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 McGettigan, J. P.
Right arrow Articles by Schnell, M. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by McGettigan, J. P.
Right arrow Articles by Schnell, M. J.

 Previous Article  |  Next Article 

Journal of Virology, September 2001, p. 8724-8732, Vol. 75, No. 18
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.18.8724-8732.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Expression and Immunogenicity of Human Immunodeficiency Virus Type 1 Gag Expressed by a Replication-Competent Rhabdovirus-Based Vaccine Vector

James P. McGettigan,1,2 Satyam Sarma,3,4 Jan M. Orenstein,5 Roger J. Pomerantz,1,3,4 and Matthias J. Schnell1,3,*

Dorrance H. Hamilton Laboratories, Center for Human Virology,1 and Departments of Biochemistry and Molecular Pharmacology,3 Microbiology and Immunology,2 and Medicine,4 Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, and George Washington University Medical Center, Washington, D.C. 200375

Received 4 April 2001/Accepted 18 June 2001

A replication-competent rhabdovirus-based vector expressing human immunodeficiency virus type 1 (HIV-1) Gag protein was characterized on human cell lines and analyzed for the induction of a cellular immune response in mice. We previously described a rabies virus (RV) vaccine strain-based vector expressing HIV-1 gp160. The recombinant RV was able to induce strong humoral and cellular immune responses against the HIV-1 envelope protein in mice (M. J. Schnell et al., Proc. Natl. Acad. Sci. USA 97:3544-3549, 2000; J. P. McGettigan et al., J. Virol. 75:4430-4434, 2001). Recent research suggests that the HIV-1 Gag protein is another important target for cell-mediated host immune defense. Here we show that HIV-1 Gag can efficiently be expressed by RV on both human and nonhuman cell lines. Infection of HeLa cells with recombinant RV expressing HIV-1 Gag resulted in efficient expression of HIV-1 precursor protein p55 as indicated by both immunostaining and Western blotting. Moreover, HIV-1 p24 antigen capture enzyme-linked immunosorbent assay and electron microscopy showed efficient release of HIV-1 virus-like particles in addition to bullet-shaped RV particles in the supernatants of the infected cells. To initially screen the immunogenicity of this new vaccine vector, BALB/c mice received a single vaccination with the recombinant RV expressing HIV-1 Gag. Immunized mice developed a vigorous CD8+ cytotoxic T-lymphocyte response against HIV-1 Gag. In addition, 26.8% of CD8+ T cells from mice immunized with RV expressing HIV-1 Gag produced gamma interferon after challenge with a recombinant vaccinia virus expressing HIV-1 Gag. These results further confirm and extend the potency of RV-based vectors as a potential HIV-1 vaccine.

* Corresponding author. Mailing address: 1020 Locust St., Suite 335, Philadelphia, PA 19107-6799. Phone: (215) 503-1260. Fax: (215) 923-1956. E-mail: matthias.schnell{at}mail.tju.edu.

Journal of Virology, September 2001, p. 8724-8732, Vol. 75, No. 18
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.18.8724-8732.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Wirblich, C., Tan, G. S., Papaneri, A., Godlewski, P. J., Orenstein, J. M., Harty, R. N., Schnell, M. J. (2008). PPEY Motif within the Rabies Virus (RV) Matrix Protein Is Essential for Efficient Virion Release and RV Pathogenicity. J. Virol. 82: 9730-9738 [Abstract] [Full Text]  
  • Bukreyev, A., Skiadopoulos, M. H., Murphy, B. R., Collins, P. L. (2006). Nonsegmented negative-strand viruses as vaccine vectors.. J. Virol. 80: 10293-10306 [Full Text]  
  • Plesa, G., McKenna, P. M., Schnell, M. J., Eisenlohr, L. C. (2006). Immunogenicity of cytopathic and noncytopathic viral vectors.. J. Virol. 80: 6259-6266 [Abstract] [Full Text]  
  • Wirblich, C., Bhattacharya, B., Roy, P. (2006). Nonstructural Protein 3 of Bluetongue Virus Assists Virus Release by Recruiting ESCRT-I Protein Tsg101. J. Virol. 80: 460-473 [Abstract] [Full Text]  
  • Faber, M., Lamirande, E. W., Roberts, A., Rice, A. B., Koprowski, H., Dietzschold, B., Schnell, M. J. (2005). A single immunization with a rhabdovirus-based vector expressing severe acute respiratory syndrome coronavirus (SARS-CoV) S protein results in the production of high levels of SARS-CoV-neutralizing antibodies. J. Gen. Virol. 86: 1435-1440 [Abstract] [Full Text]  
  • Faber, M., Pulmanausahakul, R., Nagao, K., Prosniak, M., Rice, A. B., Koprowski, H., Schnell, M. J., Dietzschold, B. (2004). Identification of viral genomic elements responsible for rabies virus neuroinvasiveness. Proc. Natl. Acad. Sci. USA 101: 16328-16332 [Abstract] [Full Text]  
  • Nakamichi, K., Inoue, S., Takasaki, T., Morimoto, K., Kurane, I. (2004). Rabies Virus Stimulates Nitric Oxide Production and CXC Chemokine Ligand 10 Expression in Macrophages through Activation of Extracellular Signal-Regulated Kinases 1 and 2. J. Virol. 78: 9376-9388 [Abstract] [Full Text]  
  • Irie, T., Licata, J. M., McGettigan, J. P., Schnell, M. J., Harty, R. N. (2004). Budding of PPxY-Containing Rhabdoviruses Is Not Dependent on Host Proteins TGS101 and VPS4A. J. Virol. 78: 2657-2665 [Abstract] [Full Text]  
  • McKenna, P. M., Pomerantz, R. J., Dietzschold, B., McGettigan, J. P., Schnell, M. J. (2003). Covalently Linked Human Immunodeficiency Virus Type 1 gp120/gp41 Is Stably Anchored in Rhabdovirus Particles and Exposes Critical Neutralizing Epitopes. J. Virol. 77: 12782-12794 [Abstract] [Full Text]  
  • McGettigan, J. P., Naper, K., Orenstein, J., Koser, M., McKenna, P. M., Schnell, M. J. (2003). Functional Human Immunodeficiency Virus Type 1 (HIV-1) Gag-Pol or HIV-1 Gag-Pol and Env Expressed from a Single Rhabdovirus-Based Vaccine Vector Genome. J. Virol. 77: 10889-10899 [Abstract] [Full Text]  
  • Harvey, T. J., Anraku, I., Linedale, R., Harrich, D., Mackenzie, J., Suhrbier, A., Khromykh, A. A. (2003). Kunjin Virus Replicon Vectors for Human Immunodeficiency Virus Vaccine Development. J. Virol. 77: 7796-7803 [Abstract] [Full Text]  
  • McGettigan, J. P., Pomerantz, R. J., Siler, C. A., McKenna, P. M., Foley, H. D., Dietzschold, B., Schnell, M. J. (2002). Second-Generation Rabies Virus-Based Vaccine Vectors Expressing Human Immunodeficiency Virus Type 1 Gag Have Greatly Reduced Pathogenicity but Are Highly Immunogenic. J. Virol. 77: 237-244 [Abstract] [Full Text]  
  • Storni, T., Lechner, F., Erdmann, I., Bachi, T., Jegerlehner, A., Dumrese, T., Kundig, T. M., Ruedl, C., Bachmann, M. F. (2002). Critical Role for Activation of Antigen-Presenting Cells in Priming of Cytotoxic T Cell Responses After Vaccination with Virus-Like Particles. J. Immunol. 168: 2880-2886 [Abstract] [Full Text]  
  • Faber, M., Pulmanausahakul, R., Hodawadekar, S. S., Spitsin, S., McGettigan, J. P., Schnell, M. J., Dietzschold, B. (2002). Overexpression of the Rabies Virus Glycoprotein Results in Enhancement of Apoptosis and Antiviral Immune Response. J. Virol. 76: 3374-3381 [Abstract] [Full Text]  
  • Foley, H. D., Otero, M., Orenstein, J. M., Pomerantz, R. J., Schnell, M. J. (2002). Rhabdovirus-Based Vectors with Human Immunodeficiency Virus Type 1 (HIV-1) Envelopes Display HIV-1-Like Tropism and Target Human Dendritic Cells. J. Virol. 76: 19-31 [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»