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Emory Researchers Study Zika Virus Infection in Human Dendritic Cells

FEB 15, 2017 | SARAH ANWAR
Researchers from Emory University believe that they’ve identified a therapy target to boost human immunity against infection with the Zika virus.
 
In late July of last year, the first four in a string of cases of locally-acquired Zika virus infections were identified to be residents of Miami-Dade County, Florida. Four months later, Texas claimed the title of second US state with local Zika transmission. Thus far, there has been a total of 236 locally-acquired cases in four Florida counties, and six locally-acquired cases in Cameron County, Texas.
 
With the Zika virus already circulating in some US states and mosquito season on the horizon, identifying a means to block Zika virus infection has become even more important.
 
In a study published in the journal PLOS Pathogens, a group of researchers from Emory Vaccine Center at Emory University discussed their analysis of the “early innate immune response” human dendritic cells had to infection with the Zika virus. To do this, the researchers studied how viral infection differed when these cells were infected with the Puerto Rican strain (PR-201) of the Zika virus versus when infected with isolates from the historic African (MR-1947 and Dak-1984) and Asian (P6-1966) strains.
 
According to the study, dendritic cells are vital to immune response in that they can identify pathogens and activate “innate and adaptive antiviral immunity.” Nevertheless, infection with each of the strains of the Zika virus used in this study prevented type I interferon (IFN) protein translation, thus inhibiting antiviral effects.
 
Both RIG-I-like receptors and type I IFN signaling axis work to fight flavivirus infections by blocking viral replication. However, unlike other flaviviruses, Zika was found to target STAT2 proteins. Although it is known that Zika inhibits interferon signaling, the researchers discovered that when dendritic cells were treated with retinoic acid-inducible gene I (RIG-I) agonists, the cells were able to obstruct viral replication. Human dendritic cells were found to be susceptible to infection by contemporary as well as historical forms of the Zika virus. As for infection with the historical isolates, in both MR-1947 and Dak-1984 strains the virus was observed to multiply faster within the cells as well as cause “higher infection magnitude” and cell death when compared to the P6-1966 strain. The researchers reported “minimal up-regulation” of human dendritic cell “activation markers and pro-inflammatory cytokine secretion,” during infection with either of the strains.
 
In addition, the researchers found that the Zika virus also interfered with “type I IFN-mediated phosphorylation of STAT1 and STAT2.”
 
Commenting on the study in a press release, Mehul Suthar, PhD, assistant professor of pediatrics at Emory University School of Medicine and Emory Vaccine Center, said, “How Zika blocks translation of type I interferon is unknown and studies are underway to understand the mechanism behind this unique finding.” The researchers believe that the Zika virus targets additional pathways in these cells that have yet to be identified, but they are working to do so.
 
The researchers concluded in their study, “Combined, our findings show that ZIKV subverts DC immunogenicity during infection, in part through evasion of type I IFN responses, but that the [RIG-I-like receptor] signaling pathway is still capable of inducing an antiviral state, and therefore may serve as an antiviral therapeutic target.”
 
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