Zika Fetal Neuropathogenesis: Etiology of a Viral Syndrome

Abstract

The ongoing Zika virus epidemic in the Americas and the observed association with both fetal abnormalities (primary microcephaly) and adult autoimmune pathology (Guillain–Barré syndrome) has brought attention to this neglected pathogen. While initial case studies generated significant interest in the Zika virus outbreak, larger prospective epidemiology and basic virology studies examining the mechanisms of Zika viral infection and associated pathophysiology are only now starting to be published. In this review, we analyze Zika fetal neuropathogenesis from a comparative pathology perspective, using the historic metaphor of “TORCH” viral pathogenesis to provide context. By drawing parallels to other viral infections of the fetus, we identify common themes and mechanisms that may illuminate the observed pathology. The existing data on the susceptibility of various cells to both Zika and other flavivirus infections are summarized. Finally, we highlight relevant aspects of the known molecular mechanisms of flavivirus replication.

Pregnancy, the placenta and Zika virus (ZIKV) infection

“…This is presumed to result in the microcephalic phenotype via neuronal cell death 16 . This is consistent with observations that African ZIKV strains infect neural precursor cells in murine models (summarised in Klase et al 17 ).…”

Congenital Human Cytomegalovirus Infection and the Enigma of Maternal Immunity

“…More recently, the description of the Zika virus outbreak in Brazil significantly increased awareness of the potential of intrauterine viral infections to lead to severe central nervous system (CNS) damage (3)(4)(5)(6). Fortunately, results from nearly 5 decades of natural history studies of congenital HCMV infections have provided a roadmap for studies of the consequences of Zika virus infections that occur during pregnancy.…”

Prevalence of Antibodies to Zika Virus in Mothers from Hawaii Who Delivered Babies with and without Microcephaly between 2009-2012

“…Mosquitoes of the Aedes genus transmit ZIKV. Approximately 80% of individuals infected with ZIKV have no symptoms [1, 2]. ZIKV caused only sporadic cases of infection in Africa and Southeast Asia until 2007, when the first large outbreak occurred in the Yap State in Micronesia [3, 4].…”

“…In 2015, the virus was first reported in Brazil and since then has spread through several additional countries in South and Central America and the Caribbean. Simultaneously, several of these countries have seen a dramatic increase in the incidence of infants born with microcephaly [1, 2, 8]. Since then ZIKV outbreaks have been recorded in the United States and Hawaii has encountered few cases of travel related ZIKV [9–11].…”