Zika Virus Pathogenesis: From Early Case Reports to Epidemics

Abstract

For the first 60 years following its isolation, Zika virus (ZIKV) remained a relatively poorly described member of the Flaviviridae family. However, since 2007, it has caused a series of increasingly severe outbreaks and is now associated with neurological symptoms such as Guillain-Barré syndrome and congenital Zika syndrome (CZS). A number of reports have improved our understanding of rare complications that may be associated with ZIKV infection in adults, the areas of the body to which it spreads, and viral persistence in various tissues. Likewise, studies on the effect of ZIKV infection during pregnancy have identified risk factors for CZS and the impact this syndrome has on early childhood. Understanding these outcomes and the factors that drive ZIKV pathogenesis are key to developing vaccination and therapeutic approaches to avoid these severe and potentially debilitating symptoms.

Keywords: Guillain-Barré syndrome; Zika virus; congenital Zika syndrome; fetal microcephaly; pathogenesis.

Figure 1

Novel aspects of contemporary Zika virus (ZIKV) outbreaks. Recent ZIKV outbreaks have highlighted the novel epidemic capacity of the virus. Furthermore, ZIKV has been shown to disseminate to many sites throughout the body and ZIKV RNA has been persistently detected long after infection in semen and in the vaginal tract. Most strikingly, ZIKV has been associated with Guillain-Barré syndrome and congenital Zika syndrome (CZS), with impacts on neurodevelopment occurring even in the absence of symptoms like fetal microcephaly. The risk for CZS is increased when infection occurs early during pregnancy. Abbreviations: CSF, cerebrospinal fluid; CZS, congenital Zika syndrome; ZIKV, Zika virus.