Patterns of infection with Laguna Negra virus in wild populations of Calomys laucha in the central Paraguayan chaco.
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In 1995, an outbreak of hantavirus pulmonary syndrome occurred in the central Paraguayan chaco. The primary reservoir of the virus, Laguna Negra virus, was identified as the vesper mouse, Calomys laucha. Over a 15-month period, we collected 1,090 small mammals at 12 locations representing 4 habitats common in the central Paraguayan chaco. Calomys laucha was common in agricultural habitats and uncommon in the native forest habitat. Populations of C. laucha were greater during the dry season months and declined during the wet season. A total of 643 small mammals were tested for antibodies cross-reactive to Sin Nombre virus. All of the antibody-positive animals were C. laucha (crude antibody prevalence ratio 12.1% [25 of 206]). Antibody prevalence ratio increased with body size and was more common among male (18%; n = 115) than among female (4%; n = 96) vesper mice. Antibody prevalence ratio was highest among animals from cropland habitats (18%; n = 72), followed by thorn scrub (13%; n = 46) and pastureland (7%; n = 81) and may be positively correlated to the proportion of C. laucha in the small mammal community. These data suggest that community-level dynamics, in addition to population-level dynamics, may be involved in the transmission of the virus through natural populations of vesper mice. (+info)
Hantavirus pulmonary syndrome: the new American hemorrhagic fever.
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The recognition of hantavirus pulmonary syndrome (HPS) after the investigation of a cluster of unexplained respiratory deaths in the southwestern United States during the spring of 1993 showcased our ability to recognize new and emerging diseases, given the correct juxtaposition of a new clinical entity with circumscribed epidemiologic features that are analyzed with novel diagnostic methods. In less than a decade, HPS has become established as a pan-American zoonosis due to numerous viruses maintained by sigmodontine rodents with rodent- and virus-specific epidemiologic profiles. The classical features of the syndrome-acute febrile illness associated with prominent cardiorespiratory compromise after direct contact or inhalation of aerosolized rodent excreta-has been extended to include clinical variants, including disease with frank hemorrhage, that have confirmed that this syndrome is a viral hemorrhagic fever. Efforts are under way to refine prevention strategies, to understand the pathogenesis of the shock, and to identify therapeutic modalities. (+info)
Characterization of HLA-A2.1-restricted epitopes, conserved in both Hantaan and Sin Nombre viruses, in Hantaan virus-infected patients.
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Nine different CTL epitopes, conserved in both Hantaan virus (HTNV) and Sin Nombre virus (SNV), were selected for study. The binding affinity of each peptide with HLA-A2.1 molecules in vitro was determined and antigen-specific responses from seven donors who had a previous field infection with HTNV were examined. Although the strength or frequency of CTL activity showed different patterns in the seven patients, five of seven patients showed significant activity against at least one or more epitope peptides. In particular, the peptide ILQDMRNTI (HTNV, aa 334-342; SNV, aa 333-341), which elicited CTL activity in five patients, was shown to be specifically HLA-A2.1-restricted in partially cloned CD8+ T cells and also induced activated and effector CD8+ T cell-producing T cytotoxic (Tc) type 1 cytokines, such as IL-2 and IFN-gamma. The results suggest that this epitope would serve as a useful component for the intervention of both HTNV and SNV infection. (+info)
Genetic vaccines protect against Sin Nombre hantavirus challenge in the deer mouse (Peromyscus maniculatus).
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We used a deer mouse (Peromyscus maniculatus) infection model to test the protective efficacy of genetic vaccine candidates for Sin Nombre (SN) virus that were known to provoke immunological responses in BALB/c mice (Bharadwaj et al., Vaccine 17, 2836-2843, 1999 ). Protective epitopes were localized in each of four overlapping cDNA fragments that encoded portions of the SN virus G1 glycoprotein antigen; the nucleocapsid gene also was protective. The protective efficacy of glycoprotein gene fragments correlated with splenocyte proliferation in the presence of cognate antigen, but none induced neutralizing antibodies. Genetic vaccines against SN virus can protect outbred deer mice from infection even in the absence of a neutralizing antibody response. (+info)
Shedding and intracage transmission of Sin Nombre hantavirus in the deer mouse (Peromyscus maniculatus) model.
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The mechanism(s) by which Sin Nombre (SN) hantavirus is maintained in deer mouse populations is unclear. Field studies indicate that transmission occurs primarily if not exclusively via a horizontal mechanism. Using an experimental deer mouse infection model in an outdoor laboratory, we tested whether infected rodents shed SN virus in urine, feces, and saliva, whether infected mice transmit infection to naive cage mates, and whether infected dams are able to vertically transmit virus or antibody to offspring. Using pooled samples of urine, feces, and saliva collected from mice infected 8 to 120 days postinoculation (p.i.), we found that a subset of saliva samples, collected between 15 and 90 days p.i., contained viral RNA. Parallel studies conducted on wild-caught, naturally infected deer mice showed a similar pattern of intermittent positivity, also only in saliva samples. Attempts to isolate virus through inoculation of cells or naive deer mice with the secreta or excreta of infected mice were uniformly negative. Of 54 attempts to transmit infection by cohousing infected deer mice with seronegative cage mates, we observed only a single case of transmission, which occurred between 29 and 42 days p.i. Dams passively transferred antibodies to neonatal pups via milk, and those antibodies persisted for at least 2 months after weaning, but none transmitted infection to their pups. Compared to other hantavirus models, SN virus is shed less efficiently and transmits inefficiently among cage mates. Transmission of SN virus among reservoir rodents may require factors that are not required for other hantaviruses. (+info)
Elevated generation of reactive oxygen/nitrogen species in hantavirus cardiopulmonary syndrome.
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Hantavirus cardiopulmonary syndrome (HCPS) is a life-threatening respiratory disease characterized by profound pulmonary edema and myocardial depression. Most cases of HCPS in North America are caused by Sin Nombre virus (SNV), which is carried asymptomatically by deer mice (Peromyscus maniculatus). The underlying pathophysiology of HCPS is poorly understood. We hypothesized that pathogenic SNV infection results in increased generation of reactive oxygen/nitrogen species (RONS), which contribute to the morbidity and mortality of HCPS. Human disease following infection with SNV or Andes virus was associated with increased nitrotyrosine (NT) adduct formation in the lungs, heart, and plasma and increased expression of inducible nitric oxide synthase (iNOS) in the lungs compared to the results obtained for normal human volunteers. In contrast, NT formation was not increased in the lungs or cardiac tissue from SNV-infected deer mice, even at the time of peak viral antigen expression. In a murine (Mus musculus) model of HCPS (infection of NZB/BLNJ mice with lymphocytic choriomeningitis virus clone 13), HCPS-like disease was associated with elevated expression of iNOS in the lungs and NT formation in plasma, cardiac tissue, and the lungs. In this model, intraperitoneal injection of 1400W, a specific iNOS inhibitor, every 12 h during infection significantly improved survival without affecting intrapulmonary fluid accumulation or viral replication, suggesting that cardiac damage may instead be the cause of mortality. These data indicate that elevated production of RONS is a feature of pathogenic New World hantavirus infection and that pharmacologic blockade of iNOS activity may be of therapeutic benefit in HCPS cases, possibly by ameliorating the myocardial suppressant effects of RONS. (+info)
Infection dynamics of Sin Nombre virus after a widespread decline in host populations.
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Many researchers have speculated that infection dynamics of Sin Nombre virus are driven by density patterns of its major host, Peromyscus maniculatus. Few, if any, studies have examined this question systematically at a realistically large spatial scale, however. We collected data from 159 independent field sites within a 1 million-hectare study area in Nevada and California, from 1995-1998. In 1997, there was a widespread and substantial reduction in host density. This reduction in host density did not reduce seroprevalence of antibody to Sin Nombre virus within host populations. During this period, however, there was a significant reduction in the likelihood that antibody-positive mice had detectable virus in their blood, as determined by reverse-transcriptase polymerase chain reaction. Our findings suggest 2 possible causal mechanisms for this reduction: an apparent change in the age structure of host populations and landscape-scale patterns of host density. This study indicates that a relationship does exist between host density and infection dynamics and that this relationship concurrently operates at different spatial scales. It also highlights the limitations of antibody seroprevalence as a metric of infections, especially during transient host-density fluctuations. (+info)
Satellite imagery characterizes local animal reservoir populations of Sin Nombre virus in the southwestern United States.
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The relationship between the risk of hantaviral pulmonary syndrome (HPS), as estimated from satellite imagery, and local rodent populations was examined. HPS risk, predicted before rodent sampling, was highly associated with the abundance of Peromyscus maniculatus, the reservoir of Sin Nombre virus (SNV). P. maniculatus were common in high-risk sites, and populations in high-risk areas were skewed toward adult males, the subclass most frequently infected with SNV. In the year after an El Nino Southern Oscillation (ENSO), captures of P. maniculatus increased only in high-risk areas. During 1998, few sites had infected mice, but by 1999, 1820 of the high-risk sites contained infected mice and the crude prevalence was 30.8%. Only 118 of the low-risk sites contained infected rodents, and the prevalence of infection was lower (8.3%). Satellite imagery identified environmental features associated with SNV transmission within its reservoir population, but at least 2 years of high-risk conditions were needed for SNV to reach high prevalence. Areas with persistently high-risk environmental conditions may serve as refugia for the survival of SNV in local mouse populations. (+info)