This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by O'Reilly, L.
Right arrow Articles by Roth, M. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by O'Reilly, L.
Right arrow Articles by Roth, M. J.

 Previous Article  |  Next Article 

Journal of Virology, January 2000, p. 899-913, Vol. 74, No. 2
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Second-Site Changes Affect Viability of Amphotropic/Ecotropic Chimeric Enveloped Murine Leukemia Viruses

Lucille O'Reilly and Monica J. Roth*

Department of Biochemistry, University of Medicine and Dentistry of New Jersey---Robert Wood Johnson Medical School, Piscataway, New Jersey 08854

Received 13 November 1998/Accepted 29 September 1999

Chimeras were previously generated between the ecotropic (Moloney-MuLV) and amphotropic (4070A) SU and TM proteins of murine leukemia virus (MuLV). After passage in D17 cells, three chimeras with junctions in the C terminus of SU (AE5, AE6, and AE7), showed improved kinetics of viral spreading, suggesting that they had adapted. Sequencing of the viruses derived from the D17 cell lines revealed second-site changes within the env gene. Changes were detected in the receptor binding domain, the proline-rich region, the C terminus of SU, and the ectodomain of TM. Second-site changes were subcloned into the parental DNA, singly and in combination, and tested for viability. All viruses had maintained their original cloned mutations and junctions. Reconstruction and passage of AE7 or AE6 virus with single point mutations recovered the additional second-site changes identified in the parental population. The AE5 isolate required changes in the VRA, the VRC, the VRB-hinge region, and the C terminus of SU for efficient infection. Passage of virus, including the parental 4070A, in D17 cells resulted in a predominant G100R mutation within the receptor binding domain. Viruses were subjected to titer determination in three cell types, NIH 3T3, canine D17, and 293T. AE6 viruses with changes in the proline-rich region initially adapted for growth on D17 cells could infect all cell types tested. AE6-based chimeras with additional mutations in the C terminus of SU could infect D17 and 293T cells. Infection of NIH 3T3 cells was dependent on the proline-rich mutation. AE7-based chimeras encoding L538Q and G100R were impaired in infecting NIH 3T3 and 293T cells.

* Corresponding author. Mailing address: Department of Biochemistry, University of Medicine and Dentistry of New Jersey---Robert Wood Johnson Medical School, 675 Hoes Ln., Piscataway, NJ 08854. Phone: (732) 235-5048. Fax: (732) 235-4783; E-mail: Roth{at}waksman.rutgers.edu.

Journal of Virology, January 2000, p. 899-913, Vol. 74, No. 2
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Argaw, T., Figueroa, M., Salomon, D. R., Wilson, C. A. (2008). Identification of Residues outside of the Receptor Binding Domain That Influence the Infectivity and Tropism of Porcine Endogenous Retrovirus. J. Virol. 82: 7483-7491 [Abstract] [Full Text]  
  • Duggal, N. K., Goo, L., King, S. R., Telesnitsky, A. (2007). Effects of Identity Minimization on Moloney Murine Leukemia Virus Template Recognition and Frequent Tertiary Template-Directed Insertions during Nonhomologous Recombination. J. Virol. 81: 12156-12168 [Abstract] [Full Text]  
  • Puglia, J., Wang, T., Smith-Snyder, C., Cote, M., Scher, M., Pelletier, J. N., John, S., Jonsson, C. B., Roth, M. J. (2006). Revealing Domain Structure through Linker-Scanning Analysis of the Murine Leukemia Virus (MuLV) RNase H and MuLV and Human Immunodeficiency Virus Type 1 Integrase Proteins. J. Virol. 80: 9497-9510 [Abstract] [Full Text]  
  • O'Reilly, L., Roth, M. J. (2003). G541R within the 4070A TM Protein Regulates Fusion in Murine Leukemia Viruses. J. Virol. 77: 12011-12021 [Abstract] [Full Text]  
  • Lu, C.-W., Roth, M. J. (2003). Role of the Mutation Q252R in Activating Membrane Fusion in the Murine Leukemia Virus Surface Envelope Protein. J. Virol. 77: 10841-10849 [Abstract] [Full Text]  
  • Barnett, A. L., Wensel, D. L., Li, W., Fass, D., Cunningham, J. M. (2003). Structure and Mechanism of a Coreceptor for Infection by a Pathogenic Feline Retrovirus. J. Virol. 77: 2717-2729 [Abstract] [Full Text]  
  • Lu, C.-W., O'Reilly, L., Roth, M. J. (2002). G100R Mutation within 4070A Murine Leukemia Virus Env Increases Virus Receptor Binding, Kinetics of Entry, and Viral Transduction Efficiency. J. Virol. 77: 739-743 [Abstract] [Full Text]  
  • Lavillette, D., Ruggieri, A., Boson, B., Maurice, M., Cosset, F.-L. (2002). Relationship between SU Subdomains That Regulate the Receptor-Mediated Transition from the Native (Fusion-Inhibited) to the Fusion-Active Conformation of the Murine Leukemia Virus Glycoprotein. J. Virol. 76: 9673-9685 [Abstract] [Full Text]  
  • Seamon, J. A., Jones, K. S., Miller, C., Roth, M. J. (2002). Inserting a Nuclear Targeting Signal into a Replication-Competent Moloney Murine Leukemia Virus Affects Viral Export and Is Not Sufficient for Cell Cycle-Independent Infection. J. Virol. 76: 8475-8484 [Abstract] [Full Text]  
  • Farrell, K. B., Ting, Y.-T., Eiden, M. V. (2002). Fusion-Defective Gibbon Ape Leukemia Virus Vectors Can Be Rescued by Homologous but Not Heterologous Soluble Envelope Proteins. J. Virol. 76: 4267-4274 [Abstract] [Full Text]  
  • Barnett, A. L., Cunningham, J. M. (2001). Receptor Binding Transforms the Surface Subunit of the Mammalian C-Type Retrovirus Envelope Protein from an Inhibitor to an Activator of Fusion. J. Virol. 75: 9096-9105 [Abstract] [Full Text]  
  • Lu, C.-W., Roth, M. J. (2001). Functional Characterization of the N Termini of Murine Leukemia Virus Envelope Proteins. J. Virol. 75: 4357-4366 [Abstract] [Full Text]  
  • Barnett, A. L., Davey, R. A., Cunningham, J. M. (2001). Modular organization of the Friend murine leukemia virus envelope protein underlies the mechanism of infection. Proc. Natl. Acad. Sci. USA 98: 4113-4118 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»