# Virological characterization of a new isolated strain of Andes virus involved in the recent person-to-person transmission outbreak reported in Argentina

## TL;DR

A new strain of Andes virus involved in a person-to-person transmission outbreak in Argentina was isolated and characterized, showing high infectivity in hamsters and potential for medical countermeasure development.

## Contribution

The isolation and characterization of a non-adapted wild-type Andes virus strain associated with human-to-human transmission in Argentina.

## Key findings

- The ARG-Epuyén strain was isolated directly from a clinical sample with minimal cell culture adaptation.
- ARG-Epuyén demonstrated high infectiousness and efficient transmission between hamsters.
- ARG-Epuyén was found to be less pathogenic than the previously isolated Andes/ARG strain.

## Abstract

On November 2, 2018, a person-to-person transmission outbreak of Andes virus (Orthohantavirus andesense) began in the small town of Epuyén, Argentina. The strain demonstrated a high capacity for sustained transmission among the human population requiring the implementation of quarantine measures, rigorous contact tracing, isolation of close contacts, and active clinical monitoring to prevent further spread. In this study, we report the isolation of this strain, which we name the ARG-Epuyén strain, directly from a clinical sample after just three passages in cell culture. Complete sequencing revealed only a single amino acid change post-isolation, suggesting that this strain can be considered a non-adapted wild-type Andes virus, marking a critical step toward the development of medical countermeasures against this emerging pathogen. The pathogenicity and transmissibility potential of ARG-Epuyén were evaluated in hamsters, the only animal model for Hantavirus Pulmonary Syndrome. Additionally, this strain was compared with Andes/ARG, an ANDV strain previously isolated from the same geographical area in the Argentinian Patagonia, from a rodent specimen. Our findings revealed high infectiousness and efficient hamster-to-hamster transmission through direct contact experiments, although ARG-Epuyén appeared to be less pathogenic than Andes/ARG.

Hantavirus Pulmonary Syndrome (HPS) in Argentina is a devastating disease with a fatality rates up to 50%. Andes virus (ANDV) is the most frequent causative agent of this infection in Argentina, and was associated with two outbreaks of sustained person-to-person transmission. The paucity of studies for vaccine development and other medical countermeasures (MCMs) against hantaviruses was partially due to the limited access to wild type viral strains and the lack of animal models of diseases. American hantaviruses are very difficult to isolate “in vitro” and “in vivo”, and there are only three strains of ANDV from Chile and Argentina that could be propagated in cell culture, but none of them were associated to person-to-person transmission. Also, the ANDV strain most used in “in vitro” and “in vivo” studies were not involved in human disease and has a unclear history of cell passages. In our work we report the isolation of an ANDV strain associated with disease in humans but, most importantly, with person-to-person transmission (Epuyén outbreak in 2018). In this article we also describe the results of the characterization of this strain proving its ability to infect and spread efficiently between hamsters. Our work represents a critical step towards the development of MCMs against this emerging pathogen.