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Abstract
This report is the first to demonstrate infection of human endothelial cells by Pichinde virus (PIC). PIC infection induces an upregulation of the inducible nitric oxide synthase gene; as well as an increase in detectable nitric oxide (NO). PIC induces an increase in permeability in endothelial cell monolayers which can be abrogated at all measured timepoints with the addition of a nitric oxide synthase inhibitor, indicating a role for NO in the alteration of endothelial barrier function. Because NO has shown antiviral activity against some viruses, viral titer was measured after addition of the NO synthase inhibitor and found to have no effect in altering virus load in infected EC. The NO synthase inhibition also has no effect on levels of activated caspases induced by PIC infection. Taken together, these data indicate NO production induced by Pichinde virus infection has a pathogenic effect on endothelial cell monolayer permeability.
Highlights
Several members of the Arenaviridae family are the agents responsible for hemorrhagic fevers
Effects of Pichinde virus (PIC) infection on HMEC-1 permeability To investigate the effect of viral infection on endothelial cell permeability, HMEC-1s were grown to confluence on porous membrane inserts and subsequently infected with PIC
Because the production of TNF-α is a prominent feature in PIC-infected guinea pigs, the ability of PIC to induce TNFα in HMEC-1 was assayed by ELISA
Summary
Several members of the Arenaviridae family are the agents responsible for hemorrhagic fevers. These members include Junin virus, Machupo virus, and Lassa virus; the etiological agents of Argentine hemorrhagic fever (AHF), Bolivian hemorrhagic fever (BHF), and Lassa fever (LF), respectively [1]. Pichinde virus (PIC) belongs to the New World arenavirus complex along with Junin and Machupo [2]. Unlike Junin and Machupo, PIC is not a human pathogen and does not require high containment facilities to work with this virus. Due to this fact, other groups have used PIC as a model virus for arenavirus infection. Guinea pig infection with PIC has shown pathological similarities with LF, further supporting its use as a model for human Lassa fever [3]
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