Journal of General Virology, Vol 78, 3207-3215, Copyright © 1997 by Society for General Microbiology

ARTICLES

Isolation of an avirulent mutant of Sendai virus with two amino acid mutations from a highly virulent field strain through adaptation to LLC- MK2 cells

M Itoh, Y Isegawa, H Hotta and M Homma
Department of Microbiology, Kobe University School of Medicine, Japan. masae@med.kobe-u.ac.jp

A field strain of Sendai virus (SeV) Ohita-M1 (M1) was isolated from an epidemic in an animal laboratory by passaging in mice. A mutant strain, Ohita-MVC11 (MVC11), was then obtained by passaging M1 in rhesus monkey (LLC-MK2) cells. MVC11 was adapted to LLC-MK2 cells and produced 20 times higher levels of infectious virus than M1. This increased production of infectious virus in LLC-MK2 cells was associated with enhanced viral gene expression. However, MVC11 could not replicate efficiently in mouse lung and was not lethal to mice even when inoculated at a titre of 8 x 10(5) cell-infecting units (CIU) per mouse. On the other hand, with an inoculum of only 4 x 10(1) CIU per mouse, corresponding to 1 LD50, M1 replicated well in mouse lung and was highly virulent to mice. Nucleotide and deduced amino acid sequence analyses of the entire genomes of M1 and MVC11 revealed that adaptation to LLC-MK2 cells and the attenuation of mouse pathogenicity of MVC11 were associated with only two amino acid substitutions; one on the C protein (Phe substituted by Ser at position 170) and the other on the RNA polymerase, the L protein (Glu substituted by Ala at position 2050).

This article has been cited by other articles:

				J. B. Boonyaratanakornkit, E. J. Bartlett, E. Amaro-Carambot, P. L. Collins, B. R. Murphy, and A. C. Schmidt The C Proteins of Human Parainfluenza Virus Type 1 (HPIV1) Control the Transcription of a Broad Array of Cellular Genes That Would Otherwise Respond to HPIV1 Infection J. Virol., February 15, 2009; 83(4): 1892 - 1910. [Abstract] [Full Text] [PDF]

				E. J. Bartlett, A.-M. Cruz, J. Esker, A. Castano, H. Schomacker, S. R. Surman, M. Hennessey, J. Boonyaratanakornkit, R. J. Pickles, P. L. Collins, et al. Human Parainfluenza Virus Type 1 C Proteins Are Nonessential Proteins That Inhibit the Host Interferon and Apoptotic Responses and Are Required for Efficient Replication in Nonhuman Primates J. Virol., September 15, 2008; 82(18): 8965 - 8977. [Abstract] [Full Text] [PDF]

				A. Kato, K. Kiyotani, T. Kubota, T. Yoshida, M. Tashiro, and Y. Nagai Importance of the Anti-Interferon Capacity of Sendai Virus C Protein for Pathogenicity in Mice J. Virol., April 1, 2007; 81(7): 3264 - 3271. [Abstract] [Full Text] [PDF]

				S. Duffy, P. E. Turner, and C. L. Burch Pleiotropic Costs of Niche Expansion in the RNA Bacteriophage {Phi}6 Genetics, February 1, 2006; 172(2): 751 - 757. [Abstract] [Full Text] [PDF]

				M. Wiegand, S. Bossow, and W. J. Neubert Sendai virus trailer RNA simultaneously blocks two apoptosis-inducing mechanisms in a cell type-dependent manner J. Gen. Virol., August 1, 2005; 86(8): 2305 - 2314. [Abstract] [Full Text] [PDF]

				M. D. Baron, A. C. Banyard, S. Parida, and T. Barrett The Plowright vaccine strain of Rinderpest virus has attenuating mutations in most genes J. Gen. Virol., April 1, 2005; 86(4): 1093 - 1101. [Abstract] [Full Text] [PDF]

				A. Kato, C. Cortese-Grogan, S. A. Moyer, F. Sugahara, T. Sakaguchi, T. Kubota, N. Otsuki, M. Kohase, M. Tashiro, and Y. Nagai Characterization of the Amino Acid Residues of Sendai Virus C Protein That Are Critically Involved in Its Interferon Antagonism and RNA Synthesis Down-Regulation J. Virol., July 15, 2004; 78(14): 7443 - 7454. [Abstract] [Full Text] [PDF]

				J. T. Newman, J. M. Riggs, S. R. Surman, J. M. McAuliffe, T. A. Mulaikal, P. L. Collins, B. R. Murphy, and M. H. Skiadopoulos Generation of Recombinant Human Parainfluenza Virus Type 1 Vaccine Candidates by Importation of Temperature-Sensitive and Attenuating Mutations from Heterologous Paramyxoviruses J. Virol., February 15, 2004; 78(4): 2017 - 2028. [Abstract] [Full Text] [PDF]

				K. Nemirov, A. Lundkvist, A. Vaheri, and A. Plyusnin Adaptation of Puumala Hantavirus to Cell Culture Is Associated with Point Mutations in the Coding Region of the L Segment and in the Noncoding Regions of the S Segment J. Virol., August 15, 2003; 77(16): 8793 - 8800. [Abstract] [Full Text] [PDF]

				L. Strahle, D. Garcin, P. Le Mercier, J. F. Schlaak, and D. Kolakofsky Sendai Virus Targets Inflammatory Responses, as Well as the Interferon-Induced Antiviral State, in a Multifaceted Manner J. Virol., July 15, 2003; 77(14): 7903 - 7913. [Abstract] [Full Text] [PDF]

				S. de Breyne, V. Simonet, T. Pelet, and J. Curran Identification of a cis-acting element required for shunt-mediated translational initiation of the Sendai virus Y proteins Nucleic Acids Res., January 15, 2003; 31(2): 608 - 618. [Abstract] [Full Text] [PDF]

				Y. Fujii, T. Sakaguchi, K. Kiyotani, C. Huang, N. Fukuhara, Y. Egi, and T. Yoshida Involvement of the Leader Sequence in Sendai Virus Pathogenesis Revealed by Recovery of a Pathogenic Field Isolate from cDNA J. Virol., July 29, 2002; 76(17): 8540 - 8547. [Abstract] [Full Text] [PDF]

				A. Kato, Y. Ohnishi, M. Hishiyama, M. Kohase, S. Saito, M. Tashiro, and Y. Nagai The Amino-Terminal Half of Sendai Virus C Protein Is Not Responsible for either Counteracting the Antiviral Action of Interferons or Down-Regulating Viral RNA Synthesis J. Virol., June 14, 2002; 76(14): 7114 - 7124. [Abstract] [Full Text] [PDF]

				D. Garcin, J. Curran, M. Itoh, and D. Kolakofsky Longer and Shorter Forms of Sendai Virus C Proteins Play Different Roles in Modulating the Cellular Antiviral Response J. Virol., August 1, 2001; 75(15): 6800 - 6807. [Abstract] [Full Text]

				D. Garcin, J. Curran, and D. Kolakofsky Sendai Virus C Proteins Must Interact Directly with Cellular Components To Interfere with Interferon Action J. Virol., October 1, 2000; 74(19): 8823 - 8830. [Abstract] [Full Text]

				R. M. Bush, C. B. Smith, N. J. Cox, and W. M. Fitch Effects of passage history and sampling bias on phylogenetic reconstruction of human influenza A evolution PNAS, June 20, 2000; 97(13): 6974 - 6980. [Abstract] [Full Text] [PDF]

				D. Garcin, P. Latorre, and D. Kolakofsky Sendai Virus C Proteins Counteract the Interferon-Mediated Induction of an Antiviral State J. Virol., August 1, 1999; 73(8): 6559 - 6565. [Abstract] [Full Text]

				P. Latorre, T. Cadd, M. Itoh, J. Curran, and D. Kolakofsky The Various Sendai Virus C Proteins Are Not Functionally Equivalent and Exert both Positive and Negative Effects on Viral RNA Accumulation during the Course of Infection J. Virol., July 1, 1998; 72(7): 5984 - 5993. [Abstract] [Full Text] [PDF]

				M. Itoh, H. Hotta, and M. Homma Increased Induction of Apoptosis by a Sendai Virus Mutant Is Associated with Attenuation of Mouse Pathogenicity J. Virol., April 1, 1998; 72(4): 2927 - 2934. [Abstract] [Full Text] [PDF]