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In vivo dynamics of equine infectious anemia viruses emerging during febrile episodes: insertions/duplications at the principal neutralizing domain.

ABSTRACT: Equine infectious anemia virus (EIAV) is a good model for studying mechanisms generating escaped retrovirus variants. We previously sequenced the entire gp90-encoding region of 22 cDNA clones obtained from five antigenically distinct isolates (F1V to F5V) recovered during febrile episodes in horse 493 experimentally infected with the Japanese virulent EIAV strain V70. The results showed that the mutations occurred in the principal neutralizing domain (PND) by insertions/duplications. In this study, we further characterized the PND of virus isolates sequentially recovered during 22 febrile episodes in seven horses newly infected with V70 or one of the V70-derived variants. Sequencing of 70 cDNA clones derived from the 22 episodes confirmed the generation of various new viral quasispecies with insertions/duplications in the PND. Although the insertion/duplication sequences in a total of 92 cDNA clones were extensively heterogeneous, we hypothesized that all the insertions/duplications occurred during reverse transcription from viral genomic RNA to minus strand DNA. The insertion/duplication regions were derived from a part of the PND sequence, which consisted of five small units. These small units, some with various substitutions and/or deletions, were also generated, especially in regions with insertions/duplications. Of particular note was that all these virus variants, except for two cDNA variants, were generated by essentially four different duplication pathways. Thus, these results extend the significance of insertions/duplications in the PND to the novel generation of EIAV in vivo during febrile episodes.

SUBMITTER: Zheng YH

PROVIDER: S-EPMC191736 | biostudies-other | 1997 Jul

REPOSITORIES: biostudies-other

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In vivo dynamics of equine infectious anemia viruses emerging during febrile episodes: insertions/duplications at the principal neutralizing domain.

Zheng Y H YH Sentsui H H Nakaya T T Kono Y Y Ikuta K K

Journal of virology 19970701 7

Equine infectious anemia virus (EIAV) is a good model for studying mechanisms generating escaped retrovirus variants. We previously sequenced the entire gp90-encoding region of 22 cDNA clones obtained from five antigenically distinct isolates (F1V to F5V) recovered during febrile episodes in horse 493 experimentally infected with the Japanese virulent EIAV strain V70. The results showed that the mutations occurred in the principal neutralizing domain (PND) by insertions/duplications. In this stu ...[more]

PMID: 9188568

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Project description:A primary mechanism of lentivirus persistence is the ability of these viruses to evolve in response to biological and immunological selective pressures with a remarkable array of genetic and antigenic variations that constitute a perpetual natural experiment in genetic engineering. A widely accepted paradigm of lentivirus evolution is that the rate of genetic variation is correlated directly with the levels of virus replication: the greater the viral replication, the more opportunities that exist for genetic modifications and selection of viral variants. To test this hypothesis directly, we examined the patterns of equine infectious anemia virus (EIAV) envelope variation during a 2.5-year period in experimentally infected ponies that differed markedly in clinical progression and in steady-state levels of viral replication as indicated by plasma virus genomic RNA assays. The results of these comprehensive studies revealed for the first time similar extents of envelope gp90 variation in persistently infected ponies regardless of the number of disease cycles (one to six) and viremia during chronic disease. The extent of envelope variation was also independent of the apparent steady-state levels of virus replication during long-term asymptomatic infection, varying from undetectable to 10(5) genomic RNA copies per ml of plasma. In addition, the data confirmed the evolution of distinct virus populations (genomic quasispecies) associated with sequential febrile episodes during acute and chronic EIA and demonstrated for the first time ongoing envelope variation during long-term asymptomatic infections. Finally, comparison of the rates of evolution of the previously defined EIAV gp90 variable domains demonstrated distinct differences in the rates of nucleotide and amino acid sequence variation, presumably reflecting differences in the ability of different envelope domains to respond to immune or other biological selection pressures. Thus, these data suggest that EIAV variation can be associated predominantly with ongoing low levels of virus replication and selection in target tissues, even in the absence of substantial levels of plasma viremia, and that envelope variation continues during all stages of persistent infection as the virus successfully avoids clearance by host defense mechanisms.

Dataset Information

In vivo dynamics of equine infectious anemia viruses emerging during febrile episodes: insertions/duplications at the principal neutralizing domain.

Publications

In vivo dynamics of equine infectious anemia viruses emerging during febrile episodes: insertions/duplications at the principal neutralizing domain.

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