The Journal of Experimental Medicine
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Published online 5 February 2001.
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© 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 Ciureaa, Lukas Hunzikera, Paul Klenermana, Hans Hengartnera, and Rolf M. Zinkernagela

a Institute for Experimental Immunology, University Hospital, CH-8091 Zürich, Switzerland
Department of Internal Medicine, University Hospital, B-West-5, Raemistrasse 100, CH-8091 Zürich, Switzerland.41-1-255-456741-1-255-1111

adrian.ciurea{at}dim.usz.ch

We have shown previously that neutralizing antibodies (nAbs) are important contributors to the long-term immune control of lymphocytic choriomeningitis virus infection, particularly if cytotoxic T cell responses are low or absent. Nevertheless, virus escape from the nAb response due to mutations within the surface glycoprotein gene may subsequently allow the virus to persist. Here we show that most of the antibody-escape viral mutants retain their immunogenicity. We present evidence that the failure of the infected host to mount effective humoral responses against emerging neutralization-escape mutants correlates with the rapid loss of CD4+ T cell responsiveness during the establishment of viral persistence. Similar mechanisms may contribute to the persistence of some human pathogens such as hepatitis B and C viruses, and human immunodeficiency virus.

Key Words: persistent infection • lymphocytic choriomeningitis virus • T helper cells • humoral responses • viral evasion

A. Ciurea and L. Hunziker contributed equally to this work.

P. Klenerman's present address is Nuffield Department of Medicine, John Radcliffe Hospital, Oxford OX3 9DU, UK.

Abbreviations used in this paper: GP, glycoprotein; LCMV, lymphocytic choriomeningitis virus; nAb, neutralizing Ab; tg, transgenic; VSV, vesicular stomatitis virus; VSV-IND, VSV Indiana; wt, wild-type.

© 2001 The Rockefeller University Press


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