May 17, 2018

Alphavirus “Achilles heel”

Targeting the protein that mosquito-borne viruses use to enter cells could be a strategy for preventing infection by multiple emerging viruses.

Some mosquito-borne pathogens called alphaviruses, including the chikungunya virus that recently was associated with a large outbreak in the Caribbean, can cause debilitating acute and chronic musculoskeletal disease. It has not been clear how these viruses attach to human cells to initiate infection.

Now a collaborative group led by investigators at Washington University in St. Louis has identified the cell adhesion molecule Mxra8, expressed by many cells in the body, as an entry mediator for “arthritogenic” alphaviruses that cause arthritis including chikungunya, Ross River (Australia), Mayaro (South America), and O’nyong nyong (Africa).

Co-author James Crowe Jr., MD, and colleagues at Vanderbilt made human monoclonal antibodies from chikungunya survivors that captured virus particles, added a fusion protein linked to the Mxra8 receptor in an assay, and showed that Mxra8 binds directly to the virus.

The group’s report, published May 16 in the journal Nature, suggests that targeting Mxra8 could be a strategy for preventing infection and disease caused by multiple emerging alphaviruses.

This research was supported by the National Institutes of Health (grants AI114816, AI123348, AI095436, contract HHSN272201400058C) and the Defense Reduction Threat Agency.

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