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Andes virus infections in the rodent reservoir and in humans vary across contrasting landscapes in Chile.

ABSTRACT: Hantavirus cardiopulmonary syndrome (HCPS) is an emerging infectious disease first reported in Chile in 1995. Andes hantavirus (ANDV) is responsible for the more than 500 cases of HCPS reported in Chile. Previous work showed that ANDV is genetically differentiated in Chile across contrasting landscapes. To determine whether the reservoir rodent (Oligoryzomys longicaudatus) populations are also geographically segregated, we conducted range-wide spatial genetic analyses of O. longicaudatus in Chile using the mitochondrial DNA cytochrome b gene. Given that landscape structure influences the incidence of hantavirus infections, we also tested 772 O. longicaudatus specimens for antibodies to ANDV captured during the period 2000-2006. Population genetic analyses of O. longicaudatus are largely congruent with those reported for ANDV, with the host primarily differentiated according to three defined ecoregions, Mediterranean, Valdivian rain forest and North Patagonian rain forest. Significant differences in the relative prevalence of anti-ANDV antibodies in rodent samples also were found across the three ecoregions. We relate these results to the number of reported human HCPS cases in Chile, and discuss the importance of landscape differences in light of ANDV transmission to humans and among rodent populations.

SUBMITTER: Torres-Perez F

PROVIDER: S-EPMC2889182 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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Andes virus infections in the rodent reservoir and in humans vary across contrasting landscapes in Chile.

Torres-Pérez Fernando F Palma R Eduardo RE Hjelle Brian B Ferrés Marcela M Cook Joseph A JA

Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 20090724 6

Hantavirus cardiopulmonary syndrome (HCPS) is an emerging infectious disease first reported in Chile in 1995. Andes hantavirus (ANDV) is responsible for the more than 500 cases of HCPS reported in Chile. Previous work showed that ANDV is genetically differentiated in Chile across contrasting landscapes. To determine whether the reservoir rodent (Oligoryzomys longicaudatus) populations are also geographically segregated, we conducted range-wide spatial genetic analyses of O. longicaudatus in Chil ...[more]

PMID: 19632357

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Project description:Andes virus (ANDV) is the predominant etiologic agent of hantavirus cardiopulmonary syndrome (HCPS) in southern South America. In Chile, serologically confirmed human hantavirus infections have occurred throughout a wide latitudinal distribution extending from the regions of Valparaíso (32 to 33 degrees S) to Aysén (46 degrees S) in southern Patagonia. In this study, we found seropositive rodents further north in the Coquimbo region (30 degrees S) in Chile. Rodent seroprevalence was 1.4%, with Oligoryzomys longicaudatus displaying the highest seroprevalence (5.9%), followed by Abrothrix longipilis (1.9%) and other species exhibiting </=0.6% seropositivity. We sequenced partial ANDV small (S) segment RNA from 6 HCPS patients and 32 rodents of four different species collected throughout the known range of hantavirus infection in Chile. Phylogenetic analyses showed two major ANDV South (ANDV Sout) clades, congruent with two major Chilean ecoregions, Mediterranean (Chilean matorral [shrubland]) and Valdivian temperate forest. Human and rodent samples grouped according to geographic location. Phylogenetic comparative analyses of portions of S and medium segments (encoding glycoproteins Gn and Gc) from a subset of rodent specimens exhibited similar topologies, corroborating two major ANDV Sout clades in Chile and suggesting that yet unknown factors influence viral gene flow and persistence throughout the two Chilean ecoregions. Genetic algorithms for recombination detection identified recombination events within the S segment. Molecular demographic analyses showed that the virus is undergoing purifying selection and demonstrated a recent exponential growth in the effective number of ANDV Sout infections in Chile that correlates with the increased number of human cases reported. Although we determined virus sequences from four rodent species, our results confirmed O. longicaudatus as the primary ANDV Sout reservoir in Chile. While evidence of geographic differentiation exists, a single cosmopolitan lineage of ANDV Sout remains the sole etiologic agent for HCPS in Chile.

Project description:Hantavirus cardiopulmonary syndrome (HCPS) is a severe respiratory disease caused by orthohantaviruses in the Americas with a fatality rate as high as 35%. In South America, Andes orthohantavirus (Hantaviridae, Orthohantavirus, ANDV) is a major cause of HCPS, particularly in Chile and Argentina, where thousands of cases have been reported since the virus was discovered. Two strains of ANDV that are classically used for experimental studies of the virus are Chile-9717869, isolated from the natural reservoir, the long-tailed pygmy rice rat, and CHI-7913, an isolate from a lethal human case of HCPS. An important animal model for studying pathogenesis of HCPS is the lethal Syrian golden hamster model of ANDV infection. In this model, ANDV strain Chile-9717869 is uniformly lethal and has been used extensively for pathogenesis, vaccination, and therapeutic studies. Here we show that the CHI-7913 strain, despite having high sequence similarity with Chile-9717869, does not cause lethal disease in Syrian hamsters. CHI-7913, while being able to infect hamsters and replicate to moderate levels, showed a reduced ability to replicate within the tissues compared with Chile-9717869. Hamsters infected with CHI-7913 had reduced expression of cytokines IL-4, IL-6, and IFN-γ compared with Chile-9717869 infected animals, suggesting potentially limited immune-mediated pathology. These results demonstrate that certain ANDV strains may not be lethal in the classical Syrian hamster model of infection, and further exploration into the differences between lethal and non-lethal strains provide important insights into molecular determinants of pathogenic hantavirus infection.Importance:Andes orthohantavirus (ANDV) is a New World hantavirus that is a major cause of hantavirus cardiopulmonary syndrome (HCPS, also referred to as hantavirus pulmonary syndrome) in South America, particularly in Chile and Argentina. ANDV is one of the few hantaviruses for which there is a reliable animal model, the Syrian hamster model, which recapitulates important aspects of human disease. Here we infected hamsters with a human isolate of ANDV, CHI-7913, to assess its pathogenicity compared with the classical lethal Chile-9717869 strain. CHI-7913 had 22 amino acid differences compared with Chile-9717869, did not cause lethal disease in hamsters, and showed reduced ability to replicate in vivo Our data indicate potentially important molecular signatures for pathogenesis of ANDV infection in hamsters and may lead to insights into what drives pathogenesis of certain hantaviruses in humans.

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Andes virus infections in the rodent reservoir and in humans vary across contrasting landscapes in Chile.

Publications

Andes virus infections in the rodent reservoir and in humans vary across contrasting landscapes in Chile.

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