Clusters of Hantavirus Infection, Southern Argentina

Hantavirus pulmonary syndrome (HPS) is a highly pathogenic disease (40% case fatality rate) carried by rodents chronically infected with certain viruses within the genus Hantavirus of the family Bunyaviridae. The primary mode of transmission to humans is thought to be inhalation of excreta from infected rodents; however, ingestion of contaminated material and rodent bites are also possible modes of transmission. Person-to-person transmission of HPS caused by one species of hantavirus, Andes virus (ANDV), has been reported. Previously, we reported that ANDV injected intramuscularly causes a disease in Syrian hamsters that closely resembles HPS in humans. Here we tested whether ANDV was lethal in hamsters when it was administered by routes that more accurately model the most common routes of human infection, i.e., the subcutaneous, intranasal, and intragastric routes. We discovered that ANDV was lethal by all three routes. Remarkably, even at very low doses, ANDV was highly pathogenic when it was introduced by the mucosal routes (50% lethal dose [LD 50 ], ϳ100 PFU). We performed passive transfer experiments to test the capacity of neutralizing antibodies to protect against lethal intranasal challenge. The neutralizing antibodies used in these experiments were produced in rabbits vaccinated by electroporation with a previously described ANDV M gene-based DNA vaccine, pWRG/AND-M. Hamsters that were administered immune serum on days ؊1 and ؉5 relative to challenge were protected against intranasal challenge (21 LD 50 ). These findings demonstrate the utility of using the ANDV hamster model to study transmission across mucosal barriers and provide evidence that neutralizing antibodies produced by DNA vaccine technology can be used to protect against challenge by the respiratory route.Hantaviruses are rodent-borne enveloped viruses that have a trisegmented, negative-sense, single-stranded RNA genome and are members of the family Bunyaviridae (20,24, 28). Pathogenic hantaviruses found in Europe and Asia cause a vascular leak disease known as hemorrhagic fever with renal syndrome. In 1993, pathogenic hantaviruses were discovered in the Americas (reviewed in references 14 and 21). The "New World" hantaviruses cause a vascular leak syndrome characterized by massive pulmonary edema followed by shock. Hantavirus pulmonary syndrome (HPS), also known as hantavirus cardiopulmonary syndrome, is highly lethal (30 to 50% case fatality rate), and at least one of the HPS-associated hantaviruses, Andes virus (ANDV), can spread from person to person (7,19,25,27).ANDV is the only pathogenic hantavirus for which there is an animal model that closely resembles human disease. When ANDV is injected into Syrian hamsters, the animals develop a disease that closely mimics human HPS (12). Similarities include the incubation time, rapid disease onset, infected endothelial cells, pulmonary edema, pleural effusion, thrombocytopenia, neutrophilia, and shock (4,12). This model has been used to test candidate medical countermeasures to prevent and t...

Section: Discussionmentioning

confidence: 57%

Immune Serum Produced by DNA Vaccination Protects Hamsters against Lethal Respiratory Challenge with Andes Virus

Hooper

Ferro

Wahl‐Jensen

2008

“…Demonstration of a widespread and well-established hantavirus enzootic in Chile indicates that ANDV Sout is likely to remain a public health concern with significant outbreak risk. The phylogenetic split observed in our study demonstrates that unknown factors contribute to the widespread characteristics (18,34,38), it is imperative that we understand the underlying historical and ecological factors of ANDV in the hope of designing and implementing effective preventive and surveillance strategies.…”

Section: Discussionmentioning

confidence: 99%

Ecology, Genetic Diversity, and Phylogeographic Structure of Andes Virus in Humans and Rodents in Chile

Medina

Torres-Pérez

Galeno

et al. 2009

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°S) to Aysén (46°S) in southern Patagonia. In this study, we found seropositive rodents further north in the Coquimbo region (30°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 (

“…Hantavirus pulmonary syndrome (HPS), caused by New World hantaviruses (e.g., Sin Nombre virus [SNV] and Andes virus [ANDV]) found across the Americas, primarily affects the lungs and heart and has an overall mortality rate of ϳ40%, despite state-of-the-art treatment in modern intensive care facilities. Moreover, there is evidence that ANDV can be transmitted person to person (44,77,82). There are no FDAlicensed vaccines or therapies for these neglected diseases.…”

mentioning

confidence: 99%

T Cells Are Not Required for Pathogenesis in the Syrian Hamster Model of Hantavirus Pulmonary Syndrome

Hammerbeck

Hooper

2011

Andes virus (ANDV) is associated with a lethal vascular leak syndrome in humans termed hantavirus pulmonary syndrome (HPS). In hamsters, ANDV causes a respiratory distress syndrome closely resembling human HPS. The mechanism for the massive vascular leakage associated with HPS is poorly understood; however, T cell immunopathology has been implicated on the basis of circumstantial and corollary evidence. Here, we show that following ANDV challenge, hamster T cell activation corresponds with the onset of disease. However, treatment with cyclophosphamide or specific T cell depletion does not impact the course of disease or alter the number of surviving animals, despite significant reductions in T cell number. These data demonstrate, for the first time, that T cells are not required for hantavirus pathogenesis in the hamster model of human HPS. Depletion of T cells from Syrian hamsters did not significantly influence early events in disease progression. Moreover, these data argue for a mechanism of hantavirus-induced vascular permeability that does not involve T cell immunopathology.