Animal study hints at Zika damage potential in adult brains

lab mouse
lab mouse

lculig/ iStock

Zika virus can infect developing nerve cells in adults, but it's unclear what the clinical impact might be, according to a mouse experiment that suggests that the unique damage from the disease may not be limited to developing fetuses.

In other research developments, new findings today revealed a role for certain placental cells in fetal Zika infections, and a report from Brazil yesterday highlighted the transmission risk from platelet transfusion.

Virus shows affinity for adult neural stem cells

Zika illness is thought to be mild for most adults, and only about 20% of those infected show symptoms. Guillain-Barre syndrome (GBS) is a known complication of Zika and other viral infections, though reports are rare. Over the past several months, clinicians have reported other possibly related complications in teens and adults, including meningitis and myelitis.

Researchers based at Rockefeller University and La Jolla Institute of Allergy and Immunology published results from their experiments with Zika virus in mice today in Cell Stem Cell. Though mice resist Zika infection, scientists have developed a genetically modified type that is susceptible to help them study the impact of the virus.

They focused on neural stems cells, which studies have already shown to be vulnerable to Zika virus in newborns and a likely factor in the damage that leads to microcephaly. Neural stem cells are found in limited parts of adult brains, and in mice are found in two areas: the subventricular part of the anterior forebrain and the subgranular part of the hippocampus.

Three days after the researchers injected the virus into the mice's bloodstreams, they harvested the brains and used antibodies to identify presence of Zika virus. They found viral particles surrounding the neural stem cells, with evidence of cell death and a drop in replication.

Sujan Shresta, PhD, study coauthor and an infectious disease researcher at La Jolla Institute of Allergy and Immunology, said in a press release from Cell Press, the journal's publisher, that adult neurogenesis is involved with learning and memory. "We don't know what this would mean in terms of human diseases, or if cognitive behaviors of an individual could be impacted after infection," she said.

The group said the next step in the investigation is to look at changes in neural stem cell populations in the infected adult mice over time and to see if patterns vary with a different Zika virus strain.

Experiments tag placental cells vulnerable to Zika

Another study today shed more light on how Zika virus passes through the placenta of infected pregnant women to their fetuses. Researchers found that two of the three types of placental cells they studied—fibroblasts and Hofbauer cells—were susceptible to infection in lab culture experiments.

The authors, based at Yale University, published their findings today in the Journal of Clinical Investigation (JCI) Insight.

Cells used in the study were from normal-term human pregnancies and also included cytotrophoblasts. Researchers used three different Zika strains to see if the cells were susceptible to infection: a 1947 African strain, a 2010 Asian strain, and a 2016 isolate from Mexico.

Cell studies not only showed that fibroblasts and Hofbauer cells were susceptible, but also suggested that Hofbauer cells within whole placental samples could be infected.

Kellie Ann Jurado, PhD, a postdoctoral fellow who was part of the research group, said in a Yale University press release, "These placenta-specific cells could potentially serve as a reservoir for Zika virus production within the fetal compartment."

The researchers added that Hofbauer cells are thought to migrate around the placenta, which could facilitate passing the virus to the fetal brain. They also said the findings might help investigators design strategies to prevent fetal infections.

Zika transmission from platelet transfusion

In another medical literature development, Brazilian clinicians yesterday reported two cases of likely Zika transmission related to a person who donated platelets while asymptomatic. The group reported its findings yesterday in a letter to the New England Journal of Medicine.

In March, Brazilian officials reported two blood transfusion-related Zika infections, and in Puerto Rico, Zika detected in blood center screening in June was one of the early markers for a rapid rise in disease activity.

The patients who contracted the virus were a 54-year-old woman with myelofibrosis syndrome and a 14-year-old girl with acute myeloid leukemia who had undergone a bone marrow transplant and was receiving immunosuppressive treatment.

Pretransfusion tests on the patients had been negative for Zika and other mosquito-borne viruses.

Neither of the patients had clinical symptoms of Zika, but repeat tests done 6 days after transfusion in the woman and 23 to 51 days after transfusion in the girls revealed evidence of Zika infection. Genetic sequencing confirmed the connection between Zika in the donor and the platelet recipients. 

See also:

Aug 18 Cell Stem Cell abstract

Aug 18 Cell Press media release

Aug 18 JCI Insight abstract

Aug 18 Yale University press release

Aug 17 N Engl J Med letter

This week's top reads