Gatekeeper immune cells are fighting Zika virus with an arm tied behind their backs, scientists from Emory Vaccine Center report.
Dendritic cells are "sentinel" cells that alert the rest of the immune system when they detect viral infection. When Zika virus infects them, it shuts down interferon signaling, one route for mustering the antiviral troops. However, another antiviral pathway called RIG-I-like receptor (RLR) signaling is left intact and could be a target for immunity-boosting therapies, the researchers say.
The findings are scheduled for publication on Feb. 2 in PLOS Pathogens.
Zika was known to disrupt interferon signaling, but Emory researchers have observed that it does so in ways that are distinct from other related flaviviruses, such as Dengue virus and West Nile virus. The findings give additional insight into how Zika virus is able to counter human immune defenses.
"This is the first demonstration of a flavivirus actively blocking translation of type I interferon, a critical set of innate immune signaling proteins," says Mehul Suthar, PhD, assistant professor of pediatrics at Emory University School of Medicine and Emory Vaccine Center.
In addition, the researchers found that Zika blocks the phosphorylation of the immune regulatory proteins STAT1 and STAT2, which has not been previously reported.
The researchers studied a recently isolated Puerto Rican strain of Zika, as well as historic African and Asian strains. All of the tested Zika viruses blocked type I interferon signaling, suggesting a highly conserved mechanism amongst Zika viruses to inhibit dendritic cell antiviral responses.
Zika's stealthy infection of dendritic cells resembles its effects on other fetal and placental cell types, including findings from the authors' previous publication on placental macrophages.
"How Zika blocks translation of type I interferon is unknown and studies are underway to understand the mechanism behind this unique finding," Suthar says. The authors also suspect that Zika targets other immune pathways in dendritic cells in addition to interferon signaling and continue to investigate those.
Co-first authors of the paper are graduate students James R. Bowen and Kendra M. Quicke, who are in the Immunology and Molecular Pathogenesis and Microbiology and Molecular Genetics programs, respectively.
Bali Pulendran, PhD, and colleagues at Emory Vaccine Center, Yerkes National Primate Research Center contributed to the paper.
The research was supported by the National Institute of Allergy and Infectious Diseases (U19AI083019, R56AI110516, R21AI113485, 2U19AI090023, 5R37AI048638, 2U19AI057266), the National Institute of Diabetes and Digestive and Kidney Diseases (5R37DK057665), Children's Healthcare of Atlanta, Emory Vaccine Center and Georgia Research Alliance.
Source: Emory Health Sciences
CDC Urges Vigilance: New Recommendations for Monitoring and Testing H5N1 Exposures
July 11th 2025With avian influenza A(H5N1) infections surfacing in both animals and humans, the CDC has issued updated guidance calling for aggressive monitoring and targeted testing to contain the virus and protect public health.
IP LifeLine: Layoffs and the Evolving Job Market Landscape for Infection Preventionists
July 11th 2025Infection preventionists, once hailed as indispensable during the pandemic, now face a sobering reality: budget pressures, hiring freezes, and layoffs are reshaping the field, leaving many IPs worried about their future and questioning their value within health care organizations.
A Helping Hand: Innovative Approaches to Expanding Hand Hygiene Programs in Acute Care Settings
July 9th 2025Who knew candy, UV lights, and a college kid in scrubs could double hand hygiene adherence? A Pennsylvania hospital’s creative shake-up of its infection prevention program shows that sometimes it takes more than soap to get hands clean—and keep them that way.