Researchers from the Albert Einstein College of Medicine announced in August that their publication in Nature Microbiology could help vaccine development for chikungunya fever. The team found that the virus behind the disease can spread “directly from cell to cell”, which could be the answer to the “longstanding mystery” of how it escapes antibodies circulating in the bloodstream. Chikungunya virus (CHIKV) has already caused “millions” of human infections worldwide. WHO states that, due to “challenges in reporting and diagnosis”, the real number of infections remains unknown.
Understanding the process
Study leader, Dr Margaret Kielian, professor of cell biology and Samuel H. Golding Chair in Microbiology suggests that previous understanding of the virus was that it infects a cell, replicates within that cell, and then sends “new copies” into the bloodstream to infect new cells.
“However, we’ve found that the virus can also hijack a host cell’s cytoskeleton – the proteins that support cells and maintain their shape.”
The virus manipulates the infected cell, causing it to send out “long, thin extensions” that connect with uninfected neighbouring cells and enable the virus to “safely and efficiently travel from one cell to another”. These structures are called intercellular long extensions (ILEs). First author Dr Peiqi Yin, gave insight into the effects of their role:
“This mode of viral transmission may not only shield some copies of the virus from the host’s immune system, but it may also explain why symptoms of chikungunya infection can persist for many months or years.”
ILEs reimagined in study
Although Dr Kielian and her team discovered ILEs in chikungunya-infected cells “several years ago”, they were unsure whether these structures supported cell-to-cell viral transmission. Therefore, they initiated the study. The first part involved the use of cultured mouse cells, which were exposed to chikungunya virus that expressed a fluorescent reporter protein. This allowed the researchers to see that infectious virus particles were being transmitted via ILEs. Even in the presence of high quantities of neutralising antibodies, cell-to-cell transmission took place.
To confirm that this mode of transmission takes place in living animals the team studied infection in mice. Mice that were inoculated with neutralising antibodies and then directly injected with the virus did not suffer infection. However, antibody-treated mice that were injected with virus-infected cells (instead of just virus), did develop infections that were resistant to the antibodies.
Finally, the researchers identified that certain antiviral antibodies were capable of blocking ILEs, thus preventing cell-to-cell transmission. Dr Kielian believes that the production of these antibodies in human patients, or the development of “other methods to stop ILE formation”, would be “helpful in combatting the chronic symptoms of chikungunya infection”. Therefore, the team are investigating this avenue.
Dr Yin states that the studies demonstrate that ILEs “shield” chikungunya virus from neutralising antibodies, promoting intercellular virus transmission. What does this mean for vaccine development?
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