Persistence of lymphocytic choriomeningitis virus at very low levels in immune mice

Persistence of lymphocytic choriomeningitis virus at very low levels in immune mice

Institute for Experimental Immunology, Department of Pathology, University Hospital, CH-8091 Zurich, Switzerland

Contributed by Rolf M. Zinkernagel

Abstract

Lymphocytic choriomeningitis virus (LCMV), strain WE, is a non-cytopathic RNA virus that is highly adapted to its natural host, the mouse. Acute infection of adult mice leads to generalized virus spread, followed by cytotoxic T lymphocyte-mediated virus clearance below the detection levels of conventional assays within 2–3 weeks. Indirect evidence had suggested that virus or viral antigen might persist in the immune mouse. Here we demonstrate LCMV-WE persistence at low levels after infection with 10² or 10⁶ plaque-forming units, shown as viral genome, viral antigen, and replicative virus using sensitive in vitro and in vivo assays. The finding that LCMV-WE persists in the face of apparently intact immune responses resembles the situation in some viral (hepatitis B and C, HIV) and bacterial (tuberculosis, leprosy) infections in humans; the results are relevant to the understanding not only of other murine and human persistent viral infections but also of protective immunological memory by “infection immunity.”

Footnotes

↵ * To whom reprint requests should be addressed at: Institute for Experimental Immunology, University Hospital Zurich, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland. E-mail: aciurea{at}pathol.unizh.ch.
↵ † A.C. and P.K. contributed equally to this work.
↵ ‡ Present address: Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, United Kingdom.
Abbreviations:

CTL,

cytotoxic T lymphocyte;

GP,

glycoprotein;

LCMV,

lymphocytic choriomeningitis virus;

nAb,

neutralizing antibody;

NP,

nucleoprotein;

pfu,

plaque-forming units;

RT-PCR,

reverse transcriptase–PCR