Analysis of Hantavirus Outbreak Genomes Support Spillover Followed by Human-to-Human Transmission
The genome sequences for the RNA virus showed similarity to sequences detected in humans in Andes virus hantavirus outbreaks in 1997 and 2018.
This story has been updated to include comments from virologist Bas Oude Munnink, a lead author of the analysis.
A preliminary analysis of five Hantavirus genomes from the recent cruise ship outbreak suggest that the virus is being passed from person to person, as has been documented in previous outbreaks.
On May 10, Gustavo Palacios, a microbiologist at the Icahn School of Medicine at Mount Sinai posted “Preliminary analysis of Orthohantavirus andesense virus sequences from a cruise-ship related cluster, May 2026,” to Virological.org, a discussion forum for virus evolution and epidemiology. The post represented work by dozens of researchers on four continents to sequence and analyze viral genomes collected from patients associated with the Andes virus (ANDV) outbreak on the MV Hondius cruise ship.
Variants found in the genomes and the similarities between them “support a scenario of initial zoonotic introduction followed by subsequent human‑to‑human transmission during the outbreak,” the researchers wrote.
Moreover, the sequences showed similarity to virus sequences detected in humans in ANDV hantavirus outbreaks in 1997 and 2018. Specifically, “the lack of diversity observed in the outbreak is similar to that observed during a cluster of human-to-human transmission in the Epuyén 2018 outbreak, in Argentina,” they wrote.
The genomes provide crucial details in framing a narrative of how the outbreak unfolded and could be used to validate PCR-based diagnostics, as was the case with COVID-19.
“For this particular outbreak, it might help to improve contact tracing,” said Bas Oude Munnink, a virologist at Erasmus Medical Center in the Netherlands and a leader of the analysis. “In case we start to see additional cases, we can use the genomic information to try to link them to already known patients. But let’s hope it doesn’t spread too much further.”
This analysis follows a May 8 post to Virological.org containing the complete sequence of one of the viral genomes, collected from a Swiss national who had travelled on the cruise ship.
“Preliminary analyses indicate only a relatively small degree of change from the most closely related Argentine sequences,” Damien Tully, a researcher at the London School of Hygiene & Tropical Medicine Uganda Research Unit, told the Science Media Centre about the first genome sequence posted May 8. “At present, there is no clear evidence from this single genome of major genetic shifts, unusual evolution, or reassortment.”
The index case of the virus developed fever, headache, and gastrointestinal symptoms on April 6 and died aboard the ship on April 11. On April 24, around 30 passengers left the ship, traveling to Johannesburg, South Africa and other destinations. The second case died after collapsing in the Johannesburg airport; that case and a third case both tested positive for hantavirus RNA in blood and serum samples in early May.
Clinical samples for the new study were collected, tested, and sequenced at multiple laboratories in South Africa, Senegal, Switzerland, and the Netherlands. On May 5, partial genome sequencing of the L-segment, which codes for a viral polymerase, a strain specific RT-PCR confirmed in two cases the presence of ANDV, a single-stranded RNA virus and the only hantavirus known to pass between humans.
The globehopping travelers infected by the virus presented new challenges. “Typically, when you have an outbreak, every sample and every analysis is being done by one laboratory,” Oude Munnink said. “In this case, it was really a multi-country, multi-laboratory investigation to see if we can shed some light on the hantavirus outbreak at this cruise ship.”
Working together allowed the researchers to distinguish genuine genomic variation from potential analytical artifacts. The various labs applied several different sequencing methods, including sequence-independent single-primer amplification (SISPA), metagenomics, and a capture-based enrichment approach from Twist Bioscience. They then used these library preparations with sequencing from Illumina, Element Biosciences, and Oxford Nanopore Technologies. Initially, there appeared to be more single-letter variants between the genomes, however, comparing them side-by-side resolved most inconsistencies.
The genomic data cannot exclude the possibility that more than one passenger was infected from the same source, the team noted. “Resolving this will require additional epidemiological data, including timelines and contact/exposure histories, together with environmental investigations such as rodent trapping and testing,” they wrote. They also noted that case two, the earliest case that provided a sample, had the lowest coverage and viral load may have been low. Their data and analysis have not yet been peer-reviewed, Oude Munnink added.
One outstanding question is where the spillover event happened. “We’re still trying to figure out where they exactly went and what was the most likely source of exposure to this virus,” Oude Munnink said. ANDV is primarily carried in the long-tailed pygmy mouse (Oligoryzomys longicaudatus); however, the confluence of virus, rodent, and human contact is unknown. A team of researchers based in Argentina are scrambling to answer this question, he noted.
Now that they have the viral genomes sequences, researchers will want to validate that their PCR tests are optimized to detect this strain.
“We are able to detect these sorts of viral threats earlier on, but it is quite worrying that you see all of these different viruses: SARS-CoV-2; we have now Mpox, which is also spreading globally; we have these incidental cases [of ANDV],” Oude Munnink said. “I hope this will keep on being an incident with a limited number of cases, but it does show that we have to truly take care.”