Dr Damien Tully, Associate Professor at the Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine (MRC/UVRI and LSHTM) Uganda Research Unit said:
What can we learn from one sequence and are there still uncertainties?
“From a single complete genome sequence, we can already infer several important things about the outbreak but there are also major limitations to what one sample can tell us. The genome from the Swiss resident linked to the MV Hondius cruise provides the first detailed genetic snapshot of the outbreak strain.
“Across all three hantavirus genome segments, the closest relatives are consistent with one another, which suggests the virus has not undergone reassortment which is a process where segmented viruses exchange genome segments with another strain, potentially creating a novel variant. The absence of evidence for reassortment implies the outbreak virus likely emerged from a single, relatively stable viral lineage rather than from a recent mixing event between different hantaviruses.
“This sequence also offers an early clue about the likely reservoir and geographic origin of the virus by showing which previously known hantavirus strains it most closely resembles. That can help narrow down which host species or ecological source may be involved in the spillover event. However, substantial uncertainties remain as these are based on only one publicly available genome. At this point we still do not know how genetically diverse the outbreak is and whether there are multiple introductions into humans or whether cases came from a single spillover event (a single transmission event from rodents to humans) followed by human-to-human transmission. In addition, a single sequence cannot reliably establish how quickly the virus is evolving during the outbreak.
“Additional sequencing from more patients and potential animal reservoirs will be essential for reconstructing transmission chains and assessing whether the virus is undergoing functionally change. The speed at which this current genome has been publicly shared should be applauded as it provides a valuable early signal but it should be viewed as preliminary evidence rather than a definitive picture of the outbreak’s evolutionary history.
What does this sequence tell us about the virus in this outbreak – are there signs of significant changes or does this look how we would expect it to?
“The sequence is broadly consistent with what we would expect from a hantavirus spillover from its natural reservoir rather than the emergence of a dramatically altered virus. Reassuringly, the closest related sequences are from the 2018–2019 outbreak in Argentina, suggesting the virus remains part of a known viral lineage rather than representing a highly divergent new strain. Viruses naturally accumulate mutations over time as they replicate, so some genetic differences compared with earlier outbreak sequences are expected. Preliminary analyses indicate only a relatively small degree of change from the most closely related Argentine sequences. At present, there is no clear evidence from this single genome of major genetic shifts, unusual evolution, or reassortment.
“These findings are therefore compatible with another spillover event from the natural reservoir host rather than a virus that has substantially changed biologically. However, caution is still needed because conclusions are currently based on only one publicly available genome. Sequencing of additional cases will be important to determine whether the outbreak virus is genetically uniform across patients and whether any meaningful mutations emerge as the outbreak progresses.
What does viral sequencing allow science to do re understanding the current situation?
“Viral sequencing has become an important tool for understanding and monitoring an outbreak in real time. By analysing the virus’s genetic code, we can investigate where the outbreak may have originated, how the virus is evolving, and whether there are any important genetic changes that could affect public health responses.
“Sequencing can help identify the likely source and reservoir of the virus and estimate how long the virus may have been circulating before detection. Comparing genomes from different patients also allows researchers to reconstruct how the outbreak is spreading and determine whether cases are linked through human-to-human transmission or represent separate spillover events from the natural reservoir. It is also valuable for diagnostics. Sequencing enables scientists to check whether mutations have occurred in regions targeted by PCR-based tests, helping confirm that existing diagnostic assays remain accurate and reliable.
“As more sequence data become available from this outbreak, a clearer picture of how this virus is evolving will emerge. For example, if viral genomes from different patients are nearly identical, that would support recent human-to-human transmission. Greater genetic diversity between cases could instead suggest multiple independent spillover events from the reservoir host.”
Prof Piet Maes, President-elect of the Hantavirus Society, and Virologist at the Plotkin Institute, University of Brussels, said:
“I’ve done a quick analysis this afternoon using other available Andes virus sequences from rodents and previously published Andes virus infection clusters. It is of course still too early to draw in-depth conclusions, particularly since this currently remains only a single full-length sequence from the cluster.
“The available phylogenetic and sequence data nevertheless suggest that the Swiss patient isolate represents a relatively typical naturally circulating ANDV lineage originating from the established rodent reservoir in Chile/Argentina, rather than a highly divergent or newly emerged variant. Across all three genomic segments (S, M, and L), the virus clusters consistently with known South American Andes virus strains, including lineages frequently associated with human infections, without evidence of segment incongruence that would suggest recent reassortment. Additional sequence comparisons likewise do not reveal any striking or unusual mutations beyond the degree of variation expected for a wildlife-associated RNA virus lineage evolving in its natural reservoir. The relatively short branch lengths and close phylogenetic relationship to previously described human and rodent isolates further support the interpretation of a recent transmission event from the natural rodent reservoir to a human host — the expected and well-established route of primary Andes virus infection — rather than prolonged cryptic evolution or major adaptive divergence. Importantly, while these genomic findings do not indicate the emergence of a fundamentally novel Andes virus strain, the genomic data alone cannot distinguish between direct zoonotic acquisition and secondary human-to-human transmission in this case, both of which remain biologically plausible for Andes virus.”
Declared interests
Dr Damien Tully: “I have no COIs.”
Prof Piet Maes: “I have no conflicts or interests to declare.”
For all other experts, no reply to our request for DOIs was received. | 
