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Journal of Virology, June 2004, p. 6322-6334, Vol. 78, No. 12
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.12.6322-6334.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Identification of a Protective CD4+ T-Cell Epitope in p15gag of Friend Murine Leukemia Virus and Role of the MA Protein Targeting the Plasma Membrane in Immunogenicity

Daisuke Sugahara, Sachiyo Tsuji-Kawahara,* and Masaaki Miyazawa

Department of Immunology, Kinki University School of Medicine, Osaka-Sayama, Osaka 589-8511, Japan

Received 15 October 2003/ Accepted 19 February 2004

Recent studies have demonstrated an essential role of Gag-specific CD4+ T-cell responses for viral control in individuals infected with human immunodeficiency virus type 1. However, little is known about epitope specificities and functional roles of the Gag-specific helper T-cell responses in terms of vaccine-induced protection against a pathogenic retroviral challenge. We have previously demonstrated that immunization with Friend murine leukemia virus (F-MuLV) Gag proteins protects mice against the fatal Friend retrovirus (FV) infection. We report here the structure of a protective T helper cell (Th) epitope, (I)VTWEAIAVDPPP, identified in the p15 (MA) region of F-MuLV Gag. In mice immunized with the Th epitope-harboring peptide or a vaccinia virus-expressed native full-length MA protein, FV-induced early splenomegaly regressed rapidly. In these mice, FV-infected cells were eliminated within 4 weeks and the production of virus-neutralizing antibodies was induced rapidly after FV challenge, resulting in strong protection against the virus infection. Interestingly, mice immunized with the whole MA mounted strong CD4+ T-cell responses to the identified Th epitope, whereas mice immunized with mutant MA proteins that were not bound to the plasma membrane failed to mount efficient CD4+ T-cell responses, despite the presence of the Th epitope. These mutant MA proteins also failed to induce strong protection against FV challenge. These data indicate the importance of the properly processible MA molecule for CD4+ T-cell priming and for the resultant induction of an effective immune response against retrovirus infections.

* Corresponding author. Mailing address: Department of Immunology, Kinki University School of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan. Phone and fax: 81-72-367-7660. E-mail: skawa{at}immunol.med.kindai.ac.jp.

Journal of Virology, June 2004, p. 6322-6334, Vol. 78, No. 12
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.12.6322-6334.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Takeda, E., Tsuji-Kawahara, S., Sakamoto, M., Langlois, M.-A., Neuberger, M. S., Rada, C., Miyazawa, M. (2008). Mouse APOBEC3 Restricts Friend Leukemia Virus Infection and Pathogenesis In Vivo. J. Virol. 82: 10998-11008 [Abstract] [Full Text]  
  • Kawabata, H., Niwa, A., Tsuji-Kawahara, S., Uenishi, H., Iwanami, N., Matsukuma, H., Abe, H., Tabata, N., Matsumura, H., Miyazawa, M. (2006). Peptide-induced immune protection of CD8+ T cell-deficient mice against Friend retrovirus-induced disease. Int Immunol 18: 183-198 [Abstract] [Full Text]  
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