Birth defects associated with Zika virus infection may depend on mother's immune response

August 14, 2019

New research led by scientists at The Rockefeller University in New York may help explain why Zika virus infection causes birth defects in some children but not others. The study, which will be published August 14 in the Journal of Experimental Medicine, suggests that the risk of developing an abnormally small head (microcephaly) depends on the types of antibody produced by pregnant mothers in response to Zika infection.

The Zika virus is spread by mosquitoes in tropical and subtropical regions, and, in most adults, the symptoms of infection are fairly mild. But the widespread Zika outbreak in Brazil in 2015-2016 revealed that infection during pregnancy can cause a wide range of fetal abnormalities, with microcephaly occurring in around 5% of live births by Zika-infected mothers. "Why some Zika virus-infected pregnant women deliver apparently healthy newborns while others have babies with microcephaly is unknown," says Davide F. Robbiani, a Research Associate Professor at The Rockefeller University, who co-led the study with Professor Michel C. Nussenzweig.

Various factors have been proposed to increase the risk of microcephaly, including previous exposure to viruses that are similar to Zika, such as dengue virus or West Nile virus. Antibodies generated by the body's immune system to combat these viruses may recognize the Zika virus but, instead of neutralizing it, help it to enter the mother's cells and possibly cross the placenta to infect the unborn fetus.

With the help of researchers and physicians in Brazil, Robbiani and colleagues analyzed blood samples collected during the 2015-2016 outbreak from Zika-infected mothers who had given birth to either healthy or microcephalic children.

Through a series of laboratory tests, the researchers saw no significant differences in the activity of antibodies produced against dengue or other Zika-related viruses, suggesting that prior exposure to these viruses does not increase the risk of Zika-associated birth defects.

However, when Robbiani and colleagues analyzed the activity of antibodies produced against the Zika virus itself, they saw several differences in the antibodies produced by the mothers of babies with microcephaly. Antibodies from these mothers were actually more effective at neutralizing the Zika virus than the antibodies produced by mothers of healthy newborns. Surprisingly, however, these antibodies also showed an enhanced ability to boost the entry of Zika virus into human cells grown in the laboratory.

The researchers confirmed their findings in macaques infected with the Zika virus. Pregnant monkeys that produced antibodies capable of enhancing the entry of Zika virus into cells were more at risk of giving birth to babies suffering from Zika-induced brain damage.

"Though our results only show a correlation at this point, they suggest that antibodies may be implicated in Zika fetal disease," Robbiani says. "Antibodies may exist that, instead of protecting, enhance the risk of Zika microcephaly, so the next step will be to figure out which antibodies are responsible for this, and how they promote fetal damage. This has significant implications for vaccine development; a safe Zika vaccine would have to selectively elicit antibodies that are protective, while avoiding those that potentially enhance the risk of microcephaly."
-end-
Robbiani et al., 2019. J. Exp. Med.http://jem.rupress.org/cgi/doi/10.1084/jem.20191061?PR

About the Journal of Experimental Medicine

The Journal of Experimental Medicine (JEM) features peer-reviewed research on immunology, cancer biology, stem cell biology, microbial pathogenesis, vascular biology, and neurobiology. All editorial decisions are made by research-active scientists in conjunction with in-house scientific editors. JEM makes all of its content free online no later than six months after publication. Established in 1896, JEM is published by Rockefeller University Press. For more information, visit jem.org.

Visit our Newsroom, and sign up for a weekly preview of articles to be published. Embargoed media alerts are for journalists only.

Follow JEM on Twitter at @JExpMed and @RockUPress.Funding Bodies

National Institutes of Health, The Rockefeller University Development Office, anonymous donors, Fundação de Amparo à Pesquisa do Estado da Bahia, National Institutes of Health Office of Research Infrastructure Programs/OD, United States Food and Drug Administration, DHHS/PHS, Conselho Nacional de Desenvolvimento Cientifico e Tecnológico, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Pew Latin American Fellows, Studienstiftung des Deutschen Volkes, Wellcome Trust, Howard Hughes Medical Institute

Grant numbers

5R01AI121207, R01TW009504, R25TW009338, U19AI111825, UL1TR001866, R01AI037526, UM1AI100663, U19AI111825, UL1TR001866, P01AI138938, R01AI124690, U19AI057229, PET0021/2016, R21AI129479-Supplement, P51OD011107, HHSF223201610542P, R01AI100989, R01AI133976, AI083019, AI104002, P51OD010425, R01Al116382-01A1, P51OD011106, RR15459-01, RR020141-01, P51 OD011092, R21-HD091032, R01-HD08633, 303999/2016-0, 439971/20016-0, 440405/2016-5

Rockefeller University Press

Related Science Articles from Brightsurf:

75 science societies urge the education department to base Title IX sexual harassment regulations on evidence and science
The American Educational Research Association (AERA) and the American Association for the Advancement of Science (AAAS) today led 75 scientific societies in submitting comments on the US Department of Education's proposed changes to Title IX regulations.

Science/Science Careers' survey ranks top biotech, biopharma, and pharma employers
The Science and Science Careers' 2018 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.

Science in the palm of your hand: How citizen science transforms passive learners
Citizen science projects can engage even children who previously were not interested in science.

Applied science may yield more translational research publications than basic science
While translational research can happen at any stage of the research process, a recent investigation of behavioral and social science research awards granted by the NIH between 2008 and 2014 revealed that applied science yielded a higher volume of translational research publications than basic science, according to a study published May 9, 2018 in the open-access journal PLOS ONE by Xueying Han from the Science and Technology Policy Institute, USA, and colleagues.

Prominent academics, including Salk's Thomas Albright, call for more science in forensic science
Six scientists who recently served on the National Commission on Forensic Science are calling on the scientific community at large to advocate for increased research and financial support of forensic science as well as the introduction of empirical testing requirements to ensure the validity of outcomes.

World Science Forum 2017 Jordan issues Science for Peace Declaration
On behalf of the coordinating organizations responsible for delivering the World Science Forum Jordan, the concluding Science for Peace Declaration issued at the Dead Sea represents a global call for action to science and society to build a future that promises greater equality, security and opportunity for all, and in which science plays an increasingly prominent role as an enabler of fair and sustainable development.

PETA science group promotes animal-free science at society of toxicology conference
The PETA International Science Consortium Ltd. is presenting two posters on animal-free methods for testing inhalation toxicity at the 56th annual Society of Toxicology (SOT) meeting March 12 to 16, 2017, in Baltimore, Maryland.

Citizen Science in the Digital Age: Rhetoric, Science and Public Engagement
James Wynn's timely investigation highlights scientific studies grounded in publicly gathered data and probes the rhetoric these studies employ.

Science/Science Careers' survey ranks top biotech, pharma, and biopharma employers
The Science and Science Careers' 2016 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.

Three natural science professors win TJ Park Science Fellowship
Professor Jung-Min Kee (Department of Chemistry, UNIST), Professor Kyudong Choi (Department of Mathematical Sciences, UNIST), and Professor Kwanpyo Kim (Department of Physics, UNIST) are the recipients of the Cheong-Am (TJ Park) Science Fellowship of the year 2016.

Read More: Science News and Science Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.