# Genetic sequencing

> Determining the exact nucleotide order of a viral genome. Used to identify variants, retrace transmission chains and compare strains.

Canonical source: https://hantatracker.fr/en/glossary/sequencage-genetique/

**Aliases**: genome sequencing, whole-genome sequencing, WGS, next-generation sequencing, NGS, Sanger sequencing, séquençage génétique

**Genetic sequencing** determines the exact order of nucleotides — A, T (or U for RNA), G and C — that make up a viral genome. For hantaviruses, sequencing makes it possible to **distinguish** one strain from another, **compare** viruses sampled from different patients, and **detect** any mutations associated with a change in viral behaviour. The [MV Hondius](/en/glossary/mv-hondius/) cluster was sequenced for the first time on 5 May 2026 by the Swiss National Reference Centre.

## Technical principle

### From genome to sequence

All RNA viruses, including [Andes virus](/en/glossary/virus-andes/), carry their genetic information in one or more RNA strands. For hantaviruses, the genome is **tri-segmented**:
- **S segment** (~1.8 kb) — encodes the nucleoprotein,
- **M segment** (~3.6 kb) — encodes the envelope glycoproteins Gn and Gc,
- **L segment** (~6.4 kb) — encodes the viral RNA polymerase.

Sequencing produces a chain of letters representing the exact order of each nucleotide. A complete hantavirus sequence contains about 11.8 kilobases (kb).

### Technologies

Three main families coexist:
- **Sanger**: historic technology (1977), accurate but slow. Still used to verify short fragments.
- **Illumina (NGS short-read)**: high throughput, short reads (~150 nt), requires bio-informatics assembly.
- **Oxford Nanopore (NGS long-read)**: long reads (several kb), portable, ideal for field deployment and real-time surveillance.

For hantaviruses, reference labs generally combine Illumina (accuracy) and Nanopore (speed). Turnaround from RNA extraction to a complete sequence is 24-72 hours on modern platforms.

## Application to the MV Hondius cluster

### First sequence — 5 May 2026

The Swiss National Reference Centre for Emerging Viral Infections (**NRZ Emerging Viruses**, Geneva University Hospitals + Institute of Medical Virology, University of Zurich) published the first phylogenetic analysis of Andes virus sequences from the MV Hondius cluster on Virological.org, on 5 May 2026.

Main findings:
- the strain is **genetically very close** to the Epuyén outbreak (Argentina, 2018-2019);
- **no unusual mutation** has been documented, including in the envelope glycoprotein genes (M segment) involved in transmissibility;
- the analysis covers the first samples; exhaustive sequencing of all cases is in progress.

### Variant hypothesis — 12 May 2026

On 12 May 2026 at 17:54, Prof. **Xavier Lescure** (infectious disease specialist, Bichat AP-HP) raised in a press conference the precautionary hypothesis that a possible "variant that may have mutated" could explain the severity of forms observed in the cluster. This hypothesis is not confirmed by the Swiss data of 5 May, which on the contrary show high genetic proximity to known Argentinian strains. Exhaustive sequencing of all cases is expected to settle the question.

## Molecular surveillance

### Phylogeny

Published sequences are deposited in public banks (**GenBank**, NCBI) and analysed with tools such as **Nextstrain**, which build the virus's phylogenetic tree. These trees show which strains are related, when they diverged, and thus retrace transmission chains.

### Variant detection

Nucleotide changes (mutations) are common in RNA viruses, and most are silent or neutral. Particular attention is paid to mutations in:
- the **envelope glycoproteins** (M segment): transmissibility and immune recognition,
- the **polymerase** (L segment): antiviral resistance,
- the **nucleoprotein** (S segment): major antigen, target of serological tests.

## Further considerations

Complete cluster sequencing also makes it possible to **date** approximately the virus's introduction into a population (molecular clock), estimate **diversity** within the cluster, and compare the identified strain to all known global strains via GenBank. For hantaviruses, it is the only way to formally distinguish intra-cluster transmission from multiple introductions from animal reservoirs.