Chikungunya Virus’s ‘Invisibility Shield’: A Novel Mechanism of Cell-To-Cell Spread

Chikungunya fever is a mosquito-borne disease that causes severe and often chronic joint pain, fever, rash, and headache.

The disease is caused by the chikungunya virus, which is transmitted to humans by the bite of infected mosquitoes. There is currently no vaccine or antiviral drug to prevent or treat chikungunya infection.

However, a recent study by researchers at the Albert Einstein College of Medicine has revealed a new mechanism by which the virus can evade the host's immune system and spread from cell to cell.

This discovery may pave the way for developing effective vaccines or treatments for this emerging and debilitating disease.

How the chikungunya virus uses an 'invisibility shield' to escape antibodies

(Photo : OLIVIER MORIN/AFP via Getty Images)

The study, published in Nature Microbiology, showed that the chikungunya virus can hijack the host cell's cytoskeleton, which is a network of proteins that support the cell's shape and movement.

The virus induces the infected cell to form long thin extensions, called intercellular long extensions (ILEs), that reach out and make contact with neighboring uninfected cells.

The virus then uses these ILEs as bridges to transfer infectious particles from cell to cell, without exposing them to the bloodstream where antibodies are present.

The researchers named this mode of viral transmission cell-to-cell transmission, and contrasted it with the conventional mode of viral transmission, where the virus infects a cell, replicates within it, and then releases new copies of the virus into the bloodstream that can infect new cells.

The researchers found that cell-to-cell transmission was more efficient and faster than conventional transmission and that it allowed the virus to avoid being neutralized by antibodies.

The researchers also confirmed their findings in vivo, using a mouse model of chikungunya infection.

They showed that mice infected with the chikungunya virus that expressed a fluorescent reporter protein had more ILEs in their tissues than mice infected with a control virus that did not express the reporter protein.

They also showed that mice treated with antibodies that could block conventional transmission had lower viral loads in their blood than untreated mice, but had similar viral loads in their tissues, suggesting that cell-to-cell transmission was still occurring.

Also Read: Dengue, Zika, and Chikungunya: The Triple Threat of Co-Infections by Mosquito-Borne Viruses

Implications for vaccine and treatment development

The discovery of the chikungunya virus's 'invisibility shield' may have important implications for vaccine and treatment development.

For example, vaccines that target the surface proteins of the virus may not be effective enough to prevent or clear infection, since the virus can hide some of its copies inside ILEs.

Therefore, vaccines that can elicit strong cellular immunity, such as T cells, may be more desirable. Alternatively, drugs that can inhibit the formation or function of ILEs may be useful to block cell-to-cell transmission and reduce viral spread.

The study also provides new insights into the pathogenesis and persistence of chikungunya infection.

The researchers speculated that cell-to-cell transmission may contribute to the chronic and recurrent symptoms of chikungunya fever, such as arthritis, by allowing the virus to maintain a reservoir of infection in the tissues.

Moreover, cell-to-cell transmission may facilitate viral evolution and adaptation, by increasing the genetic diversity and recombination of viral populations.

The study also raises the possibility that other viruses may use similar strategies to evade immune detection and enhance viral dissemination.

The researchers noted that some viruses, such as HIV and herpes simplex virus, have been shown to use cellular extensions to spread from cell to cell.

Therefore, further research on this novel mechanism of viral transmission may have broad implications for understanding and combating viral diseases.

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