Hantavirus: how does the virus hijack the cell?

By Ana Espino | Published on May 11, 2026 | 4 min read



Hantaviruses are zoonotic viruses belonging to the order Bunyavirales. They primarily infect animal reservoirs, especially rodents and certain insectivores, and can then be transmitted to humans through inhalation of contaminated particles. In humans, they can cause severe diseases such as hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS). These infections may be severe or even fatal depending on the viral species involved.

To date, there is no approved vaccine or truly effective specific antiviral treatment for hantavirus infections in humans. This limitation is partly due to the fact that several stages of the viral cycle remain poorly understood, including viral entry, replication, and particle assembly. Hantaviruses grow slowly in cell culture and often produce low quantities of virus. In addition, available in vitro models do not always accurately reproduce natural infection.

In this context, the objective of this review was to summarize the hantavirus replication cycle using recent structural virology data. Understanding these mechanisms is essential for identifying new therapeutic targets. The authors focused on the contribution of advanced techniques to better understand virion organization, viral entry, membrane fusion, genome replication, and viral particle assembly.

How does the virus take control ?

Recent structural virology data were analyzed, including viral entry into the cell, membrane fusion, genome replication and transcription, viral RNA encapsidation, assembly of new virions, and viral release from the cell. The authors notably relied on findings obtained through cryo-electron tomography, cryo-electron microscopy, and crystallography.

A detailed analysis of the hantavirus replication cycle was generated. These viruses possess an envelope covered with two main proteins, Gn and Gc, which allow them to enter cells. Inside, they contain three RNA segments associated with viral proteins, particularly the N protein, which protects the genome, and the L protein, which enables genome replication.

To infect a cell, the virus first attaches to receptors located on the cell surface. Several possible receptors have been identified, including integrins, although the exact mechanism is still not fully understood. After attachment, the virus enters the cell through endocytosis.

Once inside, the acidic environment of the endosome triggers a conformational change in viral proteins, especially the Gc protein. This change allows fusion between the viral envelope and the cellular membrane, leading to release of the viral genome into the cytoplasm.

The virus can then begin to replicate. The L protein synthesizes new viral RNAs and messenger RNAs, while the N protein protects and organizes the viral genome. Hantaviruses also use a mechanism known as “cap-snatching,” in which they hijack fragments of host messenger RNAs to produce their own viral RNAs.

Finally, new viral particles are assembled. Gn and Gc proteins are synthesized and transported to the Golgi apparatus, where they participate in the formation of new virions. The release of viral particles remains under debate: some hantaviruses may exit through the Golgi pathway, while others may bud directly from the cell surface.

A viral cycle still full of mysteries

Hantaviruses are zoonotic viruses capable of causing severe renal or pulmonary syndromes in humans. Major challenges concern the precise understanding of the viral cycle, including the receptors used, entry pathways, replication sites, assembly mechanisms, and viral release processes. These unresolved questions still limit the development of targeted treatments and vaccines.

In this context, the study aimed to synthesize recent knowledge about the hantavirus replication cycle, with a particular emphasis on the contributions of structural virology. The article shows that structural approaches have greatly improved understanding of hantaviruses, especially regarding virion organization, membrane fusion, and genome encapsidation. These findings make it possible to identify key stages of the viral cycle that could become therapeutic targets. However, many questions remain open, particularly concerning interactions between the virus and the host cell.

Future research may help develop better infection models, precisely identify the cellular receptors used by hantaviruses, and better characterize the stages of virion assembly and release. Ultimately, this knowledge could support the development of new antivirals targeting viral entry, membrane fusion, the L polymerase, or viral particle assembly.




About the author – Ana Espino
PhD in Immunology, specialized in Virology  
As a scientific writer, Ana is passionate about bridging the gap between research and real-world impact. With expertise in immunology, virology, oncology, and clinical studies, she makes complex science clear and accessible. Her mission: to accelerate knowledge sharing and empower evidence-based decisions