Earlier this month, a cluster of severe acute respiratory illnesses aboard the Dutch-flagged cruise ship MV Hondius was reported to the World Health Organization (WHO). The infections have since been confirmed as part of a hantavirus outbreak, with a total of 11 cases, including three deaths, now confirmed. Although the risk to the global population is low, according to the WHO, the news has understandably stoked concern, and with it a lot of questions, about this little-known group of viruses.
In light of the recent outbreak, here’s everything you need to know about hantaviruses, including how they spread, signs to look out for and where we’re at with treatments.
What is hantavirus?
Hantaviruses are zoonotic viruses that naturally infect rodents. As we’ve seen in recent weeks, they are occasionally transmitted to humans, where they can cause severe respiratory illness and, sometimes, death.
Many hantavirus species have been identified worldwide, but only a handful are known to cause human disease. Those that do are associated with two conditions: hantavirus pulmonary syndrome (HPS), which predominantly affects the lungs and heart, and hemorrhagic fever with renal syndrome (HFRS), impacting the kidneys and blood vessels. These distinct diseases are caused by different strains of hantavirus and are found in different parts of the world.
Infection typically occurs through contact with infected rodents and is not usually spread from person-to-person; however, limited human-to-human transmission has been documented for one hantavirus, the Andes virus (Orthohantavirus andesense), which is endemic in some parts of the Americas. This strain of hantavirus causes HPS and was identified in the recent cruise ship outbreak.
Hantavirus epidemiology
It is estimated that there are between 10,000 and over 100,000 hantavirus cases each year, the bulk of which are reported in Asia and Europe, per the WHO. The diseases vary by type of virus and geographical location, with HPS mainly reported in North, Central and South America, while HFRS is most prominent in Europe and Asia. Case fatality rates differ geographically and by strain too, tending to be between
The first description of a hantavirus disease dates back to the 1950s, when an HFRS outbreak, then known as Korean Hemerologic fever, was reported among US soldiers fighting in the Korean War. HPS wasn’t recognized until much later, when a spate of cases popped up in Arizona, Colorado, New Mexico and Utah in 1993.
A 1996 outbreak in Argentina, involving 20 people in three different cities, marked the first time that Andes virus was shown to be transmitted from person to person.
What are the symptoms of hantavirus?
In humans, symptoms generally start 1 to 8 weeks after exposure, depending on the type of virus, and include: fever, headache, muscle aches, abdominal pain, nausea and vomiting.
In HPS, patients may go on to develop a cough, shortness of breath, accumulation of fluid in the lungs and shock. Meanwhile, later stages of HFRS are characterized by low blood pressure, bleeding disorders and kidney failure.
History of hantavirus discovery
Hantaviruses belong to the family Hantaviridae, within the order Bunyavirales. The first hantavirus, the causative agent behind Korean Hemerologic fever, was isolated in 1978 from infected field mice (Apodemus agrarius) near Hantan river in South Korea. It was named Hantaan virus (Orthohantavirus hantanense) after its location.
In 1981, a strain of this virus (76-118) was grown in an A549 cell line, and electron microscopy revealed that it was a new member of the Bunyaviridae family, which includes arthropod- or rodent-borne, spherical, enveloped RNA viruses. Also in 1981, the genus Hantavirus was introduced, named after the founding member, Hantaan virus. It was renamed Orthohantavirus in 2018. The global distribution of hantaviruses was only recognized in 1993 after the HPS outbreak in the Southwestern United States.
Since then, electron microscopy and biochemical characterization have revealed that hantaviruses have enveloped virions with a diameter of 80 to 210 nm, decorated with spikes derived from a pair of glycoproteins (Gn and Gc), and contain three separate nucleocapsid structures encapsulating distinct negative-sense RNAs, which encode an RNA-dependent RNA polymerase, surface glycoproteins and a nucleocapsid protein, respectively.
How are hantaviruses transmitted?
Human hantavirus infection is primarily acquired through contact with infected rodents, including via urine, feces or saliva on contaminated surfaces. Transmission can also occur, though less frequently, through bites.
Activities that increase contact with rodents, like cleaning or sleeping in buildings with rodent infestations, farming and forestry work can up the risk.
How do flu viruses infect cells? New microscopy method captures complex ‘dance’
How flu viruses enter cells has been directly observed thanks to a new microscopy technique with the potential to revolutionize research on virus–host interactions and drug discovery.
Hantavirus pathogenesis
Once inside the body, hantaviruses enter host cells using β3 integrins that are expressed on platelets and endothelial cells. Beyond this, the mechanisms of disease are not well understood. Both HFRS and HPS appear to be linked to immune and inflammatory mediators that result in an increase in vascular permeability. In HPS, this results in pulmonary edema, and in HFRS, this vascular leak is into the retroperitoneum.
The host immune response appears to play a major role in disease severity. In fatal HPS, large numbers of cells producing interleukin-1 (IL-1), IL-6, tumor necrosis factor, IL-2, IL-4 and interferon-gamma are present in the lungs and spleen, indicating that local cytokine production, by CD8+ and CD4+ cytotoxic T-cells, could be important in the pathogenesis of HPS.
How is hantavirus detected?
A number of methods can be used to diagnose HPS and HFRS, including serologic testing, such as enzyme-linked immunosorbent assays (ELISA) to detect IgM antibodies, as well as RT-PCR to detect viral RNA in bodily fluids and immunohistochemistry to identify viral antigens in tissue samples.
Whole genome sequencing also plays an important role in infectious disease diagnosis; however, obtaining complete genomic sequences from emerging viruses is difficult. One 2024 study from Korea University College of Medicine (Seoul, Korea) sought to navigate this this particular minefield, showcasing nanopore-based Flongle sequencing as an effective, cost-efficient and rapid method for detecting hantavirus genomes in rodents. The approach enables virtually whole-genome sequencing within 3 hours and could transform hantavirus detection and outbreak management.
Are there any hantavirus treatments?
Unfortunately, there are currently no specific treatments or vaccines for hantavirus diseases. Care focuses on management of symptoms, while prevention relies on reducing contact between people and infected rodents.
That said, there are a number of recent studies offering promise of hantavirus therapies. Earlier this year, researchers from The University of Texas at Austin (TX, USA) took a crucial first step towards long-overdue vaccines and antibody therapies for Andes hantavirus, establishing a cryo-electron microscopy workflow to create the highest resolution 3D map to date of the Andes virus glycoprotein tetramer – a protein complex the virus uses to infect host cells. This revealed previously uncharacterized features of glycoprotein organization, stability and pH sensing, which enabled the team to design a vaccine candidate made up of self-amplifying replicon RNA encoding Andes virus-like particles. This was used to immunize mice and was found to induce neutralizing antibodies against the Andes virus, laying a foundation for structure-based hantavirus vaccine design.
Another team, based at Air Force Medical University (Xi’an, China), is investigating nucleic acid vaccines against Hantaan virus. They created DNA and mRNA versions of a vaccine containing prefusion-stabilized Hantaan virus glycoprotein, and used them to immunize female BALB/c mice. Both elicited robust neutralizing antibodies, which protected mice against high-dose Hantaan virus, thus representing an encouraging approach for advanced Orthohantavirus vaccine development.
Although still in their very early days, preclinical breakthroughs like these provide some hope for hantavirus treatment and prevention at some point in the future.