Zika Virus Pathogenesis and Tissue Tropism

Abstract

Although Zika virus (ZIKV) was isolated approximately 70 years ago, few experimental studies had been published prior to 2016. The recent spread of ZIKV to countries in the Western Hemisphere is associated with reports of microcephaly, congenital malformations and Guillain-Barré syndrome. This has resulted in ZIKV being declared a public health emergency and has greatly accelerated the pace of ZIKV research and discovery. Within a short time period, useful mouse and non-human primate disease models have been established, and pre-clinical evaluation of therapeutics and vaccines has begun. Unexpectedly, ZIKV exhibits a broad tropism and persistence in body tissues and fluids, which contributes to the clinical manifestations and epidemiology that have been observed during the current epidemic. In this review, we highlight recent advances in our understanding of ZIKV pathogenesis, tissue tropism and the resulting pathology, and discuss areas for future investigation.

Extinction of Zika Virus and Usutu Virus by Lethal Mutagenesis Reveals Different Patterns of Sensitivity to Three Mutagenic Drugs

“…We deem that this study can stimulate an additional investigation on the therapeutic value of mutagenic drugs against flaviviruses and, in particular, for the treatment of persistent flaviviral disease (8, 81–83). Mutagenic drugs seem to be especially effective against persistent infections, with major evidences of lethal mutagenesis obtained during treatment of chronically infected hosts, i.e., HCV-infected patients treated with ribavirin, and mice persistently infected with norovirus and treated with favipiravir (25, 50).…”

Human Osteoblast-like Cells Are Permissive for Zika Virus Replication

“…ZIKV also targets neuronal cell types 7,8 and cells of the reproductive tract, including spermatogonia, Sertoli and Leydig cells, and vaginal epithelium 2,9 . This extensive tropism is paralleled by the detection of ZIKV in multiple body fluids, including tears, saliva, semen, cervical mucus, and urine 2,10 .…”

A Combination of Two Human Monoclonal Antibodies Prevents Zika Virus Escape Mutations in Non-human Primates

“…ZIKV causes mild symptoms consisting of fever, headache, rash, conjunctivitis, and arthralgia in an estimated 20% of infected individuals. In addition, infection is occasionally associated with severe neurologic problems that require hospitalization, such as meningoencephalitis or the immune-mediated Guillain-Barré syndrome (Miner and Diamond, 2017; Muñoz et al, 2016). The most severe consequences of infection are manifest in fetuses, which can develop devastating developmental aberrations, including microcephaly, collectively referred to as congenital Zika syndrome (Brasil et al, 2016; Del Campo et al, 2017).…”