This Article Full Text Full Text (PDF) An erratum has been published Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tibbetts, S. A. Articles by Virgin, H. W. Search for Related Content PubMed PubMed Citation Articles by Tibbetts, S. A. Articles by Virgin, H. W., IV

Effective Vaccination against Long-Term Gammaherpesvirus Latency

Department of Pathology & Immunology and Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110,¹ Department of Microbiology & Immunology, Yerkes Regional Primate Center, Emory University, Atlanta, Georgia 30329²

Received 6 August 2002/ Accepted 5 November 2002

The fundamental question of whether a primed immune system is capable of preventing latent gammaherpesvirus infection remains unanswered. Recent studies showing that vaccination can reduce acute replication and short-term latency but cannot alter long-term latency further call into question the possibility of achieving sterilizing immunity against gammaherpesviruses. Using the murine gammaherpesvirus 68 (HV68) system, we demonstrate that it is possible to effectively vaccinate against long-term latency. By immunizing mice with a HV68 mutant virus that is deficient in its ability to reactivate from latency, we reduced latent infection of wild-type challenge virus to a level below the limit of detection. Establishment of latency was inhibited by vaccination regardless of whether mice were challenged intraperitoneally or intranasally. Passive transfer of antibody from vaccinated mice could partially reconstitute the effect, demonstrating that antibody is an important component of vaccination. These results demonstrate the potential of a memory immune response against gammaherpesviruses to alter long-term latency and suggest that limiting long-term latent infection in a clinically relevant situation is an attainable goal.

This article has been cited by other articles:

• Stapler, D., Lee, E. D., Selvaraj, S. A., Evans, A. G., Kean, L. S., Speck, S. H., Larsen, C. P., Gangappa, S. (2008). Expansion of Effector Memory TCR V{beta}4+CD8+ T Cells Is Associated with Latent Infection-Mediated Resistance to Transplantation Tolerance. J. Immunol. 180: 3190-3200 [Abstract] [Full Text]  
• Kayhan, B., Yager, E. J., Lanzer, K., Cookenham, T., Jia, Q., Wu, T.-T., Woodland, D. L., Sun, R., Blackman, M. A. (2007). A Replication-Deficient Murine {gamma}-Herpesvirus Blocked in Late Viral Gene Expression Can Establish Latency and Elicit Protective Cellular Immunity. J. Immunol. 179: 8392-8402 [Abstract] [Full Text]  
• Kim, I.-J., Burkum, C. E., Cookenham, T., Schwartzberg, P. L., Woodland, D. L., Blackman, M. A. (2007). Perturbation of B Cell Activation in SLAM-Associated Protein-Deficient Mice Is Associated with Changes in Gammaherpesvirus Latency Reservoirs. J. Immunol. 178: 1692-1701 [Abstract] [Full Text]  
• Moser, J. M., Farrell, M. L., Krug, L. T., Upton, J. W., Speck, S. H. (2006). A Gammaherpesvirus 68 Gene 50 Null Mutant Establishes Long-Term Latency in the Lung but Fails To Vaccinate against a Wild-Type Virus Challenge. J. Virol. 80: 1592-1598 [Abstract] [Full Text]  
• Tarakanova, V. L., Suarez, F., Tibbetts, S. A., Jacoby, M. A., Weck, K. E., Hess, J. L., Speck, S. H., Virgin, H. W. IV (2005). Murine Gammaherpesvirus 68 Infection Is Associated with Lymphoproliferative Disease and Lymphoma in BALB {beta}2 Microglobulin-Deficient Mice. J. Virol. 79: 14668-14679 [Abstract] [Full Text]  
• Obar, J. J., Donovan, D. C., Crist, S. G., Silvia, O., Stewart, J. P., Usherwood, E. J. (2004). T-Cell Responses to the M3 Immune Evasion Protein of Murid Gammaherpesvirus 68 Are Partially Protective and Induced with Lytic Antigen Kinetics. J. Virol. 78: 10829-10832 [Abstract] [Full Text]  
• Rickabaugh, T. M., Brown, H. J., Martinez-Guzman, D., Wu, T.-T., Tong, L., Yu, F., Cole, S., Sun, R. (2004). Generation of a Latency-Deficient Gammaherpesvirus That Is Protective against Secondary Infection. J. Virol. 78: 9215-9223 [Abstract] [Full Text]  
• Sparks-Thissen, R. L., Braaten, D. C., Kreher, S., Speck, S. H., Virgin, H. W. IV (2004). An Optimized CD4 T-Cell Response Can Control Productive and Latent Gammaherpesvirus Infection. J. Virol. 78: 6827-6835 [Abstract] [Full Text]  
• McClellan, J. S., Tibbetts, S. A., Gangappa, S., Brett, K. A., Virgin, H. W. IV (2004). Critical Role of CD4 T Cells in an Antibody-Independent Mechanism of Vaccination against Gammaherpesvirus Latency. J. Virol. 78: 6836-6845 [Abstract] [Full Text]  
• Fowler, P., Efstathiou, S. (2004). Vaccine potential of a murine gammaherpesvirus-68 mutant deficient for ORF73. J. Gen. Virol. 85: 609-613 [Abstract] [Full Text]  
• Andreansky, S., Liu, H., Adler, H., Koszinowski, U. H., Efstathiou, S., Doherty, P. C. (2004). The limits of protection by "memory" T cells in Ig-/- mice persistently infected with a {gamma}-herpesvirus. Proc. Natl. Acad. Sci. USA 101: 2017-2022 [Abstract] [Full Text]  
• Boname, J. M., Coleman, H. M., May, J. S., Stevenson, P. G. (2004). Protection against wild-type murine gammaherpesvirus-68 latency by a latency-deficient mutant. J. Gen. Virol. 85: 131-135 [Abstract] [Full Text]  
• Tibbetts, S. A., Loh, J., van Berkel, V., McClellan, J. S., Jacoby, M. A., Kapadia, S. B., Speck, S. H., Virgin, H. W. IV (2003). Establishment and Maintenance of Gammaherpesvirus Latency Are Independent of Infective Dose and Route of Infection. J. Virol. 77: 7696-7701 [Abstract] [Full Text]  
• van Dyk, L. F., Virgin, H. W. IV, Speck, S. H. (2003). Maintenance of Gammaherpesvirus Latency Requires Viral Cyclin in the Absence of B Lymphocytes. J. Virol. 77: 5118-5126 [Abstract] [Full Text]