Cell Models for Andes Virus and Hantavirus Cardiopulmonary Syndrome Research

Recent Andes Virus Cluster

WHO published its third Disease Outbreak News report on the hantavirus cluster linked to the MV Hondius cruise ship on 13 May 2026. The number of reported cases continued to increase after the previous Disease Outbreak News report on 8 May. As of 13 May, WHO reported 11 cases, including three deaths: eight laboratory-confirmed Andes virus (ANDV) infections, two probable cases, and one inconclusive case undergoing further testing. Clinical presentations included respiratory and gastrointestinal symptoms, and laboratory-confirmed cases were identified as Andes virus infections. Together, the clinical features and laboratory findings are consistent with hantavirus pulmonary syndrome (HPS), also known as hantavirus cardiopulmonary syndrome (HCPS).

What is Hantavirus and Hantavirus Pulmonary Syndrome (HPS)?

Hantaviruses are rodent-borne viruses that can cause severe human disease. New World hantaviruses in the Americas, such as Sin Nombre virus and Andes virus, are mainly associated with HPS/HCPS, which affects the respiratory and cardiovascular systems and can lead to pulmonary edema, respiratory failure, hypotension, and shock. Old World hantaviruses in Europe and Asia, such as Hantaan, Dobrava, Puumala, and Seoul virus, are mainly associated with hemorrhagic fever with renal syndrome (HFRS), which primarily affects the kidneys and blood vessels and may present with fever, abdominal or back pain, thrombocytopenia, proteinuria or hematuria, and kidney injury. Human hantavirus infection is usually acquired through exposure to the urine, feces, or saliva of infected rodents. Among hantaviruses, Andes virus is notable because limited human-to-human transmission has been documented, typically among close contacts with prolonged exposure.

HPS/HCPS is largely a pulmonary vascular leakage disease. Pathogenic hantaviruses can infect endothelial cells nonlytically and alter endothelial barrier function without causing extensive endothelial cell destruction. In Andes virus infection, studies have reported increased VEGF secretion and reduced VE-cadherin in human primary lung endothelial cells, mechanisms that may contribute to increased endothelial permeability and pulmonary edema. Human Pulmonary Microvascular Endothelial Cells (ARP0132) are therefore a highly relevant cell model for studies of lung capillary leakage, endothelial permeability, barrier disruption, VEGF/VE-cadherin signaling, and cytokine responses in hantavirus-associated cardiopulmonary disease.

Pulmonary and Immune Cell Models for Host Response Studies

Although endothelial cells are central to HCPS pathogenesis, the disease clinically affects the lung and is characterized by pulmonary edema and respiratory failure. Some studies have also investigated alveolar or airway epithelial injury, epithelial-endothelial crosstalk, and lung-barrier damage. Meza-Fuentes et al. (2023) examined soluble RAGE as a potential biomarker of pulmonary epithelial damage in HCPS and suggested that epithelial injury may also contribute to disease severity. Human Pulmonary Alveolar Epithelial Cells (ARP0136), Human Bronchial Epithelial Cells (ARP0138), and Human Small Airway Epithelial Cells (ARP0141) may therefore support studies of alveolar injury, epithelial barrier response, surfactant-related biology, edema-associated lung damage, airway responses, and respiratory epithelial inflammation.

HCPS severity is not determined only by viral infection of target cells. Immune activation, cytokine responses, T cells, monocytes/macrophages, dendritic cells, and NK-cell responses are also important research areas. Hepojoki et al. (2014) reviewed hantavirus interactions with both hematopoietic and endothelial cells and discussed their relationship to increased vascular permeability. Immune cell models such as PBMCs, monocytes, macrophages, dendritic cells, T cells, and NK cells may therefore be useful for studying host inflammatory responses, antiviral immunity, and immunopathogenesis in hantavirus infection.

A549 and Engineered Models for Mechanistic Research

A549 cells may also be useful as a supporting model for hantavirus research. A549 is a human alveolar epithelial-like lung carcinoma cell line and is widely used as a robust pulmonary epithelial model with functional antiviral-response pathways. Some hantavirus studies have used A549 cells to investigate type I/III interferon responses, ISG induction, TLR/RIG-I-like signaling, apoptosis-related pathways, and viral immune antagonism. However, because Andes virus-associated HCPS is strongly linked to endothelial infection and vascular leakage, A549 should be positioned as a complementary lung epithelial and innate immune-response model rather than the primary disease-relevant model.

Engineered cell models may provide additional tools to study hantavirus entry mechanisms, especially for Andes virus. Protocadherin-1 (PCDH1) has been identified as an important entry factor for New World hantaviruses that cause HPS/HCPS, including Andes virus and Sin Nombre virus. Studies have shown that specific mutations in the PCDH1 extracellular domain can disrupt hantavirus glycoprotein recognition and substantially protect Syrian hamsters from ANDV-induced pulmonary disease and death. Ascent Research provides PCDH1 Knockout A549 Cells (ARG10353), which may support receptor-pathway, viral entry, pseudovirus, or host-factor studies related to Andes virus and hantavirus cardiopulmonary syndrome, depending on the customer’s assay design and biosafety setting.

Biosafety Notice and Research Use Only

These products are intended for research use only; studies involving infectious Andes virus or clinical specimens should be conducted under appropriate institutional biosafety approval and containment conditions.

Reference

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