membrane Intercellular Intracellular Mitochondria Nucleocapsid/Cytoplasm Organelle Organelle -- Cell membrane Organelle -- Endoplasmic reticulum Organelle -- ER Organelle -- Golgi Organelle -- Golgi membrane Organelle -- Nucleus Organelle -- Phagolysosome Organelle -- Phagosome Organelle -- Ribosome Other Phagolysosome Phagosome Chaperone Defense, immunity protein Enzyme Enzyme activator Enzyme inhibitor Genomic S segment Infection Ligand binding or carrier Motor Nucleic acid binding Other Signal transducer Toxicity Transcription factor binding Transcription regulation Transporter Unknown IC Inferred by Curator IDA Inferred from Direct Assay IEA Inferred from Electronic Annotation IEP Inferred from Expression Pattern IGI Inferred from Genetic Interaction IMP Inferred from Mutant Phenotype IPI Inferred from Physical Interaction ISS Inferred from Sequence or Structural Similarity NAS Non-traceable Author Statement ND No biological Data available RCA inferred from Reviewed Computational Analysis TAS Traceable Author Statement NR Not Recorded Plemper RK, Erlandson KJ, Lakdawala AS, Sun A, Prussia A, Boonsombat J, Aki-Sener E, Yalcin I, Yildiz I, Temiz-Arpaci O, Tekiner B, Liotta DC, Snyder JP, Compans RW Proceedings of the National Academy of Sciences of the United States of America A target site for template-based design of measles virus entry inhibitors 200413 15056763 PubMed Santiago C, Bjorling E, Stehle T, Casasnovas JM The Journal of biological chemistry Distinct kinetics for binding of the CD46 and SLAM receptors to overlapping sites in the measles virus hemagglutinin protein 200230 12065582 PubMed Niewiesk S, Ohnimus H, Schnorr JJ, Gotzelmann M, Schneider-Schaulies S, Jassoy C, ter Meulen V The Journal of general virology Measles virus-induced immunosuppression in cotton rats is associated with cell cycle retardation in uninfected lymphocytes 1999 10466800 PubMed Grosjean I, Caux C, Bella C, Berger I, Wild F, Banchereau J, Kaiserlian D The Journal of experimental medicine Measles virus infects human dendritic cells and blocks their allostimulatory properties for CD4+ T cells 199715 9294135 PubMed Roscic-Mrkic B, Schwendener RA, Odermatt B, Zuniga A, Pavlovic J, Billeter MA, Cattaneo R Journal of virology Roles of macrophages in measles virus infection of genetically modified mice 2001 11238860 PubMed Moench TR, Griffin DE, Obriecht CR, Vaisberg AJ, Johnson RT The Journal of infectious diseases Acute measles in patients with and without neurological involvement: distribution of measles virus antigen and RNA 1988 3042879 PubMed Moll M, Klenk HD, Herrler G, Maisner A The Journal of biological chemistry A single amino acid change in the cytoplasmic domains of measles virus glycoproteins H and F alters targeting, endocytosis, and cell fusion in polarized Madin-Darby canine kidney cells 200125 11359789 PubMed Maisner A, Klenk H, Herrler G Journal of virology Polarized budding of measles virus is not determined by viral surface glycoproteins 1998 9573304 PubMed Pathak S, Illavia SJ, Khalili-Shirazi A, Webb HE Journal of the neurological sciences Immunoelectron microscopical labelling of a glycolipid in the envelopes of brain cell-derived budding viruses, Semliki Forest, influenza and measles, using a monoclonal antibody directed chiefly against galactocerebroside resulting from Semliki Forest virus infection 1990 2376758 PubMed Cathomen T, Naim HY, Cattaneo R Journal of virology Measles viruses with altered envelope protein cytoplasmic tails gain cell fusion competence 1998 9445022 PubMed Meertens N, Stoffel MH, Cherpillod P, Wittek R, Vandevelde M, Zurbriggen A Acta neuropathologica Mechanism of reduction of virus release and cell-cell fusion in persistent canine distemper virus infection 2003 12827396 PubMed Bolt G, Pedersen IR Virology The role of subtilisin-like proprotein convertases for cleavage of the measles virus fusion glycoprotein in different cell types 199820 9878618 PubMed Cathomen T, Mrkic B, Spehner D, Drillien R, Naef R, Pavlovic J, Aguzzi A, Billeter MA, Cattaneo R The EMBO journal A matrix-less measles virus is infectious and elicits extensive cell fusion: consequences for propagation in the brain 199815 9670007 PubMed Horikami SM, Curran J, Kolakofsky D, Moyer SA Journal of virology Complexes of Sendai virus NP-P and P-L proteins are required for defective interfering particle genome replication in vitro 1992 1321276 PubMed Spehner D, Drillien R, Howley PM Virology The assembly of the measles virus nucleoprotein into nucleocapsid-like particles is modulated by the phosphoprotein 19979 9191839 PubMed Tober C, Seufert M, Schneider H, Billeter MA, Johnston IC, Niewiesk S, ter Meulen V, Schneider-Schaulies S Journal of virology Expression of measles virus V protein is associated with pathogenicity and control of viral RNA synthesis 1998 9733853 PubMed Vincent S, Gerlier D, Manie SN Journal of virology Measles virus assembly within membrane rafts 2000 11024118 PubMed Stallcup KC, Wechsler SL, Fields BN Journal of virology Purification of measles virus and characterization of subviral components 1979 113558 PubMed Sidhu MS, Menonna JP, Cook SD, Dowling PC, Udem SA Virology Canine distemper virus L gene: sequence and comparison with related viruses 1993 8438585 PubMed Das T, Schuster A, Schneider-Schaulies S, Banerjee AK Virology Involvement of cellular casein kinase II in the phosphorylation of measles virus P protein: identification of phosphorylation sites 19951 7645214 PubMed Huber M, Cattaneo R, Spielhofer P, Orvell C, Norrby E, Messerli M, Perriard JC, Billeter MA Virology Measles virus phosphoprotein retains the nucleocapsid protein in the cytoplasm 1991 1656588 PubMed Gombart AF, Hirano A, Wong TC Virus research Nucleoprotein phosphorylated on both serine and threonine is preferentially assembled into the nucleocapsids of measles virus 1995 7483823 PubMed Gombart AF, Hirano A, Wong TC Journal of virology Conformational maturation of measles virus nucleocapsid protein 1993 7685410 PubMed Baker KA, Dutch RE, Lamb RA, Jardetzky TS Molecular cell Structural basis for paramyxovirus-mediated membrane fusion 1999 10198633 PubMed Parks CL, Lerch RA, Walpita P, Wang HP, Sidhu MS, Udem SA Journal of virology Analysis of the noncoding regions of measles virus strains in the Edmonston vaccine lineage 2001 11134305 PubMed Karp CL Immunological reviews Measles: immunosuppression, interleukin-12, and complement receptors 1999 10399067 PubMed Manchester M, Liszewski MK, Atkinson JP, Oldstone MB Proceedings of the National Academy of Sciences of the United States of America Multiple isoforms of CD46 (membrane cofactor protein) serve as receptors for measles virus 199415 8134365 PubMed Vincent S, Spehner D, Manie S, Delorme R, Drillien R, Gerlier D Virology Inefficient measles virus budding in murine L.CD46 fibroblasts 199920 10600591 PubMed Liston P, Briedis DJ Journal of virology Ribosomal frameshifting during translation of measles virus P protein mRNA is capable of directing synthesis of a unique protein 1995 7474085 PubMed Liston P, DiFlumeri C, Briedis DJ Virus research Protein interactions entered into by the measles virus P, V, and C proteins 1995 8578862 PubMed Horikami SM, Moyer SA Current topics in microbiology and immunology Structure, transcription, and replication of measles virus 1995 7789161 PubMed Radecke F, Billeter MA Virology The nonstructural C protein is not essential for multiplication of Edmonston B strain measles virus in cultured cells 19961 8599233 PubMed Measles virus Function: . The measles virus is a spherical, nonsegmented, single-stranded RNA virus in the Morbillivirus family. The entire genome of the Measles virus has been sequenced and is approximately 16,000 nucleotides long. It encodes six structural proteins: nucleoprotein (N), phosphoprotein (P), matrix protein (M), fusion protein (F), hemagglutinin (H) and polymerase (L). The P cistron also encodes three nonstructural proteins C, V, and R whose functions remain poorly defined. The genomic RNA, encapsidated by N, and associated with the two RNA polymerase sub-units L and P, forms the ribonucleoprotein (RNP) core of the virus. The H and F proteins, with M protein underlying the phospholipids bilayer, constitute the virus envelope.(Radecke et al., 1996)(Liston et al., 1995)(Horikami et al., 1995)(Liston et al., 1995)(Vincent et al., 1999) The H protein. Virus particle binding to the host cell membrane Function: . Infection of the host cells with Measles virus begins with attachment of the virus particles to receptors on surface of the host plasma membrane.The virus hemagglutinin H (glycoprotein, 78 kd) binds to the human CD46 receptor which is a disulfide-linked homodimer of several isoforms and which serves as a co-factor for serine protease degradation of C3b and C4b complement proteins, bringing about inhibition of complement activation on host cells.Interaction of the H protein with its cellular receptor CD150 triggers the conformational changes within the F protein.(Karp, 1999)(Manchester et al., 1994) The F protein. Viral envelope and host cell plasma membrane fusion Function: . The fusion F protein (glycoprotein, 60 kd) is F1 - F2 heterodimer that leads to insertion of the hydrophobic fusion domain into the target host cell membrane. Conformational changes then occur and the N terminus of the F1 subunit becomes anchored in the membrane of the host cell.The viral envelope then fuses with the plasma membrane of the host cell, allowing the virus to enter the cell.(Baker et al., 1999) Viral RNA transcription and translation Function: . Fusion enables entry of the virus into the host cell. Once inside, the process of virus uncoating releases the RNA inside the host cell. The genome of Measles virus comprises a single-stranded RNA molecule of negative polarity. Viral mRNA is transcribed directly from the genomic RNA. The viral mRNA is then translated to produce viral proteins. Viral genes direct the production of proteins by the cellular machinery.(Parks et al., 2001) The N protein Function: Nucleic acid binding. The N protein (nucleoprotein, 60 kd), the most abundant of the viral proteins, is synthesized on free ribosome and folded in the host cytoplasm. Free N protein is phosphorylated on serine whereas nucleocapsid associated N is phosporelated on serine and threonine.N protein can be transported to the nucleus but is usually retained in the cytoplasm by binding to P protein.(Gombart et al., 1993)(Gombart et al., 1995)(Huber et al., 1991) The P protein Function: Unknown. The P protein (phosphoprotein, 72 kd) is activated by phosphorylation. Serine/threonine phosphorylation of P is carried out by cellular kinases, primarily casein kinase II.(Das et al., 1995) The L protein Function: Nucleic acid binding. The large L protein (200 kd) is a highly conserved and contains a motif common to the RNA polymerases of negative-strand viruses.The L protein is present in small quantities in the infected cell, interacts with and functions in association with P, and is part of the viral nucleocapsid in the cell.The N, P, and L proteins, in association with the RNA genome, form the transcriptional and replicative unit or ribonucleoparticle.(Sidhu et al., 1993)(Stallcup et al., 1979)(Vincent et al., 2000) Viral RNA replication Function: . The viral replication of the entire genome requires production of a full-length, positive-sense antigene as the template for synthesis of negative-sense genomic RNAs. Viral RNA replication then involves full length strand synthesis. Full length strand is coated with nucleocapsid proteins as they are made.(Horikami et al., 1995) The C and V proteins Function: . The P gene of Measles virus encodes C (21 kd) and V (40 kd) proteins in edition to P. Both proteins interact with cellular proteins.The V protein is distributed in the cytoplasm of infected cells. The V protein effects N-P interaction (this may be dependent on its interaction with N protein) acting to balance accumulation of viral gene products.The C and V proteins play a role in regulation of transcription and replication, possibly by modulating the intracellular environment for replication.The P protein oligomerizes and binds to L, N proteins and RNA to form the replicative complex.(Liston et al., 1995)(Tober et al., 1998)(Spehner et al., 1997) Nucleocapsid assembly Function: . The many fine details of current view of nucleocapsid assembly remain to be understood.The assembly of nucleocapsid requires specific interactions of newly synthesized viral genomes with a subset of the viral structural proteins, the N, P, and L proteins, as well as interactions between each of these three proteins. The general model is that RNA encapsidation by N is a process coupled to genome replication. A complex between the P and L proteins replicates the parental genome and simultaneously as nascent genomes appear they are enwrapped by N donated from a complex of the N and P proteins. (PMID: 1321276).RNA encapsidation signals and or the RNA replication process itself are such factors whose role in nucleocapsid formation remains to be better defined.(Spehner et al., 1997)(Horikami et al., 1992) Virus particle assembly Function: . The nucleocapsid assembly occurs in the cytoplasm and is then directed to the host plasma membrane, where it can contact the viral envelope protein complex.(Spehner et al., 1997) The M protein Function: . M viral protein (matrix protein, 38 kd) is synthesized on free cytoplasmic ribosomes.The M protein lines the inner surface of the host cell plasma membrane, from which the Measles virus lipid envelope will be derived during the budding process. The M protein appears to act by concentrating the F and H proteins, as well as the nucleocapsid, at the sites of virus assembly.(Horikami et al., 1995)(Cathomen et al., 1998) The H and F proteins-synthesis/maturation Function: . The H and F proteins are synthesized on membrane-bound ribosomes, mature through the endoplasmic reticulum and the Golgi, and become integral host plasma membrane proteins. The F protein is synthesized as an inactive precursor (F0) that is cleaved in the trans-Golgi network to form the biologically active protein consisting of the disulfide-linked subunits F1 and F2. The nucleocapsid is packaged into an envelope protein complex composed of the two integral membrane glycoproteins H and F and the inner-membrane-associated M protein. Final Measles virus assembly would occur at the plasma membrane just prior to the virus budding.(Horikami et al., 1995)(Bolt et al., 1998) Virus particles escape the host cell by budding Function: . Expression of the H and F glycoproteins at the host cell surface is required for successful budding, which involves complex interactions between all viral proteins.The M protein appears to interact with the intracytoplasmic regions of H and F transmembrane glycoproteins, perhaps stabilizing or organizing the membrane environment in preparation for budding of virions.After intracellular assembly of these complexes, virus particles are released by budding out from the host cell membrane.Measles virus obtains its lipid envelope from the host cell plasma membrane during the budding process.The budding process of Measles virus is not fully understood and only little evidence is available.(Cathomen et al., 1998)(Meertens et al., 2003)(Cathomen et al., 1998)(Pathak et al., 1990) Virus spread Function: . The two Measles virus surface H and F glycoproteins are abundantly expressed on the basolateral surface of epithelia. Both glycoproteins contain a tyrosine-based sorting signal in their cytoplasmic domains, which is required for basolateral protein expression and for the fusogenic activity of H and F complexes in host cells. The F and H proteins mediate virus spread from epithelia by direct cell-to-cell contacts and cell fusion.Measles virus disseminates to draining lymph nodes via infected macrophages and replicates in local lymphatic tissues followed by systemic spread of infection.(Maisner et al., 1998)(Moll et al., 2001)(Moench et al., 1988)(Roscic-Mrkic et al., 2001) Immune suppression and cell apoptosis Function: . Measles causes a profound immune suppression which is responsible for the high morbidity and mortality induced by secondary infections. The mechanisms which contribute to the loss of the allostimulatory function of dendritic cells (DC) include both virus release and active suppression mediated by Measles virus-infected DC. The carriage of Measles virus by DC may facilitate virus spreading to secondary lymphoid organs and virus replication in DC may play a central role in the general immune suppression observed during measles disease.Immune suppression during acute measles is a well-documented phenomenon in man. Measles virus-infected DC undergo apoptosis. So far, it is not clear whether apoptosis is an effect induced by Measles virus in particular in contrast to other viruses or whether apoptosis of thymocytes, activated T cells and DCs is a general regulatory mechanism of the immune response.(Grosjean et al., 1997)(Niewiesk et al., 1999)