Impairment of CD4+ T Cell Responses during Chronic Virus Infection Prevents Neutralizing Antibody Responses against Virus Escape Mutants

doi:10.1084/jem.193.3.297

Published online 29 January 2001.

This Article

	Full Text
	Full Text (PDF, 169K)
	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 Ciurea, A.
	Articles by Zinkernagel, R. M.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Ciurea, A.
	Articles by Zinkernagel, R. M.


Social Bookmarking

	What's this?

© The Rockefeller University Press, 0022-1007/2001/2/297/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 3, February 5, 2001 297-306

Original Article

Impairment of CD4⁺ T Cell Responses during Chronic Virus Infection Prevents Neutralizing Antibody Responses against Virus Escape Mutants

Adrian Ciurea^a, Lukas Hunziker^a, Paul Klenerman^a, Hans Hengartner^a, and Rolf M. Zinkernagel^a
^a Institute for Experimental Immunology, University Hospital, CH-8091 Zürich, Switzerland

Correspondence to: Adrian Ciurea, Department of Internal Medicine, University Hospital, B-West-5, Raemistrasse 100, CH-8091 Zürich, Switzerland. Tel:41-1-255-1111 Fax:41-1-255-4567 E-mail:adrian.ciurea{at}dim.usz.ch.

We have shown previously that neutralizing antibodies (nAbs)are important contributors to the long-term immune control oflymphocytic choriomeningitis virus infection, particularly ifcytotoxic T cell responses are low or absent. Nevertheless,virus escape from the nAb response due to mutations within thesurface glycoprotein gene may subsequently allow the virus topersist. Here we show that most of the antibody-escape viralmutants retain their immunogenicity. We present evidence thatthe failure of the infected host to mount effective humoralresponses against emerging neutralization-escape mutants correlateswith the rapid loss of CD4⁺ T cell responsiveness during theestablishment of viral persistence. Similar mechanisms may contributeto the persistence of some human pathogens such as hepatitisB and C viruses, and human immunodeficiency virus.

Key Words: persistent infection, lymphocytic choriomeningitis virus, Thelper cells, humoral responses, viral evasion

Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

Li, H., Chien, P. C. Jr., Tuen, M., Visciano, M. L., Cohen, S., Blais, S., Xu, C.-F., Zhang, H.-T., Hioe, C. E. (2008). Identification of an N-Linked Glycosylation in the C4 Region of HIV-1 Envelope gp120 That Is Critical for Recognition of Neighboring CD4 T Cell Epitopes. J. Immunol. 180: 4011-4021 [Abstract] [Full Text]
Eschli, B., Zellweger, R. M., Wepf, A., Lang, K. S., Quirin, K., Weber, J., Zinkernagel, R. M., Hengartner, H. (2007). Early Antibodies Specific for the Neutralizing Epitope on the Receptor Binding Subunit of the Lymphocytic Choriomeningitis Virus Glycoprotein Fail To Neutralize the Virus. J. Virol. 81: 11650-11657 [Abstract] [Full Text]
Zimmermann, V. S., Casati, A., Schiering, C., Caserta, S., Hess Michelini, R., Basso, V., Mondino, A. (2007). Tumors Hamper the Immunogenic Competence of CD4+ T Cell-Directed Dendritic Cell Vaccination. J. Immunol. 179: 2899-2909 [Abstract] [Full Text]
Charalambous, A., Oks, M., Nchinda, G., Yamazaki, S., Steinman, R. M. (2006). Dendritic Cell Targeting of Survivin Protein in a Xenogeneic Form Elicits Strong CD4+ T Cell Immunity to Mouse Survivin. J. Immunol. 177: 8410-8421 [Abstract] [Full Text]
Bertoletti, A., Gehring, A. J. (2006). The immune response during hepatitis B virus infection. J. Gen. Virol. 87: 1439-1449 [Abstract] [Full Text]
Brooks, D. G., Teyton, L., Oldstone, M. B. A., McGavern, D. B. (2005). Intrinsic Functional Dysregulation of CD4 T Cells Occurs Rapidly following Persistent Viral Infection. J. Virol. 79: 10514-10527 [Abstract] [Full Text]
Orozco, J. J., Carter, J. J., Koutsky, L. A., Galloway, D. A. (2005). Humoral Immune Response Recognizes a Complex Set of Epitopes on Human Papillomavirus Type 6 L1 Capsomers. J. Virol. 79: 9503-9514 [Abstract] [Full Text]
Mwangi, W., Brown, W. C., Splitter, G. A., Zhuang, Y., Kegerreis, K., Palmer, G. H. (2005). Enhancement of antigen acquisition by dendritic cells and MHC class II-restricted epitope presentation to CD4+ T cells using VP22 DNA vaccine vectors that promote intercellular spreading following initial transfection. J. Leukoc. Biol. 78: 401-411 [Abstract] [Full Text]
Benigni, F., Zimmermann, V. S., Hugues, S., Caserta, S., Basso, V., Rivino, L., Ingulli, E., Malherbe, L., Glaichenhaus, N., Mondino, A. (2005). Phenotype and Homing of CD4 Tumor-Specific T Cells Is Modulated by Tumor Bulk. J. Immunol. 175: 739-748 [Abstract] [Full Text]
Chang, J. J., Wightman, F., Bartholomeusz, A., Ayres, A., Kent, S. J., Sasadeusz, J., Lewin, S. R. (2005). Reduced Hepatitis B Virus (HBV)-Specific CD4+ T-Cell Responses in Human Immunodeficiency Virus Type 1-HBV-Coinfected Individuals Receiving HBV-Active Antiretroviral Therapy. J. Virol. 79: 3038-3051 [Abstract] [Full Text]
Chien, P. C. Jr., Cohen, S., Tuen, M., Arthos, J., Chen, P.-d., Patel, S., Hioe, C. E. (2004). Human Immunodeficiency Virus Type 1 Evades T-Helper Responses by Exploiting Antibodies That Suppress Antigen Processing. J. Virol. 78: 7645-7652 [Abstract] [Full Text]
Shoukry, N. H., Sidney, J., Sette, A., Walker, C. M. (2004). Conserved Hierarchy of Helper T Cell Responses in a Chimpanzee during Primary and Secondary Hepatitis C Virus Infections. J. Immunol. 172: 483-492 [Abstract] [Full Text]
Day, C. L., Walker, B. D. (2003). Progress in Defining CD4 Helper Cell Responses in Chronic Viral Infections. JEM 198: 1773-1777 [Full Text]
Hunziker, L., Ciurea, A., Recher, M., Hengartner, H., Zinkernagel, R. M. (2003). Public versus personal serotypes of a viral quasispecies. Proc. Natl. Acad. Sci. USA 100: 6015-6020 [Abstract] [Full Text]
Lopez-Bueno, A., Mateu, M. G., Almendral, J. M. (2003). High Mutant Frequency in Populations of a DNA Virus Allows Evasion from Antibody Therapy in an Immunodeficient Host. J. Virol. 77: 2701-2708 [Abstract] [Full Text]
Day, C. L., Lauer, G. M., Robbins, G. K., McGovern, B., Wurcel, A. G., Gandhi, R. T., Chung, R. T., Walker, B. D. (2002). Broad Specificity of Virus-Specific CD4+ T-Helper-Cell Responses in Resolved Hepatitis C Virus Infection. J. Virol. 76: 12584-12595 [Abstract] [Full Text]
Hunziker, L., Recher, M., Ciurea, A., Martinic, M. M.A., Odermatt, B., Hengartner, H., Zinkernagel, R. M. (2002). Antagonistic Variant Virus Prevents Wild-type Virus-induced Lethal Immunopathology. JEM 196: 1039-1046 [Abstract] [Full Text]
Venturini, S., Mosier, D. E., Burton, D. R., Poignard, P. (2002). Characterization of Human Immunodeficiency Virus Type 1 (HIV-1) Gag- and Gag Peptide-Specific CD4+ T-Cell Clones from an HIV-1-Seronegative Donor following In Vitro Immunization. J. Virol. 76: 6987-6999 [Abstract] [Full Text]
Schuurhuis, D. H., Ioan-Facsinay, A., Nagelkerken, B., van Schip, J. J., Sedlik, C., Melief, C. J. M., Verbeek, J. S., Ossendorp, F. (2002). Antigen-Antibody Immune Complexes Empower Dendritic Cells to Efficiently Prime Specific CD8+ CTL Responses In Vivo. J. Immunol. 168: 2240-2246 [Abstract] [Full Text]
Ou, R., Zhou, S., Huang, L., Moskophidis, D. (2001). Critical Role for Alpha/Beta and Gamma Interferons in Persistence of Lymphocytic Choriomeningitis Virus by Clonal Exhaustion of Cytotoxic T Cells. J. Virol. 75: 8407-8423 [Abstract] [Full Text]