” However, weve found that the virus can likewise hijack a host cells cytoskeleton– the proteins that support cells and preserve their shape. The infection triggers the contaminated cell to send long thin extensions that reach uninfected neighboring cells, allowing the virus to safely and efficiently travel from one cell to another.”
Dr. Kielian and her coworkers have actually called these virus-induced structures intercellular long extensions, or ILEs. “This mode of viral transmission might not just shield some copies of the virus from the hosts immune action, but it might also explain why signs of chikungunya infection can continue for lots of months or years,” added very first author Peiqi Yin, Ph.D., a postdoctoral fellow in Dr. Kielians laboratory.
The infection is spread to humans by the bite of contaminated mosquitoes, which end up being infected by feeding on people who currently have the virus. The National Institute of Allergy and Infectious Diseases lists chikungunya infection as a Category B Pathogen, the second-highest concern for organisms positioning risks to nationwide security and public health.
Confirming a Cell Structures Role
Dr. Kielian and coworkers found the existence of ILEs in chikungunya-infected cells a number of years earlier, however it wasnt clear whether the structures facilitated cell-to-cell viral transmission. The study explained in the Nature Microbiology paper was developed to answer that question.
The first part of the study involved making use of cultured mouse cells. The scientists exposed the cells to chikungunya infection that expressed a fluorescent press reporter protein, enabling them to observe that infectious infection particles were indeed being sent from cell to cell via ILEs. Cell-to-cell transmission took place even in the presence of high quantities of reducing the effects of antibodies that were contributed to the culture medium.
To verify this mode of cell-to-cell transmission in living animals, the scientists studied chikungunya infection in mice. Mice that were first inoculated with neutralizing antibodies and were then directly injected with chikungunya infection did not end up being contaminated. Antibody-treated mice that were then injected with virus-infected cells (rather than simply the virus) did develop chikungunya infections that were resistant to the neutralizing antibodies.
” Together, these studies reveal that ILEs protect chikungunya infection from neutralizing antibodies and promote intercellular virus transmission, both in vitro and in vivo,” stated Dr. Yin. The mouse research studies were performed by Thomas E. Morrison, Ph.D., and his group at the University of Colorado School of Medicine in Aurora.
Short-Circuiting the Connections
In a last set of studies, the scientists determined that certain antiviral antibodies were able to obstruct ILEs from forming and to prevent cell-to-cell transmission. “If we can generate the production of such antibodies in human clients, or establish other approaches to stop ILE development, that could be specifically practical in fighting the persistent signs of chikungunya infection,” stated Dr. Kielian. “Were currently studying different ways to do this.”
Referral: “Chikungunya infection cell-to-cell transmission is mediated by intercellular extensions in vitro and in vivo” by Peiqi Yin, Bennett J. Davenport, Judy J. Wan, Arthur S. Kim, Michael S. Diamond, Brian C. Ware, Karen Tong, Thérèse Couderc, Marc Lecuit, Jonathan R. Lai, Thomas E. Morrison and Margaret Kielian, 17 August 2023, Nature Microbiology.DOI: 10.1038/ s41564-023-01449-0.
The research was supported by grants from the National Institutes of Health and by an NCI Cancer Center Support Grant.
Contending interests: Dr. Lai is a paid specialist for Celdara Medical, LLC. Dr. Diamond is a consultant for Inbios, Vir Biotechnology, Senda Biosciences, Ocugen, Moderna, and Immunome.
The infection is spread to people by the bite of contaminated mosquitoes, which become infected by feeding on individuals who currently have the virus. The National Institute of Allergy and Infectious Diseases lists chikungunya infection as a Category B Pathogen, the second-highest priority for organisms posturing risks to nationwide security and public health.
The researchers exposed the cells to chikungunya infection that revealed a fluorescent reporter protein, enabling them to observe that transmittable infection particles were indeed being transferred from cell to cell via ILEs. Mice that were very first inoculated with reducing the effects of antibodies and were then directly injected with chikungunya infection did not become infected. Antibody-treated mice that were then injected with virus-infected cells (rather than just the infection) did establish chikungunya infections that were resistant to the neutralizing antibodies.
Researchers have actually discovered that the chikungunya virus can transfer directly from one cell to another through structures called intercellular long extensions (ILEs). This discovery might discuss the viruss durability versus antibodies and could lead the way for brand-new treatments.
The virus restructures infected cells to protect versus antibody attacks.
Researchers at the Albert Einstein College of Medicine have discovered that the virus causing chikungunya fever can spread out directly from cell to cell– perhaps fixing the longstanding secret of how the infection, now becoming a major health risk, can manage to escape antibodies distributing in the bloodstream.
The findings, recently released in the journal Nature Microbiology, suggest possible paths for the production of vaccines or treatments against chikungunya fever, a debilitating and progressively typical mosquito-borne illness.
A Possible Explanation for Prolonged Infections
” Previously, chikungunya virus was believed to spread in the body by infecting a cell, duplicating within that cell, and then sending new copies of the virus into the bloodstream that then contaminate new cells,” said research study leader Margaret Kielian, Ph.D., professor of cell biology and the Samuel H. Golding Chair in Microbiology at Einstein.
