New research, published recently in Scientific Reports, has demonstrated that infection with Zika virus interferes with a wide array of cellular interactions, including genes responsible for cell division and neural differentiation. The findings have presented many cellular targets which could lead to opportunities for drug design.
The association between microcephaly and Zika has been reported previously; however, little is known about the cellular mechanisms that lead to microcephaly and other neural complications of Zika infection. Author Stevens Rehen, from the D’ Or Institute for Research and Education (Brazil), explained: “Elucidating the foundations of Zika virus infection is crucial in order to develop tools against it.”
Previous studies by this group have reported that, compared with non-infected cells, Zika infection caused a rapid depletion in pools of human neural stem cells. Building on these findings, the researchers were interested in investigating how Zika disrupts the interactome map of infected cells.
The team utilized human neural cells infected by strain of Zika virus obtained from a Brazilian patient. The cells were grown as 3D aggregates, termed neurospheres, which resemble fetal brain tissue therefore modeling early processes in brain development. The group then analyzed the expression levels of numerous genes and proteins in order to identify the molecular fingerprint of infected and non-infected cells.
Their analysis revealed that, compared with non-infectected neurospheres, over 500 proteins had altered expression levels in infected spheres. The researchers identified the roles of some of these proteins and discovered that many had functions such as repairing DNA damage or assuring chromosomal stability.
In addition, the team observed that proteins normally required for cell growth and specialization were silenced in infected cells, which may explain why infected the Zika infected cells died more quickly. In contrast, it was demonstrated that proteins associated with viral replication were upregulated by Zika infection.
This study uncovers some hypotheses towards the mechanisms behind symptoms such as microcephaly. Moreover, it may also preset targets for future drug development.
First author Patricia Garcez, from the Federal University of Rio de Janeiro (Brazil), concluded: “These findings provide insights into the molecular mechanisms of ZIKV infection over the course of brain development and may explain some of the consequences seen in the brain of newborns with microcephaly.”
Source: Garcez PP, Nascimento JM, Mota de Casconcelos J et al. Zika virus disrupts molecular fingerprinting of human neurospheres. Sci. Rep. doi:10.1038/srep40780 (2017) (Epub ahead of print); www.eurekalert.org/pub_releases/2017-01/difr-tio011917.php
Listen to our recent NCTalks podcast with first author Patricia Garcez here.