Abstract
Since the explosive outbreak of Zika virus in Brazil and South/Central America in 2015–2016, the frequency of infections has subsided, but Zika virus remains present in this region as well as other tropical and sub-tropical areas of the globe. The most alarming aspect of Zika virus infection is its association with severe birth defects when infection occurs in pregnant women. Understanding the mechanism of Zika virus pathogenesis, which comprises features unique to Zika virus as well as shared with other teratogenic pathogens, is key to future prophylactic or therapeutic interventions. Nonhuman primate-based research has played a significant role in advancing our knowledge of Zika virus pathogenesis, especially with regard to fetal infection. This review summarizes what we have learned from these models and potential future research directions.
Highlights
Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Department of Pathology, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd, Division of Pathobiology & Immunology, Oregon National Primate Research Center, 505 NW 185th Ave, Beaverton, OR 97006, USA
Transplacental infection occurs with primary infection of the mother; while transmission to the fetus is more common later in gestation, it is more severe in early gestation
Transplacental infection is most common in untreated secondary syphilis
Summary
Zika virus (ZIKV) is a mosquito-borne flavivirus that emerged as a major public health threat in South and Central America in 2015–2016. Large outbreaks (in what were presumably immunologically naïve populations) were detected on the Micronesian island of Yap in 2007, and in French Polynesia in 2013 These outbreaks preceded the introduction of the virus into Latin America in 2014–2015. CZS comprises a spectrum of phenotypes, ranging from congenital microcephaly to more subtle phenotypes that manifest later in life These include ocular and auditory abnormalities, cognitive and motor deficits, and seizures. Data from Rio de Janeiro, Brazil, described adverse outcomes from ZIKV infection in 46% of pregnancies [7], while data collected from the US and US territories show an adverse outcome rate of 5–14% [13,14]. It is possible that the full impact of the ZIKV outbreak will not be appreciated until those born to infected women approach adulthood
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