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Journal of Virology, March 2008, p. 2358-2366, Vol. 82, No. 5
0022-538X/08/$08.00+0     doi:10.1128/JVI.01931-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Stabilization of TM Trimer Interactions during Activation of Moloney Murine Leukemia Virus Env{triangledown}

Mathilda Sjöberg, Birgitta Lindqvist, and Henrik Garoff*

Department of Biosciences and Nutrition, Karolinska Institute, S-141 57 Huddinge, Sweden

Received 4 September 2007/ Accepted 12 December 2007

The transmembrane subunit (TM) of the trimeric retrovirus Env complex is thought to direct virus-cell membrane fusion by refolding into a cell membrane-interacting, extended form that subsequently folds back on itself into a very stable trimer of hairpin-like TM polypeptides. However, so far there is only limited evidence for the formation of a stable TM trimer during Env activation. Here we have studied the oligomer composition and stability of an intermediate and the fully activated form of Moloney murine leukemia virus (Mo-MLV) Env. Activation of Mo-MLV Env is controlled by isomerization of its intersubunit disulfide. This results in surface subunit (SU) dissociation and TM refolding. If activation is done in the presence of an alkylator, this will modify the isomerization-active thiol in the SU of Env and arrest Env at an intermediate stage, the isomerization-arrested state (IAS) of its activation pathway. We generated IAS and fully activated Envs in vitro and in vivo and studied their states of oligomerization by two-dimensional blue native polyacrylamide gel electrophoresis (PAGE) and nonreducing sodium dodecyl sulfate (SDS)-PAGE. The IAS Env was composed of trimers of SU-TM complexes, whereas the activated Env consisted of SU monomers and TM trimers. When the oligomers were subjected to mild SDS treatment the TM trimer was found to be 3.5 times more resistant than the IAS oligomer. Thus, this demonstrates that a structural conversion of TM takes place during activation, which results in the formation of a stable TM trimer.

* Corresponding author. Mailing address: Department of Biosciences and Nutrition, Karolinska Institute, S-141 57 Huddinge, Sweden. Phone: 46-8-6089125. Fax: 46-8-7745538. E-mail: henrik.garoff{at}cbt.ki.se

{triangledown} Published ahead of print on 19 December 2007.

Journal of Virology, March 2008, p. 2358-2366, Vol. 82, No. 5
0022-538X/08/$08.00+0     doi:10.1128/JVI.01931-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Cote, M., Zheng, Y.-M., Liu, S.-L. (2009). Receptor Binding and Low pH Coactivate Oncogenic Retrovirus Envelope-Mediated Fusion. J. Virol. 83: 11447-11455 [Abstract] [Full Text]  
  • Lamb, D., Mirsaliotis, A., Kelly, S. M., Brighty, D. W. (2009). Basic Residues Are Critical to the Activity of Peptide Inhibitors of Human T Cell Leukemia Virus Type 1 Entry. J. Biol. Chem. 284: 6575-6584 [Abstract] [Full Text]  


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