Abstract
Andes virus (ANDV) is the most common causative agent of hantavirus pulmonary syndrome (HPS) in the Americas, and is the only hantavirus associated with human-to-human transmission. Case fatality rates of ANDV-induced HPS are approximately 40%. There are currently no effective vaccines or antivirals against ANDV. Since HPS severity correlates with viral load, we tested small interfering RNA (siRNA) directed against ANDV genes as a potential antiviral strategy. We designed pools of 4 siRNAs targeting each of the ANDV genome segments (S, M, and L), and tested their efficacy in reducing viral replication in vitro. The siRNA pool targeting the S segment reduced viral transcription and replication in Vero-E6 cells more efficiently than those targeting the M and L segments. In contrast, siRNAs targeting the S, M, or L segment were similar in their ability to reduce viral replication in human lung microvascular endothelial cells. Importantly, these siRNAs inhibit ANDV replication even if given after infection. Taken together, our findings indicate that siRNAs targeting the ANDV genome efficiently inhibit ANDV replication, and show promise as a strategy for developing therapeutics against ANDV infection.
Highlights
Andes virus (ANDV), a New World pathogenic hantavirus, causes hantavirus pulmonary syndrome (HPS) in humans, with case fatality rates of 40% [1,2]
Results small interfering RNA (siRNA) inhibits ANDV protein synthesis To determine if siRNA against the ANDV genome inhibits
ANDV infection in vitro, we generated siRNA pools targeting each of the 3 ANDV genomic segments (Table S1)
Summary
Andes virus (ANDV), a New World pathogenic hantavirus, causes hantavirus pulmonary syndrome (HPS) in humans, with case fatality rates of 40% [1,2]. ANDV is the major cause of HPS in South America, and has been associated with the most HPS cases to date. It has been classified as a category A pathogen, and is the only hantavirus known to be capable of human-to-human transmission [3,4]. ANDV, a member of the Bunyaviridae family, is an enveloped virus with a tri-segmented, negative-sense, single-stranded RNA genome of approximately 11 kb [5]. N interacts with host mRNA and viral RNA during viral replication. The L protein is responsible for replicating and transcribing the viral genome
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