# A STAT1-Knockout Mouse Model for Chapare Virus Infection and Pathogenesis

## TL;DR

Researchers developed a mouse model to study Chapare virus, a deadly virus in Bolivia, by knocking out a key immune gene.

## Contribution

The study introduces a novel STAT1-knockout mouse model for studying Chapare virus infection and pathogenesis.

## Key findings

- STAT1-/- mice showed partial lethality and a biphasic disease course after CHAPV infection.
- A mouse-adapted CHAPV variant was fully lethal and exhibited similar disease progression.
- The model recapitulates key aspects of human CHAPV disease.

## Abstract

Chapare virus (CHAPV) is an Arenaviridae family member and causative agent of Chapare hemorrhagic fever (CHHF). Endemic to Bolivia, CHAPV was found to be the cause of several outbreaks of CHHF in Bolivia in 2003 and 2019 with high case-fatality rates and instances of human-to-human transmission. The pathogenesis of CHAPV infection is poorly understood, and no vaccines or antivirals are available, in part due to a dearth of available animal models. Mice lacking signal transducer and activator of transcription 1 (STAT1-/-) have been shown to succumb to infection by related arenaviruses, including Machupo virus, and were investigated for their susceptibility to CHAPV infection. Challenge with CHAPV resulted in partial lethality in STAT1-/- mice with a biphasic disease course characterized by initial viral load and pathology in the spleen and liver followed by inflammation and high viral titers in the brain and spinal cord that immediately preceded mortality. Adaptation in the brains of STAT1-/- mice resulted in a fully lethal mouse-adapted CHAPV variant, with a similar biphasic disease course, but virus in tissues was detected more proximal to challenge. The result of this study is a lethal small-animal rodent model for CHAPV that recapitulates many aspects of human CHAPV disease.