NIH-funded researchers identify target for chikungunya treatment
Female (left) and male (right) Aedes aegypti mosquitoes. Female A. aegypti mosquitoes can carry chikungunya virus.NIAID
Scientists have identified a molecule found on human cells and some animal cells that could be a useful target for drugs against chikungunya virus infection and related diseases, according to new research published in the journal Nature. A team led by scientists at Washington University School of Medicine in St. Louis conducted the research, which was funded in part by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.
Chikungunya, an alphavirus, is transmitted to humans by the bite of an infected mosquito. Currently no specific treatment is available for chikungunya virus infection, which can cause fever and debilitating joint pain and arthritis. Small, sporadic outbreaks of chikungunya occurred in Africa, Asia, Europe, and the Indian and Pacific Oceans after the virus was identified in the 1950s. In 2013, the virus spread to the Americas and has since caused a widespread and ongoing epidemic.
In this study, scientists aimed to better understand which traits make humans susceptible to chikungunya virus infection. Using the gene-editing tool CRISPR-Cas9, they performed a genome-wide screen that identified the molecule Mxra8 as a key to the entry of chikungunya virus and related viruses into host cells. In the laboratory, scientists were able to reduce the ability of chikungunya virus to infect cells by editing the human and mouse genes that encode Mxra8. The researchers also administered anti-Mxra8 antibodies to mice and infected the mice with chikungunya virus or O’nyong-nyong virus, another alphavirus. The antibody-treated mice had significantly lower levels of virus infection and related foot swelling as compared with a control group.
These findings, along with future studies to better understand how chikungunya virus interacts with Mxra8, could help inform development of drugs to treat diseases caused by alphaviruses, according to the authors.
R Zhang et al. Mxra8 is a receptor for multiple arthritogenic alphaviruses. Nature DOI: 10.1038/s41586-018-0121-3 (2018).
NIAID Director Anthony S. Fauci, M.D., is available for comment. Patricia M. Repik, Ph.D., program officer for Emerging Viral Diseases in the Virology Branch of NIAID’s Division of Microbiology and Infectious Diseases, is also available for comment.
This press release describes a basic research finding. Basic research increases our understanding of human behavior and biology, which is foundational to advancing new and better ways to prevent, diagnose, and treat disease. Science is an unpredictable and incremental process — each research advance builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without the knowledge of fundamental basic research.
NIAID conducts and supports research — at NIH, throughout the United States, and worldwide — to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
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