Zika Virus Directly Infects Brain Cells, Evades Immune Detection

Zika, the mosquito-borne virus linked to microcephaly and other neurological problems in newborns of affected mothers, directly infects the brain progenitor cells destined to become neurons, UT Southwestern Medical Center researchers report in a new study.

The research team used a strain of Zika virus currently impacting the Americas, and found that the virus infects about 20 percent of cells on average, evades immune system detection, and continues to replicate for weeks.

Senior author Dr. John Schoggins, Assistant Professor of Microbiology at UT Southwestern, said:

“The cellular system we studied mirrors what pathologists are finding in the brain tissue of affected infants and will be valuable for further understanding how Zika causes severe brain-related problems. The system may also serve as a platform for testing new therapies targeting the virus.”

Zika can be spread either by infected mosquitos or through sexual intercourse.

In adults, the symptoms are generally mild and include fever, rash, joint pain, and red eyes. However, Zika virus can cause a serious birth defect called microcephaly, and other severe neurological effects such as eye problems, hearing loss, and impaired growth in infants born to women who contracted the virus when pregnant, according to the Centers for Disease Control and Prevention (CDC).

The CDC’s website lists a series of unanswered questions about the virus that the World Health Organization (WHO) has declared a public health emergency of international concern.
The unanswered questions include:

If a pregnant woman is exposed

  • We don’t know how likely she is to get Zika.

If a pregnant woman is infected

  • We don’t know how the virus will affect her or her pregnancy.
  • We don’t know how likely it is that Zika will pass to her fetus.
  • We don’t know if the fetus is infected, if the fetus will develop birth defects
  • We don’t know when in pregnancy the infection might cause harm to the fetus.
  • We don’t know whether her baby will have birth defects.
  • We don’t know if sexual transmission of Zika virus poses a different risk of birth defects than mosquito-borne transmission.

Said Dr. Schoggins, a Nancy Cain and Jeffrey A. Marcus Scholar in Medical Research, in Honor of Dr. Bill S. Vowell:

“There was a suggestion that the detrimental effects of the virus might be linked to its ability to infect brain cells, specifically the progenitor cells that give rise to neurons.

We showed that neural progenitors can be infected by a strain of Zika virus that is currently infecting people in the Americas,” Dr. Schoggins said. “We found that the virus kills some neural progenitor cells, but not all. Other cells survive the infection, and surprisingly, continue to replicate the virus for many weeks. In addition, it appears that Zika virus does not stimulate much of an immune response.”

Recent media reports have suggested that a pesticide called pyriproxyfen might be linked with microcephaly. Pyriproxyfen has been approved for the control of disease-carrying mosquitoes by the World Health Organization.

Pyriproxyfen is a registered pesticide in Brazil and other countries, it has been used for decades, and it has not been linked with microcephaly. In addition, exposure to pyriproxyfen would not explain recent study results showing the presence of Zika virus in the brains of babies born with microcephaly.

Natasha W. Hanners, Jennifer L. Eitson, Noriyoshi Usui, R. Blake Richardson, Eric M. Wexler, Genevieve Konopka, John W. Schoggins
Western Zika Virus in Human Fetal Neural Progenitors Persists Long Term with Partial Cytopathic and Limited Immunogenic Effects
Cell Reports, 2016; DOI: 10.1016/j.celrep.2016.05.075

Image: 3D representation of a Zika virus. By Manuel Almagro Rivas CC BY-SA 4.0

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