At the American Association for the Advancement of Science meeting in Boston last weekend, Emory Vaccine Center researcher Mark Mulligan presented some limited findings on immune responses in Zika-infected humans, who were returned US travelers or expatriates.
The results were intriguing, despite the small number of study participants: five, two of whom were pregnant. Detailed information has not been available about immune responses against Zika in humans, especially T cell responses.
Highlights from Mulligan’s abstract:
*All five seemed to have a hole in their immune systems – functional antiviral “killer” CD8 T cells were rare, despite activation of CD8 T cells in general and strong responses from other cell types.
*Cross-reactive immune responses, based on previous exposure to dengue and/or yellow fever vaccine, may have blunted Zika’s peak.
*”Even with prolonged maternal viremia, both pregnancies resulted in live births of apparently healthy babies.” Read more
Important immune alarm cells — dendritic 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.
Mehul Suthar, PhD in the lab with graduate students Kendra Quicke and James Bowen
The findings were published 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. Read more
Zika virus can infect and replicate in immune cells from the placenta, without killing them, scientists have discovered. The finding may explain how the virus can pass through the placenta of a pregnant woman, on its way to infect developing brain cells in her fetus.
Infected placental macrophages. Zika antigens visible in red. From Quicke et al (2016).
The results were published in Cell Host & Microbe.
“Our results substantiate the limited evidence from pathology case reports,” says senior author Mehul Suthar, PhD, assistant professor of pediatrics at Emory University School of Medicine. “It was known that the virus was getting into the placenta. But little was known about where the virus was replicating and in what cell type.”
Scientists led by Suthar and Emory pediatric infectious disease specialist Rana Chakraborty, MD, found that Zika virus could infect placental macrophages, called Hofbauer cells, in cell culture. The virus could also infect another type of placental cell, called cytotrophoblasts, but only after a couple days delay and not as readily. Other researchers recently reported that syncytiotrophoblasts, a more differentiated type of placental cell than cytotrophoblasts, are resistant to Zika infection.
The cells for the experiments were derived from full-term placentae, obtained from healthy volunteers who delivered by Cesarean section. The level of viral replication varied markedly from donor to donor, which hints that some women’s placentae may be more susceptible to viral infection than others. Read more