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Public versus personal serotypes of a viral quasispecies
Lukas Hunziker1, Adrian Ciurea, Mike Recher
1Institute for Experimental Immunology, University Hospital, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland. lhunziker@uhbs.ch
Abstract:
Noncytopathic RNA viruses persist in their natural hosts at various levels as highly mutating quasispecies. They exhibit only one known serotype. In most inbred DBA2 mice infected with 2 x 10(4) or 2 x 10(6) plaque-forming units (pfu) of lymphocytic choriomeningitis virus (LCMV), the virus is transiently controlled below detectable levels measured with conventional assays (<1.7 pfu), but reemerges despite a common neutralizing Ab (nAb) response. Wild-type virus and cloned mutant viruses that had escaped polyclonal nAb responses in vivo induced nAb titers in new hosts that were usually cross-reactive; some sera were highly specific for certain mutants. The few mice that controlled LCMV infection for >170 days produced not only nAb against wild-type but also variably against many other mutants isolated from other mice with reemerging viremia. When DBA2 mice were immunized and boosted with 200 pfu of a LCMV mutant, the neutralizing Ab response was limited to the immunizing "personal" clone. Thus, in contrast to classical serotype-defined cytopathic viruses (e.g., polio viruses) that induce strictly non-cross-reactive nAb titers, LCMV, a noncytopathic RNA virus, represents a dynamic multiplicity of personal serological submutants. Together, these mutants form a generally recognized "public" serotype. These findings may help to explain aspects of human infections and Ab responses against hepatitis B virus, hepatitis C virus, and HIV.
Insights
Noncytopathic RNA viruses like lymphocytic choriomeningitis virus (LCMV) evade immune control through rapid mutation. Despite neutralizing antibody responses, LCMV persists by generating diverse viral variants, challenging traditional serotyping.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Noncytopathic RNA viruses, such as lymphocytic choriomeningitis virus (LCMV), persist in hosts as quasispecies.
- These viruses exhibit a single known serotype but can evade immune responses.
Purpose of the Study:
- To investigate the immune evasion strategies of LCMV in DBA2 mice.
- To characterize the neutralizing antibody (nAb) response to LCMV wild-type and mutant strains.
Main Methods:
- Infection of inbred DBA2 mice with varying doses of LCMV.
- Analysis of viral load, reemergence, and neutralizing antibody titers.
- Isolation and characterization of LCMV mutants escaping nAb responses.
Main Results:
- LCMV was transiently controlled but reemerged despite nAb responses.
- nAb titers induced by wild-type and mutant LCMV showed cross-reactivity, with some specificity for certain mutants.
- Immunization with a specific LCMV mutant elicited nAb responses limited to that clone.
Conclusions:
- LCMV represents a dynamic collection of 'personal' serological submutants that form a 'public' serotype.
- This viral quasispecies strategy challenges classical serotype definitions and may explain immune responses to viruses like HBV, HCV, and HIV.