Abstract
Alphaviruses are enveloped viruses containing a single positive strand RNA molecule as genome. Expression vectors based on alphaviruses have been developed from Sindbis virus (SIN), Semliki Forest virus (SFV), and Venezuelan Equine Encephalitis virus (VEE). Alphavirus self-replicating RNA containing heterologous genes can be synthesized in vitro from plasmids in which the recombinant alphavirus replicon cDNA sequences are under the control of a prokaryotic promoter. When this self-amplifying RNA is transfected into cells a high level expression of the heterologous proteins/RNA is obtained. The alphavirus vectors can be delivered directly as naked RNA, as naked DNA and as viral particles. In order to encapsidate the alphaviral recombinant RNA into particles, packaging systems have been developed which supply the structural proteins of the virus in trans. Delivery of alphavirus as naked DNA is based on DNA/RNA layered vectors in which the recombinant replicon is transcribed from an RNA polymerase-II promoter in the nucleus of the transfected cell. Alphavirus vectors have been used to express proteins with many different purposes, which include large-scale production, characterization, functional studies and virus assembly. The ability of alphavirus to infect neurons has opened many possibilities for the study of protein function in these cells. In addition, alphavirus vectors can also be used for gene delivery in vivo with potential applications in vaccination and gene therapy, although some improvements in the present technology are necessary for this latter purpose. Alphavirus sequences have also been used to engineer cell lines for diagnostic virus detection.
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Agapov, E. V., Frolov, I., Lindebach, B. D., Prágal, B. M., Schlesinger, S., and Rice, C. M. (1998). NoncytopathicSindbis virus RNA vectors for heterologous gene expression. Proc. Natl. Acad. Sci. USA. 95:12989–12994.
Altman-Hamamdzic, S., Groseclose, C., Ma, J. X., Hamamdzic, D., Vrindavanam, N. S., Middaugh, L. D., Parratto, N. P., and Sallee, F. R. (1997). Expression of β-galactosidase in mouse brain: utilization of a novel nonreplicative Sindbis virus vector as a neuronal gene delivery system. Gene Ther. 4:815–822.
Altmeyer, R., Mordelet, E., Girard, M., and Vidal, C. (1999). Expression and detection of macrophage-tropic HIV-1 gp120 in the brain using conformation-dependent antibodies. Virology. 259:314–323.
Asselin-Paturel, C., Lassau, N., Guinebretiere, J. M., Zhang, J., Gay, F., Bex, F., Hallez, S., Leclere, J., Peronneau, P., Mami-Chouaib, F., and Chouaib, S. (1998). Transfer of the murine interleukin-12 gene in vivo by a Semliki Forest virus vector induces B16 tumor regression through inhibition of tumor blood vessel formation monitored by Doppler ultrasonography. Gene Ther. 5:606–615.
Berglund, P., Fleeton, M. N., Smerdou, C., and Liljeström, P. (1999). Immunization with recombinant Semliki Forest virus induces protection against influenza challenge in mice. Vaccine. 17:497–507.
Berglund, P., Quesada-Rholander, M., Putkonen, P., Biberfeld, G., Thorstensson, R., and Liljeström, P. (1997). Outcome of immunization of cynomolgus monkeys with recombinant Semliki Forest virus encoding human immunodeficiency virus type 1 envelope protein and challenge with a high dose of SHIV-4 virus. AIDS Res. Hum. Retrovir. 13:1487–1495.
Berglund, P., Sjöberg, M., Garoff, H., Atkins, G. J., Sheahan, B. J., and Liljeström, P. (1993). Semliki Forest virus expression system: production of conditionally infectious recombinant particles. Bio/Technology. 11:916–920.
Berglund, P., Smerdou, C., Fleeton, M. N., Tubulekas, I., and Liljeström, P. (1998). Enhancing immune responses using suicidal DNA vaccines. Nat. Biotech. 16:562–565.
Blasey, H. D., Lundström, K., Tate, S., and Bernard, A. R. (1997). Recombinant protein production using the Semliki Forest virus expression system. Cytotechnol. 24:65–72.
Brand, D., Lemiale, F., Turbica, I., Buzelay, L., Brunet, S., and Barin, F. (1998). Comparative analysis of humoral immune responses to HIV type 1 envelope glycoproteins in mice immunized with a DNA vaccine, recombinant Semliki Forest virus RNA, or recombinant Semliki Forest virus particles. AIDS Res. Hum. Retrovir. 14:1369–1377.
Brandt, E. R., Linnane, A. W., and Devenish, R. J. (1994). Expression of IFN A genes in subpopulations of peripheral blood cells. Brit. J. Haematol. 86:717–725.
Bredenbeek, P. J., Frolov, I., Rice, C. M., and Schlesinger, S. (1993). Sindbis virus expression vectors: packaging of RNA replicons by using defective helper RNAs. J. Virol. 67:6439–6446.
Caley, I. J., Betts, M. R., Davis, N. L., Swanstrom, R., Frelinger, J. A., and Johnston, R. E. (1999). Venezuelan equine encephalitis virus vectors expressing H1V-1 proteins: vector design strategies for improved vaccine efficacy. Vaccine. 17:3124–3135.
Caley, I. J., Betts, M. R., Irlbeck, D. M., Davis, N. L., Swanstrom, R., Frelinger, J. A., and Johnston, R. E. (1997). Humoral, mucosal, and cellular immunity in response to a human immunodeficiency virus type 1 immunogen expressed by a Venezuelan equine encephalitis virus vaccine vector. J. Virol. 71:3031–3038.
Chen, J. P., Miller, D., Katow, S., and Frey, T. K. (1995). Expression of the rubella virus structural proteins by an infectious Sindbis virus vector. Archiv. Virol. 140:2075–2084.
Chen, M., Hu, K. F., Örvell, C., Morein, B., and Liljeström, P. (1999). Intranasal vaccination with recombinant Semliki Forest virus protects against respiratory syncitial virus infection: Effects of IL-12 co-delivery. Submitted.
Cheng, E. H., Kirsch, D. C., Clem, R. J., Ravi, R., Kastan, M. B., Bedi, A., Ueno, K., and Hardwick, J. M. (1997). Conversion of Bcl-2 to a Bax-like death effector by caspases. Science. 278:1966–1968.
Colmenero, P., Liljeström, P., and Jondal, M. (1999). Induction of P815 tumor immunity by recombinant Semliki Forest virus expressing the PIA gene. Gene Ther. 6:1728–1733.
Colombage, G., Hall, R., Pavy, M., and Lobigs, M. (1998). DNA-based and alphavirus-vectored immunisation with prM and E proteins elicits long-lived and protective immunity against the flavivirus Murray Valley encephalitis virus. Virology. 250:151–163.
Cook, D. G., Sung, J. C., Golde, T. E., Felsenstein, K. M., Wojczyk, B. S., Tanzi, R. E., Trojanowski, J. Q., Lee, V. M., and Doms, R. W. (1996). Expression and analysis of presenilin 1 in a human neuronal system: localization in cell bodies and dendrites. Proc. Natl. Acad. Sci. USA. 93:9223–9228.
Dalemans, W., Delers, A., Delmelle, C., Denamur, F., Meykens, R., Thiriart, C., Veenstra, S., Francotte, M., Bruck, C., and Cohen, J. (1995). Protection against homologous influenza challenge by genetic immunization with SFV-RNA encoding Flu-HA. Ann. N. Y. Acad. Sci. 772:255–256.
Davis, N. L., Brown, K. W., and Johnston, R. E. (1996). A viral vaccine vector that expresses foreign genes in lymph nodes and protects against mucosal challenge. J. Virol. 70:3781–3787.
Davis, N. L., Powell, N., Greenwald, G. F., Willis, L. V., Johnson, B. J. B., Smith, J. F., and Jonhston, R. E. (1991). Attenuating mutations in the E2 glycoprotein gene of Venezuelan equine encephalitis virus: Construction of single and multiple mutants in a full-length cDNA clone. Virology. 183:20–31.
Davis, N. L., Willis, L. V., Smith, J. F., and Johnston, R. E. (1989). In vitro synthesis of infectious Venezuelan equine encephalitis virus RNA from a cDNA clone: Analysis of a viable deletion mutant. Virology. 171:189–204.
de Hoop, M. J., Olkkonen, V. M., Ikonen, E., Williamson, E., von Poser, C., Meyn, L., and Dotti, C. G. (1994). Semliki Forest virus as a tool for protein expression in cultured rat hippocampal neurons. Gene Ther. 1:S28–31.
DiCiommo, D. P. and Bremner, R. (1998). Rapid, high level protein production using DNA-based Semliki Forest virus vectors. J. Biol. Chem. 273:18060–18066.
Donnelly, S. M., Sheahan, B. J., and Atkins, G. J. (1997). Long-term effects of Semliki Forest virus infection in the mouse central nervous system. Neuropathol. Appl. Neurobiol. 23:235–241.
Dryga, S. A., Dryga, O. A., and Schlesinger, S. (1997). Identification of mutations in a Sindbis virus variant able to establish persistent infection in BHK cells: the importance of a mutation in the nsP2 gene. Virology. 228:74–83.
Dubensky, T. W. Jr., Driver, D. A., Polo, J. M., Belli, B. A., Latham, E. M., Ibanez, C. E., Chada, S., Brumm, D., Banks, T. A., Mento, S. J., Jolly, D. J., and Chang, S. M. (1996). Sindbis virus DNA-based expression vectors: utility for in vitro and in vivo gene transfer. J. Virol. 70:508–519.
Dubuisson, J., Hsu, H. H., Cheung, R. C., Greenberg, H. B., Russell, D. G., and Rice, C. M. (1994). Formation and intracellular localization of hepatitis C virus envelope glycoprotein complexes expressed by recombinant vaccinia and Sindbis viruses. J. Virol. 68:6147–6160.
Dubuisson, J. and Rice, C. M. (1993). Sindbis virus attachment: isolation and characterization of mutants with impaired binding to vertebrate cells. J. Virol. 67:3363–3374.
Ehrengruber, M. U., Lundström, K., Schweitzer, C., Heuss, C., Schlesinger, S., and Gähwiler, B. H. (1999). Recombinant Semliki Forest virus and Sindbis virus efficiently infect neurons in hippocampal slice cultures. Proc. Natl. Acad. Sci. USA. 96:7041–7046.
Evans, R. J., Lewis, C., Virginio, C., Lundström, K., Buell, G., Surprenant, A., and North, R. A. (1996). Ionic permeability of, and divalent cation effects on, two ATP-gated cation channels (P2X receptors) expressedin mammalian cells. J. Physiology. 497:413–422.
Filocamo, G., Pacini, L., Nardi, C., Bartholomew, L., Scaturro, M., Delmastro, P., Tramontano A., De Francesco, R., and Migliaccio, G. (1999). Selection of functional variants of the NS3-NS4A protease of hepatitis C virus by using chimeric Sindbis viruses. J. Virol. 73:561–575.
Fleeton, M. N., Chen, M., Klingström, J., Berglund, P., Murphy, A. M., Rhodes, G., Parker, S. E., Atkins, G. J., and Liljeström, P. (1999a). Protection from viral infection upon vaccination with naked self-replicating RNA. Submitted.
Fleeton, M. N., Liljeström, P., Sheahan, B. J., and Atkins, G. J. (1999b). Protective responses induced in mice by lou** ill virus prME and NS1 antigens expressed from Semliki Forest virus vectors. J. Gen. Virol. 81:000–000.
Fleeton, M. N., Sheahan, B. J., Gould, E. A., Atkins, G. J., and Liljeström, P. (1999c). Recombinant Semliki Forest virus particles encoding the prME or NS1 proteins of lou** ill virus protect mice from lethal challengc, J. Gen. Virol. 80:1189–1198.
Frolov, I., Agapov, E., Hoffman, T. A. J., Prágal, B. M., Lippa, M., Schlesinger, S., and Rice, C. M. (1999). Selection of RNA replicons capable of persistent noncytopathic replication in mammalian cells. J. Virol. 73:3854–3865.
Frolov, I., Frolova, E., and Schlesinger, S. (1997). Sindbis virus replicons and Sindbis virus: assembly of chimeras and of particles deficient in virus RNA. J. Virol. 71:2819–2829.
Frolov, I. and Schlesinger, S. (1994a). Translation of Sindbis virus mRNA: effects of sequences downstream of the initiating codon. J. Virol. 68:8111–8117.
Frolov, I. and Schlesinger, S. (1994b). Comparison of the effects of Sindbis virus and Sindbis virus replicons on host cell protein synthesis and cytopathogenicity in BHK cells. J. Virol. 68:1721–1727.
Frolov, I. and Schlesinger, S. (1996). Translation of Sindbis virus mRNA: analysis of sequences downstream of the initiating AUG codon that enhance translation. J. Virol. 70:1182–1190.
Frolova, E., Frolov, I., and Schlesinger, S. (1997). Packaging signals in alphavirases. J. Virol. 71:248–258.
Gates, M. C., Sheahan, B. J., and Atkins, G. J. (1984). The pathogenicity of the M9 mutant of Semliki Forest virus in immune-compromised mice. J. Gen. Virol. 65:73–80.
Giraud, A., Ataman-Onal, Y., Battail, N., Piga, N., Brand, D., Mandrand, B., and Verrier, B. (1999). Generation of monoclonal antibodies to native human immunodeficiency virus type 1 envelope glycoprotein by immunization of mice with naked RNA. J. Virol. Methods. 79:75–84.
Glasgow, G. M., McGee, M. M., Sheahan, B. J., and Atkins, G. J. (1997). Death mechanisms in cultured cells infected by Semliki Forest virus. J. Gen. Virol. 78:1559–1563.
Glasgow, G. M., McGee, M. M., Tarbatt, C. J., Mooney, D. A., Sheahan, B. J., and Atkins, G. J. (1998). The Semliki Forest virus vector induces p53-independent apoptosis. J. Gen. Virol. 79:2405–2410.
Grandgirard, D., Studer, E., Monney, L., Belser, T., Fellay, I., Borner, C., and Michel, M. R. (1998). Alphaviruses induce apoptosis in Bcl-2-overexpressing Cells: evidence for a caspase-mediated, proteolytic inactivation of Bcl-2. EMBO J. 17:1268–1278.
Griffin, D. E. and Hardwick, J. M. (1997). Regulators of apoptosis on the road to persistent alphavirus infection. Ann. Rev. Microbiol. 51:565–592.
Gwag, B. J., Kim, E. Y., Ryu, B. R., Won, S. J., Ko, H. W., Oh, Y. J., Cho, Y. G., Ha, S. J., and Sung, Y. C. (1998). A neuron-specific gene transfer by a recombinant defective Sindbis virus. Molec. Brain Res. 63:53–61.
Hahn, C. S., Hahn, Y. S., Braciale, T. J., and Rice, C. M. (1992). Infectious Sindbis virus transient expression vectors for studying antigen processing and presentation. Proc. Natl. Acad. Sci. USA. 89:2679–2683.
Haijou, M., Hill, K. R., Subramaniam, S. V., Hu, J. Y., and Raju, R. (1996). Nonhomologous RNA-RNA recombination events at the 3′ nontranslated region of the Sindbis virus genome: hot spots and utilization of nonviral sequences. J. Virol. 70:5153–5164.
Hariharan, M. J., Driver, D. A., Townsend, K., Brumm, D., Polo, J. M., Belli, B. A., Catton, D. J., Hsu, D., Mittelstaedt, D., McCormack, J. E., Karavodin, L., Dubensky, T. W. Jr., Chang, S. M., and Banks, T. A. (1998). DNA immunization against herpes simplex virus: enhanced efficacy using a Sindbis virus-based vector. J. Virol. 72:950–958.
Heino, P., Dillner, J., and Schwartz, S. (1995). Human papillomavirus type 16 capsid proteins produced from recombinant Semliki Forest virus assemble into virus-like particles. Virology. 214:349–359.
Herweijer, H., Latendresse, J. S., Williams, P., Zhang, G. F., Danko, I., Schlesinger, S., and Wolff, J. A. (1995). A plasmid-based self-amplifying Sindbis virus vector. Hum. Gen. Ther. 6:1161–1167.
Hevey, M., Negley, D., Pushko, P., Smith, J., and Schmaljohn, A. (1998). Marburg virus vaccines based upon alphavirus replicons protect guinea pigs and nonhuman primates. Virology. 251:28–37.
Higgs, S., Olson, K. E., Klimowski, L., Powers, A. M., Carlson, J. O., Possee, R. D., and Beaty, B. J. (1995). Mosquito sensitivity to a scorpion neurotoxin expressed using an infectious Sindbis virus vector. Insect Mol. Biol. 4:97–103.
Higgs, S., Rayner, J. O., Olson, K. E., Davis, B. S., Beaty, B. J., and Blair, C. D. (1998). Engineered resistance in Aedes aegypti to a West African and a South American strain of yellow fever virus. Am. J. Trop. Med. Hyg. 58:663–670.
Hill, K. R., Hajjou, M., Hu, J. Y., and Raju, R. (1997). RNA-RNA recombination in Sindbis virus: roles of the 3′ conserved motif, poly(A) tail, and nonviral sequences of template RNAs in polymerase recognition and template switching. J. Virol. 71:2693–2704.
Hovius, R., Tairi, A. P., Blasey, H., Bernard, A., Lundstrom, K., and Vogel, H. (1998). Characterization of a mouse serotonin 5-HT3 receptor purified from mammalian cells. J. Neurochem. 70:824–834.
Ijima, Y., Ohno, K., Ikeda, H., Sawai, K., Levin, B., and Meruelo, D. (1999). Cell-specific targeting of a thymidine kinase/ganciclovir gene therapy system using a recombinant Sindbis virus vector. Int. J. Cancer. 80:110–118.
Ivanova, L., Schlesinger, S., and Olivo, P. D. (1999). Regulated expression of a Sindbis virus replicon by herpesvirus promoters. J. Virol. 73:1998–2005.
Jain, S. K., DeCandido, S., and Kielian, M. (1991). Processing of the p62 envelope precursor protein of Semliki Forest virus. J. Biol. Chem. 266:5756–5761.
Jiang, W., Venugopal, K., and Gould, E. A. (1995). Intracellular interference of tick-borne flavivirus infection by using a single-chain antibody fragment delivered by recombinant Sindbis virus. J. Virol. 69:1044–1049.
Johanning, F. W., Corny, R. M., Lo Buglio, A. F., Wright, M., Sumerel, L. A., Pike, M. J., and Curiel, D. T. (1995). A Sindbis virus mRNA polynucleotide vector achieves prolonged and high level heterologous gene expression in vivo. Nucl. Acids Res. 23:1495–1501.
Kaluza, G., Lell, G., Reinacher, M., Stitz, L., and Willems, W. R. (1987). Neurogenic spread of Semliki Forest virus in mice. Archiv. Virol. 93:97–110.
Kamrud, K. I., Hooper, J. W., Elgh, F., and Schmaljohn, C. S. (1999). Comparison of the protective efficacy of naked DNA, DNA-based Sindbis replicon, and packaged Sindbis replicon vectors expressing hantavirus structural genes in hamsters. Virology. 263:209–219.
Kamrud, K. I., Olson, K. E., Higgs, S., Carlson, J. O., and Beaty, B. J. (1998). Use of the Sindbis replicon system for expression of LaCrosse virus envelope proteins in mosquito cells. Archiv. Virol. 143:1365–1377.
Kamrud, K. I., Powers, A. M., Higgs, S., Olson, K. E., Blair, C. D., Carlson, J. O., and Beaty, B. J. (1995). The expression of chloramphenicol acetyltransferase in mosquitoes and mosquito cells using a packaged Sindbis replicon system. Exp. Parasitol. 81:394–403.
Kohno, A., Emi, N., Kasai, M., Tanimoto, M., and Saito, H. (1998). Semliki Forest virus-based DNA expression vector transient protein production followed by cell death. Gene Ther. 5:415–418.
Kuhn, R. J., Niesters, H. G., Hong, Z., and Strauss, J. H. (1991). Infectious RNA transcripts from Ross River virus cDNA clones and the construction and characterization of defined chimeras with Sindbis virus. Virology. 182:430–441.
Lebedeva, I., Fujita, K., Nihrane, A., and Silver, J. (1997). Infectious particles derived from Semliki Forest virus vectors encoding murine leukemia virus envelopes. J. Virol. 71:7061–7067.
Lee, A. H., Suh, Y. S., Sung, J. H., Yang, S. H., and Sung, Y. C. (1997). Comparison of various expression plasmids for the induction of immune response by DNA immunization. Mol. Cells. 7:495–501.
Lee, S., Owen, K. E., Choi, H. K., Lee, H., Lu, G. G., Wengler, G., Brown, D. T., Rossmann, M. G., and Kuhn, R. J. (1996). Identification of a protein binding site on the surface of the alphavirus nucleocapsid and its implication in virus assembly. Structure. 4:531–541.
Levine, B., Goldman, J. E., Jiang, H. H., Griffin, D. E., and Hardwick, J. M. (1996). Bcl-2 protects mice against fatal alphavirus encephalitis. Proc. Nat. Acad. Sci. USA. 93:4810–4815.
Levine, B., Huang, Q., Isaacs, J. T., Reed, J. C., Griffin, D. E., and Hardwick, J. M. (1993). Conversion of lytic to persistent alphavirus infection by the bcl-2 cellular oncogene. Nature. 361:739–742.
Lewis, J., Oyler, G. A., Ueno, K., Fannjiang, Y. R., Chau, B. N., Vornov, J., Korsmeyer, S. J., Zou, S. F., and Hardwick, J. M. (1999). Inhibition of virus-induced neuronal apoptosis by Bax. Nat. Med. 5:832–835.
Li, K. J. and Garoff, H. (1996). Production of infectious recombinant Moloney murine leukemia virus particles in BHK cells using Semliki Forest virus-derived RNA expression vectors. Proc. Natl. Acad. Sci. USA. 93:11658–11663.
Li, K. J. and Garoff, H. (1998). Packaging of intron containing genes into retrovirus vectors by alphavirus vectors. Proc. Natl. Acad. Sci. USA. 95:3650–3654.
Liang, X. H., Jiang, H. H., and Levine, B. (1997). Expression of a biologically active antiviral antibody using a Sindbis virus vector system. Mol. Immunol. 34:907–917.
Liang, X. H., Kleeman, L. K., Jiang, H. H., Gordon, G., Goldman, J. E., Berry, G., Herman, B., and Levine, B. (1998). Protection against fatal Sindbis encephalitis by beclin, a novel Bcl-2-interacting protein. J. Virol. 72:8586–8596.
Liao, C. L., Lin, Y. L., Wang, J. J., Huang, Y. L., Yeh, C. T., Ma, S. H., and Chen, L. K. (1997). Effect of enforced expression of human bcl-2 on Japanese encephalitis virus-induced apoptosis in cultured cells. J. Virol. 71:5963–5971.
Liljeström, P. and Garoff, H. (1991). A new generation of animal cell expression vectors based on the Semliki Forest virus replicon. Bio/Technology. 9:1356–1361.
Liljeström, P., Lusa, S., Huylebroeck, D., and Garoff, H. (1991). In vitro mutagenesis of a full-length cDNA clone of Semliki Forest virus: the 6,000-molecular-weight membrane protein modulates virus release. J. Virol. 65:4107–4113.
Lindenbach, B. D. and Rice, C. M. (1997). Trans-complementation of yellow fever virus NS1 reveals a role in early RNA replication. J. Virol. 71:9608–9617.
Lobigs, M. and Garoff, H. (1990). Fusion function of the Semliki Forest virus spike is activated by proteolytic cleavage of the envelope glycoprotein precursor p62. J. Virol. 64:1233–1240.
London, S. D., Schmaljohn, A. L., Dalrymple, J. M., and Rice, C. M. (1992). Infectious enveloped RNA virus antigenic chimeras. Proc. Natl. Acad. Sci. USA. 89:207–211.
Lopez, S., Yao, J. S., Kuhn, R. J., Strauss, E. G., and Strauss, J. H. (1994). Nucleocapsid-glycoprotein interactions required for assembly of alphaviruses. J. Virol. 68:1316–1323.
Lundström, K. (1999). Alphavirus as tools in neurobiology and gene therapy. J. Rec. Signal Transd. Res. 19:673–686.
Lundström, K., Michel, A., Blasey, H., Bernard, A. R., Hovius, R., Vogel, H., and Surprenant, A. (1997). Expression of ligand-gated ion channels with the Semliki Forest virus expression system. J. Rec. Signal Transd. Res. 17:115–126.
Lundström, K., Mills, A., Allet, E., Ceszkowski, K., Agudo, G., Chollet, A., and Liljeström, P. (1995a). High-level expression of G protein-coupled receptors with the aid of the Semliki Forest virus expression system. J. Rec. Signal Transd. Res. 15:23–32.
Lundström, K., Mills, A., Buell, G., Allet, E., Adami, N., and Liljeström, P. (1994). High-level expression of the human neurokinin-1 receptor in mammalian cell lines using the Semliki Forest virus expression system. Eur. J. Biochem. 224:917–921.
Lundström, K., Richards, J. G., Pink, J. R., and Jenck, F. (1999). Efficient in vivo expression of a reporter gene in rat brain after injection of recombinant rcplicon-deficient Semliki Forest virus. Gene Ther. Mol. Biol. 3:15–23.
Lundström, K. and Turpin, M. P. (1996). Proposed shizophrenia-related gene polymorphism: expression of the Ser9Gly mutant human dopamine D3 receptor with the Semliki Forest virus system. Biochem. Biophys. Res. Commun. 225:1068–1072.
Lundström, K., Turpin, M. P., Large, C., Robertson, G., Thomas, P., and Lewell, X. Q. (1998). Map** of dopamine D3 receptor binding site by pharmacological characterization of mutants expressed in CHO cells with the Semliki Forest virus system. J. Rec. Signal Transd. Res. 18:133–150.
Lundström, K., Vargas, A., and Allet, B. (1995b). Functional activity of a biotinylated human neurokinin 1 receptor fusion expressed in the Semliki Forest virus system. Biochem. Biophys. Res. Comm. 208:260–266.
Maletic-Savatic, M., Malinow, R., and Svoboda, K. (1999). Rapid dendritic morphogenesis in CA1 hippocampal dendrites induced by synaptic activity. Science. 283:1923–1927.
Malherbe, P., Kratzeisen, C., Lundström, K., Richards, J. G., Faull, R. L. M., and Mutel, V. (1999). Cloning and functional expression of alternative spliced variants of the human metabotropic glutamate receptor 8. Mol. Brain Res. 67:201–210.
Marheineke, K., Lenhard, T., Haase, W., Beckers, T., Michel, H., and Reilander, H. (1998). Characterization of the human gonadotropin-releasing hormone receptor heterologously produced using the baculovirus/insect cell and the Semliki Forest virus systems. Cell. Mol. Neurobiol. 18:509–524.
McCue, L. A. and Anders, D. G. (1998). Soluble expression and complex formation of proteins required for HCMV DNA replication using the SFV expression system. Protein Expression & Purification. 13:301–312.
Michel, A. D., Lundström, K., Buell, G., N., Surprenant, A., Valera, S., and Humphrey, P. P. (1996). The binding characteristics of a human bladder recombinant P2X purinoreceptor, labelled with [3 H]-αβmeATP, [35S]-ATPγS or [33P]-ATP. British J. Pharmacol. 117:1254–1260.
Monastyrskaia, K., Goepfert, F., Hochstrasser, R., Acuna, G., Leighton, J., Pink, J. R., and Lundström, K. (1999). Expression and intracellular localisation of odorant receptors in mammalian cell lines using Semliki Forest virus vectors. J, Rec. Signal Transd. Res. 19:687–701.
Mor, G., Yamshchikov, G., Sedegah, M., Takeno, M., Wang, R., Houghten, R. A., Hoffman, S., and Klinman, D. M. (1996). Induction of neonatal tolerance by plasmid DNA vaccination of mice. J. Clin. Invest. 98:2700–2705.
Mossman, S., Bex, F., Berglund, P., Arthos, J., O’Neil, S. P., Riley, D., Maul, D. H., Bruck, C., Momin, P., Burny, A., Fultz, P. N., Mullins, J. I., Liljestrom, P., and Hoover, E. A. (1996). Protection against lethal SIVsmmPBj14 disease by a recombinant Semliki Forest virus gp160 vaccine and by gp120 subunit vaccine. J. Virol. 70:1953–1960.
Nichols, W. W., Ledwith, B. J., Manam, S. V., and Troilo, P. J. (1995). Potential DNA vaccine integration into host cell genome. Ann. N. Y. Acad. Sci. 772:30–39.
Nilsson, M., von Bonsdorff, C. H., Weclewicz, K., Cohen, J., and Svensson, L. (1998). Assembly of viroplasm and virus-like particles of rotavirus by a Semliki Forest virus replicon. Virology. 242:255–265.
Notka, F., Stahl-Hennig, C., Dittmer, U., Wolf, H., and Wagner, R. (1999). Construction and characterization of recombinant VLPs and Semliki Forest virus live vectors for comparative evaluation in the SHIV monkey model. Biol. Chem. 380:341–352.
Ohno, K., Sawai, K., Iijima, Y., Levin, B., and Meruelo, D. (1997). Cell-specific targeting of Sindbis virus vectors displaying IgG-binding domains of protein A. Nat. Biotechnol. 15:763–767.
Olivo, P. D., Collins, P. L., Peeples, M. E., and Schlesinger, S. (1998). Detection and quantitation of human respiratory syncytial virus (RSV) using minigenome cDNA and a Sindbis virus replicon: A prototype assay for negative-strand RNA viruses. Virology. 251:198–205.
Olivo, P. D., Frolov, I., and Schlesinger, S. (1994). A cell line that expresses a reporter gene in response to infection by Sindbis virus: a prototype for detection of positive strand RNA viruses. Virology. 198:381–384.
Olkkonen, V. M., Liljestrom, P., Garoff, H., Simons, K., and Dotti, C. G. (1993). Expression of heterologous proteins in cultured rat hippocampal neurons using the Semliki Forest virus vector. J. Neurosci. Res. 35:445–451.
Olson, K. E., Carlson, J. O., and Beaty, B. J. (1992). Expression of the chloramphenicol acetyltransferase gene in Aedes albopictus (C6/36) cells using a non-infectious Sindbis virus expression vector. Insect Mol. Biol. 1:49–52.
Olson, K. E., Higgs, S., Gaines, P. J., Powers, A. M., Davis, B. S., Kamrud, K. I., Carlson, J. O., Blair, C. D., and Beaty, B. J. (1996). Genetically engineered resistance to Dengue-2 virus transmission in mosquitoes. Science. 272:884–886.
Olson, K. E., Higgs, S., Hahn, C. S., Rice, C. M., Carlson, J. O., and Beaty, B. J. (1994). The expression of chloramphenicol acetyltransferase in Aedes albopictus (C6/36) cells and Aedes triseriatus mosquitoes using a double subgenomic recombinant Sindbis virus. Insect Biochem. & Mol. Biol. 24:39–48.
Opstelten, D. J., Wallin, M., and Garoff, H. (1998). Moloney murine leukemia virus envelope protein subunits, gp70 and Pr15E, form a stable disulfide-linked complex. J. Virol. 72:6537–6545.
Osterhaus, A. D. M. E., van Baalen, C. A., Gruters, R. A., Schutten, M., Siebelink, C. H. J., Hulskotte, E. G. J., Tijhaar, E. J., Randall, R. E. R., van Amerongen, G., Fleuchaus, A., Erfle, V., and Sutter, G. (1999). Vaccination with Rev and Tat against AIDS. Vaccine. 17:2713–2714.
Owe-Larsson, B., Berglund, M. M., Kristensson, K., Garoff, H., Larhammar, D., Brodin, L., and Low, P. (1999). Perturbation of the synaptic release machinery in hippocampal neurons by overexpression of SNAP-25 with the Semliki Forest virus vector. Eur. J. Neurosci. 11:1981–1987.
Paul, N. L., Marsh, M., McKeating, J. A., Schulz, T. F., Liljestrom, P., Garoff, H., and Weiss, R. A. (1993). Expression of HIV-1 envelope glycoproteins by Semliki Forest virus vectors. AIDS Res. Hum. Retroviruses. 9:963–970.
Polo, J. M., Belli, B. A., Driver, D. A., Frolov, I., Sherrill, S., Hariharan, M. J., Townsend, K., Perri, S., Mento, S. J., Jolly, D. J., Chang, S. M. W., Schlesinger, S., and Dubensky, T. W. Jr. (1999). Stable alphavirus packaging cells lines for Sindbis virus and Semliki Forest virus-derived vectors. Proc. Natl. Acad. Sci. USA. 96:4598–4603.
Powers, A. M., Olson, K. E., Higgs, S., Carlson, J. O., and Beaty, B. J. (1994). Intracellular immunization of mosquito cells to LaCrosse virus using a recombinant Sindbis virus vector. Virus Res. 32:57–67.
Pugachev, K. V., Mason, P. W., and Frey, T. K. (1995). Sindbis vectors suppress secretion of subviral particles of Japanese encephalitis virus from mammalian cells infected with SIN-JEV recombinants. Virology. 209:155–166.
Pugachev, K. V., Mason, P. W., Shope, R. E., and Frey, T. K. (1995). Double-subgenomic Sindbis virus recombinants expressing immunogenic proteins of Japanese encephalitis virus induce significant protection in mice against lethal JEV infection. Virology. 212:587–594.
Pushko, P., Parker, M., Ludwig, G. V., Davis, N. L., Johnston, R. E., and Smith, J. F. (1997). Replicon-helper systems from attenuated Venezuelan equine encephalitis virus — Expression of heterologous genes in vitro and immunization against heterologous pathogens in vivo. Virology. 239:389–401.
Raju, R. and Huang, H. V. (1991). Analysis of Sindbis virus promoter recognition in vivo, using novel vectors with two subgenomic mRNA promoters. J. Virol. 65:2501–2510.
Raju, R., Subramaniam, S. V., and Haijou, M. (1995). Genesis of Sindbis virus by in vivo recombination of nonreplicative RNA precursors. J. Virol. 69:7391–7401.
Rayms-Keller, A., Powers, A. M., Higgs, S., Olson, K. E., Kamrud, K. I., Carlson, J. O., and Beaty, B. J. (1995). Replication and expression of a recombinant Sindbis virus in mosquitoes. Insect Mol. Biol. 4:245–251.
Rice, C. M., Levis, R., Strauss, J. H., and Huang, H. V. (1987). Production of infectious RNA transcripts from Sindbis virus cDNA clones: map** of lethal mutations, rescue of a temperature-sensitive marker, and in vitro mutagenesis to generate defined mutants. J. Virol. 61:3809–3819.
Rolls, M. M., Haglund, K., and Rose, J. K. (1996). Expression of additional genes in a vector derived from a minimal RNA virus. Virology. 218:406–411.
Rolls, M. M., Webster, P., Balba, N. H., and Rose, J. K. (1994). Novel infectious particles generated by expression of the vesicular stomatitis virus glycoprotein from a self-replicating RNA. Cell. 79:497–506.
Ryan, M. D. and Drew, J. (1994). Foot-and-mouth disease virus 2A oligopeptide mediated cleavage of an artificial polyprotein. EMBO J. 13:928–933.
Ryan, M. D., King, A. M. Q., and Thomas, G. P. (1991). Cleavage of foot-and-mouth disease virus polyprotein is mediated by residues located within a 19 amino acid sequence. J. Gen. Virol. 72:2727–2732.
Salminen, A., Wahlberg, J. M., Lobigs, M., Liljeström, P., and Garoff, H. (1992). Membrane fusion process of Semliki Forest virus II: Cleavage dependent reorganization of the spike protein complex controls virus entry. J. Cell Biol. 116:349–357.
Sammin, D. J., Butler, D., Atkins, G. J., and Sheahan, B. J. (1999). Cell death mechanisms in the olfactory bulb of rats infected intranasally with Semliki Forest virus. Neuropathology and Applied Neurobiology. 25:236–243.
Sawai, K., Ikeda, H., Ishizu, A., and Meruelo, D. (1999). Reducing cytotoxicity induced by Sindbis viral vectors. Mol. Genet. Metabol. 67:36–42.
Sawai, K. and Meruelo, D. (1998). Cell-specific transfection of choriocarcinoma cells by using Sindbis virus hCG expressing chimeric vector. Biochem. Biophys. Res. Commun. 248:315–323.
Sawai, K., Ohno, K., Ijima, Y., Levin, B., and Meruelo, D. (1998). A novel method of cell-specific mRNA transfection. Mol. Genet. & Metabol. 64:44–51.
Scallan, M. F., Allsopp, T. E., and Fazakerley, J. K. (1997). bcl-2 acts early to restrict Semliki Forest virus replication and delays virus-induced programmed cell death. J. Virol. 71:1583–1590.
Scheer, A., Björklöf, K., Cotecchia, S., and Lundström, K. (1999). Expression of the alpha(1 b)-adrenergic receptor and G protein subunits in mammalian cell lines using Semliki Forest virus expression system. J. Rec. Signal Transd. Res. 19:369–378.
Schlaeger, E. J. and Lundström, K. (1998). Effect of temperature on recombinant protein expression in Semliki Forest virus infected mammalian cell lines growing in serum-free suspension cultures. Cytotechnol. 28:205–211.
Schlesinger, S. and Weiss, B. G. (1994). Recombination between Sindbis virus RNAs. Archiv. Virol. 9:213–220.
Seabaugh, R. C., Olson, K. E., Higgs, S., Carlson, J. O., and Beaty, B. J. (1998). Development of a chimeric Sindbis virus with enhanced per Os infection of Aedes aegypti. Virology. 243:99–112.
Simons, M., Tienari, P. J., Dotti, C. G., and Beyreuther, K. (1995). Two-dimensional gel map** of the processing of the human amyloid precursor protein in rat hippocampal neurons. FEBS Letters. 368:363–366.
Sjöberg, E. M. and Garoff, H. (1996). The translation-enhancing region of the Semliki Forest virus subgenome is only functional in the virus-infected cell. J. Gen. Virol. 77:1323–1327.
Sjöberg, E. M., Suomalainen, M., and Garoff, H. (1994). A significantly improved Semliki Forest virus expression system based on translation enhancer segments from the viral capsid gene. Bio/Technology. 12:1127–1131.
Skoging, U. and Liljeström, P. (1998). Role of the C-terminal tryptophan residue for the structure-function of alphavirus capsid protein. J. Mol. Biol. 279:865–872.
Skoging, U., Vihinen, M., Nilsson, L., and Liljeström, P. (1996). Aromatic interactions define the binding of the alphavirus spike to its nucleocapsid. Structure. 4:519–529.
Smerdou, C. and Liljeström, P. (1999). Two-helper RNA system for production of recombinant Semliki forest virus particles. J. Virol. 73:1092–1098.
Smith, S. M., Maldarelli, F., and Jeang, K. T. (1997). Efficient expression by an alphavirus replicon of a functional ribozyme targeted to human immunodeficiency virus type 1. J. Virol. 71:9713–9721.
Strauss, J. H. and Strauss, E. G. (1994). The alphaviruses: Gene expression, replication, and evolution. Microbiol. Revs. 58:491–562.
Suomalainen, M., Liljeström, P., and Garoff, H. (1992). Spike protein-nucleocapsid interactions drive the budding of alphaviruses. J. Virol. 66:4737–4747.
Torresi, J., Li, F., Locarnini, S. A., and Anderson, D. A. (1999). Only the non-glycosylated fraction of hepatitis E virus capsid (open reading frame 2) protein is stable in mammalian cells. J. Gen. Virol. 80:1185–1188.
Torresi, J., Meanger, J., Lambert, P., Li, F., Locarnini, S. A., and Anderson, D. A. (1997). High level expression of the capsid protein of hepatitis E virus in diverse eukaryotic cells using the Semliki Forest virus replicon. J. Virol. Meth. 69:81–91.
Tsuji, M., Bergmann, C. C., Takita-Sonoda, Y., Murata, K., Rodrigues, E. G., Nussenzweig, R. S., and Zavala, F. (1998). Recombinant Sindbis viruses expressing a cytotoxic T-lymphocyte epitope of a malaria parasite or of influenza virus elicit protection against the corresponding pathogen in mice. J. Virol. 72:6907–6910.
Tubulekas, I. and Liljeström, P. (1998). Suppressors of cleavage-site mutations in the p62 envelope protein of Semliki Forest virus reveal dynamics in spike structure function. J. Virol. 72:2825–2831.
Ulmanen, I., Peränen, J., Tenhunen, J., Tilgmann, C., Karhunen, T., Panula, P., Bernasconi, L., Aubry, J. P., and Lundström, K. (1997). Expression and intracellular localization of catechol O-methyltransferase in transfected mammalian cells. Eur. J. Biochem. 243:452–459.
Verrier, F. C., Chameau, P., Altmeyer, R., Laurent, S., Borman, A. M., and Girard, M. (1997). Antibodies to several conformation-dependent epitopes of gpl20/gp41 inhibit CCR-5-dependent cell-to-cell fusion mediated by the native envelope glycoprotein of a primary macrophage-tropic H1V-1 isolate. Proc. Natl. Acad. Sci. USA. 94:9326–9331.
Wahlfors, J. J. and Morgan, R. A. (1999). Production of minigen-containing retroviral vectors using an alphavirus/retrovirus hybrid vector system. Hum. Gene Ther. 10:1197–1206.
Wahlfors, J. J., Xanthopoulos, K. G., and Morgan, R. A. (1997). Semliki Forest virus-mediated production of retroviral vector RNA in retroviral packaging cells. Hum. Gene Ther. 8:2031–2041.
Weiss, B., Rosenthal, R., and Schlesinger, S. (1980). Establishment and maintenance of persistent infection by Sindbis virus in BHK cells. J. Virol. 33:463–474.
Weiss, B. G. and Schlesinger, S. (1991). Recombination between Sindbis virus RNAs. J. Virol. 65:4017–4025.
White, C. L., Thomson, M., and Dimmock, N. J. (1998). Deletion analysis of a defective interfering Semliki Forest virus RNA genome defines a region in the nsP2 sequence that is required for efficient packaging of the genome into virus particles. J. Virol. 72:4320–4326.
Wolff, J. A., Ludtke, J. J., Acsadi, G., Williams, P., and Jani, A. (1992). Long-term persistence of plasmid DNA and foreign gene expression in mouse muscle. Hum. Mol. Genet. 1:363–369.
**ong, C., Levis, R., Shen, P., Schlesinger, S., Rice, C. M., and Huang, H. V. (1989). Sindbis virus: an efficient, broad host range vector for gene expression in animal cells. Science. 243:1188–1191.
Yadani, F. Z., Kohl, A., Prehaud, C., Billecocq, A., and Bouloy, M. (1999). The carboxy-terminal acidic domain of Rift Valley fever virus NSs protein is essential for the formation of filamentous structures but not for the nuclear localization of the protein. J. Virol. 73:5018–5025.
Ying, H., Zaks, T. Z., Wang, R. F., Irvine, K. R., Kammula, U. S., Marincola, F. M., Leitner, W. W., and Restifo, N. P. (1999). Cancer therapy using a self-replicating RNA vaccine. Nat. Med. 5:823–827.
Zhang, J., Asselin-Paturel, C., Bex, F., Bernard, J., Chehimi, J., Willems, F., Caignard, A., Berglund, P., Liljeström, P., Burny, A., and Chouaib, S. (1997). Cloning of human 11-12 p40 and p35 DNA into the Semliki Forest virus vector: expression of 11-12 in human tumor cells. Gene Ther. 4:367–374.
Zhao, H., Lindqvist, B., Garoff, H., von Bonsdorff, C. H., and Liljeström, P. (1994). A tyrosine-based motif in the cytoplasmic domain of the alphavirus envelope protein is essential for budding. EMBO J. 13:4204–4211.
Zhou, X., Berglund, P., Rhodes, G., Parker, S. E., Jondal, M., and Liljeström, P. (1994). Self-replicating Semliki Forest virus RNA as recombinant vaccine. Vaccine. 12:1510–1514.
Zhou, X., Berglund, P., Zhao, H., Liljeström, P., and Jondal, M. (1995). Generation of cytotoxic and humoral immune responses by nonreplicative recombinant Semliki Forest virus. Proc. Natl. Acad. Sci. USA. 92:3009–3013.
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Smerdou, C., Liljeström, P. (2000). Alphavirus Vectors: Highly Efficient Systems for Transient Gene Expression. In: Al-Rubeai, M. (eds) Cell Engineering. Cell Engineering, vol 2. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-4315-8_7
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