Antibodies are not essential for the resolution of primary cytomegalovirus infection but limit dissemination of recurrent virus

doi:10.1084/jem.179.5.1713

This Article

	Full Text (PDF, 565K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JEM
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Jonjic, S.
	Articles by Koszinowski, U. H.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Jonjic, S.
	Articles by Koszinowski, U. H.


Social Bookmarking

	What's this?

ARTICLES

Antibodies are not essential for the resolution of primary cytomegalovirus infection but limit dissemination of recurrent virus

S Jonjic, I Pavic, B Polic, I Crnkovic, P Lucin and UH Koszinowski
Department of Physiology and Immunology, Faculty of Medicine, University of Rijeka, Croatia.

Virus shedding from the epithelial cells of the serous acini of salivary glands is a major source for the horizontal transmission of cytomegalovirus. These cells are, different to other tissues, exempt from CD8 T lymphocyte control. CD4 T lymphocytes are essential to terminate the productive infection. Here, we prove that T-B cooperation and the production of antibodies are not required for this process. For the infection with murine cytomegalovirus, mutant mice were used which do not produce antibodies because of a disrupted membrane exon of the immunoglobulin mu chain gene. Also, in these mice the virus clearance from salivary glands is a function of CD4 T lymphocytes. However, these mice clear the virus and establish viral latency with a kinetics that is distinguishable from normal mice. Reactivation from virus latency is the only stage at which the absence of antibodies alters the phenotype of infection. In immunoglobulin-deficient mice, virus recurrence results in higher virus titers. The adoptive serum transfer proved that antibody is the limited factor that prevents virus dissemination in the immunodeficient host.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

This article has been cited by other articles:

Snyder, C. M., Loewendorf, A., Bonnett, E. L., Croft, M., Benedict, C. A., Hill, A. B. (2009). CD4+ T Cell Help Has an Epitope-Dependent Impact on CD8+ T Cell Memory Inflation during Murine Cytomegalovirus Infection. J. Immunol. 183: 3932-3941 [Abstract] [Full Text]
Busche, A., Marquardt, A., Bleich, A., Ghazal, P., Angulo, A., Messerle, M. (2009). The Mouse Cytomegalovirus Immediate-Early 1 Gene Is Not Required for Establishment of Latency or for Reactivation in the Lungs. J. Virol. 83: 4030-4038 [Abstract] [Full Text]
Crough, T., Khanna, R. (2009). Immunobiology of Human Cytomegalovirus: from Bench to Bedside. Clin. Microbiol. Rev. 22: 76-98 [Abstract] [Full Text]
Cekinovic, D., Golemac, M., Pugel, E. P., Tomac, J., Cicin-Sain, L., Slavuljica, I., Bradford, R., Misch, S., Winkler, T. H., Mach, M., Britt, W. J., Jonjic, S. (2008). Passive Immunization Reduces Murine Cytomegalovirus-Induced Brain Pathology in Newborn Mice. J. Virol. 82: 12172-12180 [Abstract] [Full Text]
Bantug, G. R. B., Cekinovic, D., Bradford, R., Koontz, T., Jonjic, S., Britt, W. J. (2008). CD8+ T Lymphocytes Control Murine Cytomegalovirus Replication in the Central Nervous System of Newborn Animals. J. Immunol. 181: 2111-2123 [Abstract] [Full Text]
Arens, R., Wang, P., Sidney, J., Loewendorf, A., Sette, A., Schoenberger, S. P., Peters, B., Benedict, C. A. (2008). Cutting Edge: Murine Cytomegalovirus Induces a Polyfunctional CD4 T Cell Response. J. Immunol. 180: 6472-6476 [Abstract] [Full Text]
Cicin-Sain, L., Bubic, I., Schnee, M., Ruzsics, Z., Mohr, C., Jonjic, S., Koszinowski, U. H. (2007). Targeted Deletion of Regions Rich in Immune-Evasive Genes from the Cytomegalovirus Genome as a Novel Vaccine Strategy. J. Virol. 81: 13825-13834 [Abstract] [Full Text]
Butler, N. S., Dandekar, A. A., Perlman, S. (2007). Antiviral Antibodies Are Necessary To Prevent Cytotoxic T-Lymphocyte Escape in Mice Infected with a Coronavirus. J. Virol. 81: 13291-13298 [Abstract] [Full Text]
Klenovsek, K., Weisel, F., Schneider, A., Appelt, U., Jonjic, S., Messerle, M., Bradel-Tretheway, B., Winkler, T. H., Mach, M. (2007). Protection from CMV infection in immunodeficient hosts by adoptive transfer of memory B cells. Blood 110: 3472-3479 [Abstract] [Full Text]
Lenac, T., Budt, M., Arapovic, J., Hasan, M., Zimmermann, A., Simic, H., Krmpotic, A., Messerle, M., Ruzsics, Z., Koszinowski, U. H., Hengel, H., Jonjic, S. (2006). The herpesviral Fc receptor fcr-1 down-regulates the NKG2D ligands MULT-1 and H60. JEM 203: 1843-1850 [Abstract] [Full Text]
Barton, E. S., Lutzke, M. L., Rochford, R., Virgin, H. W. IV (2005). Alpha/Beta Interferons Regulate Murine Gammaherpesvirus Latent Gene Expression and Reactivation from Latency. J. Virol. 79: 14149-14160 [Abstract] [Full Text]
Kano, Y., Inaoka, M., Shiohara, T. (2004). Association Between Anticonvulsant Hypersensitivity Syndrome and Human Herpesvirus 6 Reactivation and Hypogammaglobulinemia. Arch Dermatol 140: 183-188 [Abstract] [Full Text]
Yue, Y., Zhou, S. S., Barry, P. A. (2003). Antibody responses to rhesus cytomegalovirus glycoprotein B in naturally infected rhesus macaques. J. Gen. Virol. 84: 3371-3379 [Abstract] [Full Text]
Mpandi, M., Otten, L. A., Lavanchy, C., Acha-Orbea, H., Finke, D. (2003). Passive Immunization with Neutralizing Antibodies Interrupts the Mouse Mammary Tumor Virus Life Cycle. J. Virol. 77: 9369-9377 [Abstract] [Full Text]
Kaur, A., Kassis, N., Hale, C. L., Simon, M., Elliott, M., Gomez-Yafal, A., Lifson, J. D., Desrosiers, R. C., Wang, F., Barry, P., Mach, M., Johnson, R. P. (2003). Direct Relationship between Suppression of Virus-Specific Immunity and Emergence of Cytomegalovirus Disease in Simian AIDS. J. Virol. 77: 5749-5758 [Abstract] [Full Text]
Cavanaugh, V. J., Deng, Y., Birkenbach, M. P., Slater, J. S., Campbell, A. E. (2003). Vigorous Innate and Virus-Specific Cytotoxic T-Lymphocyte Responses to Murine Cytomegalovirus in the Submaxillary Salivary Gland. J. Virol. 77: 1703-1717 [Abstract] [Full Text]
van Dommelen, S. L. H., Tabarias, H. A., Smyth, M. J., Degli-Esposti, M. A. (2003). Activation of Natural Killer (NK) T Cells during Murine Cytomegalovirus Infection Enhances the Antiviral Response Mediated by NK Cells. J. Virol. 77: 1877-1884 [Abstract] [Full Text]
Finke, D., Luther, S. A., Acha-Orbea, H. (2003). The role of neutralizing antibodies for mouse mammary tumor virus transmission and mammary cancer development. Proc. Natl. Acad. Sci. USA 100: 199-204 [Abstract] [Full Text]
Atalay, R., Zimmermann, A., Wagner, M., Borst, E., Benz, C., Messerle, M., Hengel, H. (2002). Identification and Expression of Human Cytomegalovirus Transcription Units Coding for Two Distinct Fc{gamma} Receptor Homologs. J. Virol. 76: 8596-8608 [Abstract] [Full Text]
Morello, C. S., Ye, M., Spector, D. H. (2002). Development of a Vaccine against Murine Cytomegalovirus (MCMV), Consisting of Plasmid DNA and Formalin-Inactivated MCMV, That Provides Long-Term, Complete Protection against Viral Replication. J. Virol. 76: 4822-4835 [Abstract] [Full Text]
Kim, I.-J., Flano, E., Woodland, D. L., Blackman, M. A. (2002). Antibody-Mediated Control of Persistent {gamma}-Herpesvirus Infection. J. Immunol. 168: 3958-3964 [Abstract] [Full Text]
Sester, M., Sester, U., Gartner, B., Kubuschok, B., Girndt, M., Meyerhans, A., Kohler, H. (2002). Sustained High Frequencies of Specific CD4 T Cells Restricted to a Single Persistent Virus. J. Virol. 76: 3748-3755 [Abstract] [Full Text]
Tschen, S.-I., Bergmann, C. C., Ramakrishna, C., Morales, S., Atkinson, R., Stohlman, S. A. (2002). Recruitment Kinetics and Composition of Antibody-Secreting Cells Within the Central Nervous System Following Viral Encephalomyelitis. J. Immunol. 168: 2922-2929 [Abstract] [Full Text]
Ramakrishna, C., Stohlman, S. A., Atkinson, R. D., Shlomchik, M. J., Bergmann, C. C. (2002). Mechanisms of Central Nervous System Viral Persistence: the Critical Role of Antibody and B Cells. J. Immunol. 168: 1204-1211 [Abstract] [Full Text]
Bitmansour, A. D., Waldrop, S. L., Pitcher, C. J., Khatamzas, E., Kern, F., Maino, V. C., Picker, L. J. (2001). Clonotypic Structure of the Human CD4+ Memory T Cell Response to Cytomegalovirus. J. Immunol. 167: 1151-1163 [Abstract] [Full Text]
Bergmann, C. C., Ramakrishna, C., Kornacki, M., Stohlman, S. A. (2001). Impaired T Cell Immunity in B Cell-Deficient Mice Following Viral Central Nervous System Infection. J. Immunol. 167: 1575-1583 [Abstract] [Full Text]
Sanna, P. P., Burton, D. R. (2000). Role of Antibodies in Controlling Viral Disease: Lessons from Experiments of Nature and Gene Knockouts. J. Virol. 74: 9813-9817 [Full Text]
Krmpotic, A., Messerle, M., Crnkovic-Mertens, I., Polic, B., Jonjic, S., Koszinowski, U. H. (1999). The Immunoevasive Function Encoded by the Mouse Cytomegalovirus Gene m152 Protects the Virus against T Cell Control in Vivo. JEM 190: 1285-1296 [Abstract] [Full Text]
Kurz, S. K., Reddehase, M. J. (1999). Patchwork Pattern of Transcriptional Reactivation in the Lungs Indicates Sequential Checkpoints in the Transition from Murine Cytomegalovirus Latency to Recurrence. J. Virol. 73: 8612-8622 [Abstract] [Full Text]
Speckner, A., Glykofrydes, D., Ohlin, M., Mach, M. (1999). Antigenic domain 1 of human cytomegalovirus glycoprotein B induces a multitude of different antibodies which, when combined, results in incomplete virus neutralization. J. Gen. Virol. 80: 2183-2191 [Abstract] [Full Text]
Lin, M. T., Hinton, D. R., Marten, N. W., Bergmann, C. C., Stohlman, S. A. (1999). Antibody Prevents Virus Reactivation Within the Central Nervous System. J. Immunol. 162: 7358-7368 [Abstract] [Full Text]
Weck, K. E., Kim, S. S., Virgin, H. W. IV, Speck, S. H. (1999). B Cells Regulate Murine Gammaherpesvirus 68�Latency. J. Virol. 73: 4651-4661 [Abstract] [Full Text]
Klein, M., Schoppel, K., Amvrossiadis, N., Mach, M. (1999). Strain-Specific Neutralization of Human Cytomegalovirus Isolates by Human Sera. J. Virol. 73: 878-886 [Abstract] [Full Text]
Stevenson, P., Cardin, R., Christensen, J., Doherty, P. (1999). Immunological control of a murine gammaherpesvirus independent of CD8+ T cells. J. Gen. Virol. 80: 477-483 [Abstract]
Kurz, S. K., Rapp, M., Steffens, H.-P., Grzimek, N. K.�A., Schmalz, S., Reddehase, M. J. (1999). Focal Transcriptional Activity of Murine Cytomegalovirus during Latency in the Lungs. J. Virol. 73: 482-494 [Abstract] [Full Text]
Polic, B., Hengel, H., Krmpotic, A., Trgovcich, J., Pavic, I., Lucin, P., Jonjic, S., Koszinowski, U. H. (1998). Hierarchical and Redundant Lymphocyte Subset Control Precludes Cytomegalovirus Replication during Latent Infection. JEM 188: 1047-1054 [Abstract] [Full Text]
Presti, R. M., Pollock, J. L., Dal Canto, A. J., O'Guin, A. K., Virgin, H. W. IV (1998). Interferon {gamma} Regulates Acute and Latent Murine Cytomegalovirus Infection and Chronic Disease of the Great Vessels. JEM 188: 577-588 [Abstract] [Full Text]
Stewart, J. P., Usherwood, E. J., Ross, A., Dyson, H., Nash, T. (1998). Lung Epithelial Cells Are a Major Site of Murine Gammaherpesvirus Persistence. JEM 187: 1941-1951 [Abstract] [Full Text]
Stevenson, P. G., Doherty, P. C. (1998). Kinetic Analysis of the Specific Host Response to a Murine Gammaherpesvirus. J. Virol. 72: 943-949 [Abstract] [Full Text]
Crnkovic-Mertens, I., Messerle, M., Szepan, U., Koszinowski, U. H. (1998). Virus Attenuation after Deletion of the Cytomegalovirus Fc Receptor Gene Is Not due to Antibody Control. J. Virol. 72: 1377-1382 [Abstract] [Full Text]
MacDonald, M. R., Li, X.-Y., Stenberg, R. M., Campbell, A. E., Virgin, H. W. IV (1998). Mucosal and Parenteral Vaccination against Acute and Latent Murine Cytomegalovirus (MCMV) Infection by Using an Attenuated MCMV Mutant. J. Virol. 72: 442-451 [Abstract] [Full Text]