Genetic diversity among Bolivian arenaviruses

Abstract

Machupo virus and Chapare virus are members of the Tacaribe serocomplex (virus family Arenaviridae) and etiological agents of hemorrhagic fever in humans in Bolivia. The nucleotide sequences of the complete Z genes, a large fragment of the RNA-dependent RNA polymerase genes, the complete glycoprotein precursor genes, and the complete nucleocapsid protein genes of 8 strains of Machupo virus were determined to increase our knowledge of the genetic diversity among the Bolivian arenaviruses. The results of analyses of the predicted amino acid sequences of the glycoproteins of the Machupo virus strains and Chapare virus strain 200001071 indicated that immune plasma from hemorrhagic fever cases caused by Machupo virus may prove beneficial in the treatment of Bolivian hemorrhagic fever but not hemorrhagic fever caused by Chapare virus.

Fig. 1

Map showing the 9 departments in Bolivia and the locations of (1) Guayaramerín, (2) Magdalena, (3) SanJoaquín, (4) Huacaraje, (5) SanRamón, (6) Chapare, (7) San Ignacio, and (8) Juan Latino. Strains of Machupo virus in this study were from hemorrhagic fever cases sampled from Guayaramerín, Huacaraje, Magdalena, San Joaquín, San Ramón, and Villamontes (location on the map not known) and from vesper mice (Calomys species) captured at sites near San Ramón. The Latino virus prototype strain MARU 10924 was isolated from a large vesper mice (C. callosus) captured near Juan Latino. Other strains of Latino virus were isolated in previous studies from sites near San Ignacio and sites in Brazil near southeastern Bolivia. The Chapare virus strain 200001071 was isolated from a person who lived and worked near the Chapare River in the Department of Cochabamba. The Departments of Beni and Santa Cruz and the northeastern region of the Department of Cochabamba are part of a vast plain that extends from the Andean foothills eastward to the Atlantic coast of central Argentina. The main economic activities in this region include agriculture, logging, and cattle ranching.

Fig. 2

Phylogenetic relationships among 28 strains of Machupo virus based on a neighbor-joining analysis of uncorrected p-model distances generated from an alignment of nucleocapsid protein gene sequences (Table 1), each sequence 634 nt. The lengths of the horizontal branches are proportional to nucleotide sequence divergence, the length of the scale bar is equivalent to a sequence divergence of 0.01, and the numerical values at the nodes indicate the percentage of 1000 bootstrap replicates that supported the interior branches. Bootstrap support values less than 70% are not listed. The Roman numerals indicate the 8 major phylogenetic lineages represented by the 28 strains.

Fig. 3

Phylogenetic relationships among 10 strains of Machupo virus and 15 other New World arenaviruses based on a neighbor-joining analysis of uncorrected genetic (p-model) distances generated from an alignment of full-length nucleocapsid protein gene sequences. The lengths of the horizontal branches are proportional to nucleotide sequence divergence, the length of the scale bar is equivalent to a sequence divergence of 0.05, and the numerical values at the nodes indicate the percentage of 1000 bootstrap replicates that supported the interior branches. Bootstrap support values less than 70% are not listed. The branch labels include (in the following order) virus species, strain, and country of origin. The Lymphocytic choriomeningitis virus (LCMV) strain WE is an Old World arenavirus and was included in the analysis to infer the ancestral node within the group of New World arenaviruses. ALLV, Allpahuayo virus; AMAV, Amapari virus; CHPV, Chapare virus; CPXV, Cupixi virus; FLEV, Flexal virus; GTOV, Guanarito virus; JUNV, Junín virus; LATV, Latino virus; MACV, Machupo virus; OLVV, Oliveros virus; PARV, Paraná virus; PICV, Pichindé virus; PIRV, Pirital virus; SABV, Sabiá virus; TCRV, Tacaribe virus.

Fig. 4

Hydropathy plots of the G1 glycoproteins of (a) Machupo virus strain Carvallo and (b) Chapare virus strain 200001071. The plots were generated using the Hopp–Woods scale and a window size of 7 residues.