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Public versus personal serotypes of a viral quasispecies.

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.

SUBMITTER: Hunziker L

PROVIDER: S-EPMC156318 | biostudies-literature | 2003 May

REPOSITORIES: biostudies-literature

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Public versus personal serotypes of a viral quasispecies.

Hunziker Lukas L Ciurea Adrian A Recher Mike M Hengartner Hans H Zinkernagel Rolf M RM

Proceedings of the National Academy of Sciences of the United States of America 20030502 10

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 ...[more]

PMID: 12730366

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Project description:BackgroundRNA viruses infecting a host usually exist as a set of closely related sequences, referred to as quasispecies. The genomic diversity of viral quasispecies is a subject of great interest, particularly for chronic infections, since it can lead to resistance to existing therapies. High-throughput sequencing is a promising approach to characterizing viral diversity, but unfortunately standard assembly software was originally designed for single genome assembly and cannot be used to simultaneously assemble and estimate the abundance of multiple closely related quasispecies sequences.ResultsIn this paper, we introduce a new Viral Spectrum Assembler (ViSpA) method for quasispecies spectrum reconstruction and compare it with the state-of-the-art ShoRAH tool on both simulated and real 454 pyrosequencing shotgun reads from HCV and HIV quasispecies. Experimental results show that ViSpA outperforms ShoRAH on simulated error-free reads, correctly assembling 10 out of 10 quasispecies and 29 sequences out of 40 quasispecies. While ShoRAH has a significant advantage over ViSpA on reads simulated with sequencing errors due to its advanced error correction algorithm, ViSpA is better at assembling the simulated reads after they have been corrected by ShoRAH. ViSpA also outperforms ShoRAH on real 454 reads. Indeed, 7 most frequent sequences reconstructed by ViSpA from a real HCV dataset are viable (do not contain internal stop codons), and the most frequent sequence was within 1% of the actual open reading frame obtained by cloning and Sanger sequencing. In contrast, only one of the sequences reconstructed by ShoRAH is viable. On a real HIV dataset, ShoRAH correctly inferred only 2 quasispecies sequences with at most 4 mismatches whereas ViSpA correctly reconstructed 5 quasispecies with at most 2 mismatches, and 2 out of 5 sequences were inferred without any mismatches. ViSpA source code is available at http://alla.cs.gsu.edu/~software/VISPA/vispa.html.ConclusionsViSpA enables accurate viral quasispecies spectrum reconstruction from 454 pyrosequencing reads. We are currently exploring extensions applicable to the analysis of high-throughput sequencing data from bacterial metagenomic samples and ecological samples of eukaryote populations.

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Public versus personal serotypes of a viral quasispecies.

Publications

Public versus personal serotypes of a viral quasispecies.

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