Genetic diversity and taxonomical relationships among the tacaribe serocomplex viruses (family arenaviridae)

The three objectives of this dissertation were to 1) examine the natural host relationships and origins of the North American Tacaribe serocomplex viruses (family Arenaviridae), 2) extend our knowledge of the genetic diversity of the Tacaribe serocomplex viruses, and 3) establish genetic criteria for species demarcation within the Arenaviridae. Study 1 -- The results indicated that Neotoma macrotis (large-eared woodrat) is the principal host of Bear Canyon virus, the present-day association of Bear Canyon virus with Peromyscus californicus (California mouse) represents a successful host-jumping event from N. macrotis to P. californicus, and the genomes of the North American arenaviruses are not a product of homologous genetic recombination between ancestors of the present-day South American arenaviruses. Study 2 --The nucleotide sequences of the small genomic segments of 12 strains of Junin virus, 7 strains of Machupo virus, and 11 strains of Guanarito virus were determined to improve our knowledge of strain-to-strain genetic variation within these South American arenavirus species. This new knowledge will enable development of rapid, accurate (sensitive and specific) sequence-based assays for detection of arenavirus-specific RNA in acute-phase clinical specimens from persons affected by South American arenaviral hemorrhagic fevers. Study 3 -- The Eighth Report of the International Committee on Taxonomy of Viruses set forth 4 criteria for demarcation of a species within the Arenaviridae: i) the virus must occupy a unique ecological niche, ii) the virus must represent a unique serotype, iii) whether the virus is pathogenic for humans, and iv) the virus must exhibit significant amino acid sequence differences from strains of other arenaviral species. The purpose was to define “significant amino acid difference” in the context of species demarcation. Pairwise comparisons of the amino acid sequences of the glycoprotein precursors and nucleocapsid proteins of 70 arenaviruses, representing the 22 species in the Arenaviridae, indicated that the minimum nonidentity between strains of different species was 15.8% and 11.2%, respectively. Thus, arenaviruses that exhibit at least 15.8% difference in the glycoprotein precursor and at least 11.2% difference in the nucleocapsid protein may be strains of a novel arenavirus species.