“Super-Spreaders” and Person-to-Person Transmission of Andes Virus in Argentina

ABSTRACT 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 [LD50], ∼100 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 LD50). 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.

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Novel infection of pericytes by Andes virus enhances endothelial cell permeability

Virus Research ◽

10.1016/j.virusres.2021.198584 ◽

2021 ◽

Vol 306 ◽

pp. 198584

Author(s):

Ramon D. Perez ◽

Elena E. Gorbonova ◽

Erich R. Mackow

Keyword(s):

Endothelial Cell ◽

Cell Permeability ◽

Andes Virus ◽

Endothelial Cell Permeability

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Person-to-Person Transmission of Andes Virus

Emerging Infectious Diseases ◽

10.3201/eid1112.050501 ◽

2005 ◽

Vol 11 (12) ◽

pp. 1848-1853 ◽

Cited By ~ 146

Author(s):

Valeria P. Martinez ◽

Carla Bellomo ◽

Jorge San Juan ◽

Diego Pinna ◽

Raul Forlenza ◽

...

Keyword(s):

Andes Virus

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Case report: T-cell responses during clearance of andes virus from blood cells 2 months after severe hantavirus cardiopulmonary syndrome

Journal of Medical Virology ◽

10.1002/jmv.21302 ◽

2008 ◽

Vol 80 (11) ◽

pp. 1947-1951 ◽

Cited By ~ 7

Author(s):

Tobias Manigold ◽

Jessica Martinez ◽

Ximena Lazcano ◽

Chunyan Ye ◽

Shaina Schwartz ◽

...

Keyword(s):

Case Report ◽

T Cell ◽

Blood Cells ◽

T Cell Responses ◽

Cell Responses ◽

Andes Virus

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Andes Virus Disrupts the Endothelial Cell Barrier by Induction of Vascular Endothelial Growth Factor and Downregulation of VE-Cadherin

Journal of Virology ◽

10.1128/jvi.01405-10 ◽

2010 ◽

Vol 84 (21) ◽

pp. 11227-11234 ◽

Cited By ~ 74

Author(s):

Punya Shrivastava-Ranjan ◽

Pierre E. Rollin ◽

Christina F. Spiropoulou

Keyword(s):

Vascular Endothelial Growth Factor ◽

Endothelial Cells ◽

Endothelial Cell ◽

Growth Factor ◽

Virus Replication ◽

Cell Permeability ◽

Hantavirus Infection ◽

Vascular Endothelial ◽

Andes Virus ◽

Endothelial Growth Factor

ABSTRACT Hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS) are severe diseases associated with hantavirus infection. High levels of virus replication occur in microvascular endothelial cells but without a virus-induced cytopathic effect. However, virus infection results in microvascular leakage, which is the hallmark of these diseases. VE-cadherin is a major component of adherens junctions, and its interaction with the vascular endothelial growth factor (VEGF) receptor, VEGF-R2, is important for maintaining the integrity of the endothelial barrier. Here we report that increased secreted VEGF and concomitant decreased VE-cadherin are seen at early times postinfection of human primary lung endothelial cells with an HPS-associated hantavirus, Andes virus. Furthermore, active virus replication results in increased permeability and loss of the integrity of the endothelial cell barrier. VEGF binding to VEGF-R2 is known to result in dissociation of VEGF-R2 from VE-cadherin and in VE-cadherin activation, internalization, and degradation. Consistent with this, we showed that an antibody which blocks VEGF-R2 activation resulted in inhibition of the Andes virus-induced VE-cadherin reduction. These data implicate virus induction of VEGF and reduction in VE-cadherin in the endothelial cell permeability seen in HPS and suggest potential immunotherapeutic targets for the treatment of the disease.

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Vesicular Stomatitis Virus-Based Vaccine Protects Hamsters against Lethal Challenge with Andes Virus

Journal of Virology ◽

10.1128/jvi.00794-11 ◽

2011 ◽

Vol 85 (23) ◽

pp. 12781-12791 ◽

Cited By ~ 45

Author(s):

K. S. Brown ◽

D. Safronetz ◽

A. Marzi ◽

H. Ebihara ◽

H. Feldmann

Keyword(s):

Vesicular Stomatitis Virus ◽

Lethal Challenge ◽

Andes Virus ◽

Vesicular Stomatitis

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Analysis of Hantavirus Genetic Diversity in Argentina: S Segment-Derived Phylogeny

Journal of Virology ◽

10.1128/jvi.76.8.3765-3773.2002 ◽

2002 ◽

Vol 76 (8) ◽

pp. 3765-3773 ◽

Cited By ~ 38

Author(s):

Marlene C. Bohlman ◽

Sergey P. Morzunov ◽

John Meissner ◽

Mary Beth Taylor ◽

Kimiko Ishibashi ◽

...

Keyword(s):

Genetic Diversity ◽

Dominant Factor ◽

South American ◽

Protein Amino Acid ◽

The Andes ◽

Andes Virus ◽

Virus Genotypes ◽

The Common ◽

High Level ◽

Virus Strains

ABSTRACT Nucleotide sequences were determined for the complete S genome segments of the six distinct hantavirus genotypes from Argentina and for two cell culture-isolated Andes virus strains from Chile. Phylogenetic analysis indicates that, although divergent from each other, all Argentinian hantavirus genotypes group together and form a novel phylogenetic clade with the Andes virus. The previously characterized South American hantaviruses Laguna Negra virus and Rio Mamore virus make up another clade that originates from the same ancestral node as the Argentinian/Chilean viruses. Within the clade of Argentinian/Chilean viruses, three subclades can be defined, although the branching order is somewhat obscure. These are made of (i) “Lechiguanas-like” virus genotypes, (ii) Maciel virus and Pergamino virus genotypes, and (iii) strains of the Andes virus. Two hantavirus genotypes from Brazil, Araraquara and Castello dos Sonhos, were found to group with Maciel virus and Andes virus, respectively. The nucleocapsid protein amino acid sequence variability among the members of the Argentinian/Chilean clade does not exceed 5.8%. It is especially low (3.5%) among oryzomyine species-associated virus genotypes, suggesting recent divergence from the common ancestor. Interestingly, the Maciel and Pergamino viruses fit well with the rest of the clade although their hosts are akodontine rodents. Taken together, these data suggest that under conditions in which potential hosts display a high level of genetic diversity and are sympatric, host switching may play a prominent role in establishing hantavirus genetic diversity. However, cospeciation still remains the dominant factor in the evolution of hantaviruses.

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A High-Throughput Flow Cytometry Screen Identifies Molecules That Inhibit Hantavirus Cell Entry

SLAS DISCOVERY Advancing Life Sciences ◽

10.1177/2472555218766623 ◽

2018 ◽

Vol 23 (7) ◽

pp. 634-645 ◽

Cited By ~ 1

Author(s):

Tione Buranda ◽

Catherine Gineste ◽

Yang Wu ◽

Virginie Bondu ◽

Dominique Perez ◽

...

Keyword(s):

Flow Cytometry ◽

High Throughput ◽

Case Fatality ◽

Hemorrhagic Fever ◽

Severe Form ◽

Chemical Library ◽

Binding Interaction ◽

Andes Virus ◽

Bona Fide ◽

Infection Inhibition

Hantaviruses cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS), which infects more than 200,000 people worldwide. Sin Nombre virus (SNV) and Andes virus (ANDV) cause the most severe form of HCPS, with case fatality ratios of 30%–40%. There are no specific therapies or vaccines for SNV. Using high-throughput flow cytometry, we screened the Prestwick Chemical Library for small-molecule inhibitors of the binding interaction between UV-inactivated and fluorescently labeled SNVR18 particles, and decay-accelerating factor (DAF) expressed on Tanoue B cells. Eight confirmed hit compounds from the primary screen were investigated further in secondary screens that included infection inhibition, cytotoxicity, and probe interference. Antimycin emerged as a bona fide hit compound that inhibited cellular infection of the major HCPS (SNV)- and HCPS (Hantaan)-causing viruses. Confirming our assay’s ability to detect active compounds, orthogonal testing of the hit compound showed that antimycin binds directly to the virus particle and blocks recapitulation of physiologic integrin activation caused by SNV binding to the integrin PSI domain.

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