A study today in Science posits that a single genetic mutation that occurred in the Zika virus in 2013 allowed the mosquito-borne pathogen to become more infective and cause microcephaly and Guillain-Barre syndrome.
The work was done by researchers from the Chinese Academy of Sciences in Beijing. They compared Zika virus strains from the 2015 and 2016 South American epidemics with an ancestral Cambodian virus that was circulating in 2010.
According to the study, one change, known as S139N, which switched a serine to a glutamine at the 139th position of a structural protein within the pathogen's protective coat, made the virus deadlier to neuron precursor cells.
Evolution to congenital pathogen
To demonstrate if this change led to microcephaly and neurodegenerative changes to offspring exposed to the virus, the researchers used mouse models to simulate human pregnancy and Zika exposure. They infected mice on day 13 of pregnancy (which corresponds to the second trimester in human pregnancy) with strains from both the 2015-16 Zika virus and the 2010 virus. By day 18, fetuses of the mice infected with the 2015-16 strain showed severe microcephaly and thinning of the cortex.
"Our findings offer an explanation for the unexpected causal link of ZIKV [Zika virus] to microcephaly, and will help understand how ZIKV evolved from an innocuous mosquito-borne virus into a congenital pathogen with global impact," the authors concluded.
The small study "makes sense" to infectious disease expert Michael Osterholm, PhD, MPH. He is director of the University of Minnesota's Center for Infectious Disease Research and Policy, publisher of CIDRAP News, but he cautioned that the results need to be replicated and confirmed.
"We know that Zika did not cause microcephaly or neurological problems until 2014 or so," Osterholm. "So the only conclusion is either people changed or the virus changed."
The Zika virus was first identified in Uganda in 1947, but it caused only sporadic outbreaks of mild to moderate illness in humans until 2014, when a large outbreak occurred in French Polynesia.
In 2015, the virus began spreading in Brazil, where infants born with congenitally small heads and brains were soon seen in maternity wards. Several different hypotheses have been used to explain the phenomenon, including co-infection with other flaviviruses, such as chikungunya.
Study shows true danger of virus
More than anything, Osterholm said the proof of a potentially dangerous genetic mutation shows that Zika virus is to be feared.
"What this study really means is that if you have an area with a Zika outbreak in 2013 or 2014, the Zika you see in 2017 could be a different virus," said Osterholm. "The speed at which mutation changes in the virus occur completely change the public health impact of the virus."
Still, Osterholm cautioned that the mouse model used in the study did not show any placental involvement, which is necessary to show a congenital infection.
"But it makes epidemiological sense that something in the virus changes to cause microcephaly," Osterholm said. "From that standpoint it's not surprising."
See also:
Sep 28 Science study
