Tracing Zika's Genetic History

NIAID Now | August 28, 2019

Zika virus particles (red) shown in African green monkey kidney cells

Credit: NIAID

The Zika virus genome, like that of most viruses, is tiny: 10,623 nucleotides, compared to the human genome’s 3 billion. As small as this might seem, the Zika virus genome contains all the instructions the virus needs to infect human tissues, make copies of itself, and be carried to another human host by a mosquito. As the virus is transmitted from person to person by a mosquito, its genome may develop random mutations, which then persist in subsequent infections. By studying the accumulated mutations of a virus and comparing them to other viral samples collected from many different locations and periods of time, scientists can retrace the path that a disease took as it spread through new populations. These data can even reveal previously undiscovered outbreaks and provide insight that public health officials can use to stop future pandemics.

For instance, in a new paper published in Cell, NIAID-funded researchers used a combination of travel surveillance and genomic sequencing to uncover a previously unreported outbreak of Zika virus in Cuba. Zika virus disease can be difficult to detect as most people do not have symptoms or have mild, nonspecific symptoms, such as fever or rash. When a pregnant woman is infected, the virus can cause congenital Zika syndrome, potentially leading to stillbirth, birth abnormalities, such as microcephaly, and developmental delays. Until severe symptoms like these are reported to public health authorities, Zika virus can spread unnoticed.

While studying reported cases of Zika associated with travelers that returned from the Caribbean to the U.S. or Europe between June 2017 and October 2018, the researchers found that in more than 98% of cases (153 out of 155 cases that the research team studied during this period), the travelers had visited Cuba. Most of Cuba’s neighboring countries had already seen their Zika outbreaks fade by this time—the peak of new Zika infections in the Caribbean occurred between 2016 and 2017. This suggested that Cuba had experienced an undetected Zika outbreak in 2017-2018, which was occurring several months after nearby countries’ outbreaks had ended.

To see where this outbreak could have come from, the researchers also sequenced Zika genomes from nine infected people who arrived in Florida after travelling to Cuba. The viral genomes revealed that the Zika virus had likely come to Cuba at least three times from other areas in the Caribbean, and at least once from Central America. A vector control campaign in Cuba, the researchers say, contributed in part to the delay in the outbreak.

Since 2018, large outbreaks of Zika have ended, and the virus no longer dominates the headlines. However, by retracing its path, researchers can provide healthcare providers and epidemiologists with maps of Zika’s spread that may be valuable for spotting future outbreaks. For instance, another study by many of the same NIAID-funded researchers, published in Nature in 2017, compared the genomes of 39 ZIKV samples to those of  65 samples they had previously sequenced, and discovered that the Zika virus had been introduced to Florida at least four separate times before experiencing limited local spread. Moreover, they believed, the first outbreak could have circulated in Florida for up to three months before first being detected in July 2016. Another NIAID-supported study with some of the same authors, also published in Nature in 2017, used 174 individual Zika genomes to make a map of the virus as it spread through Central and South America, again finding that the virus was introduced to each region months before the first cases were reported.

These studies highlight a disquieting facet of the Zika virus: it can circulate undetected with ease. In fact, the authors of the Cell paper note that significant transmission of Zika virus in the Americas could still be ongoing, undetected by surveillance networks. By learning more about how similar viruses act and spread, global health organizations may be able improve disease surveillance networks, so that if Zika or a similar virus resurges again, healthcare providers will be able to more rapidly detect and respond to cases.


ND Grubaugh et alTravel surveillance and genomics uncover a hidden Zika outbreak during the waning epidemic.Cell DOI: 10.1016/j.cell.2019.07.018 (2019)

ND Grubaugh et alGenomic epidemiology reveals multiple introductions of Zika virus into the United States. Nature DOI: 10.1038/nature22400 (2017)

HC Metsky et al. Zika virus evolution and spread in the Americas. Nature DOI: 10.1038/nature22402 (2017)

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