New drug targets for Zika found
WASHINGTON: Zika virus interferes with cell division and alters the expression of hundreds of genes guiding the formation and development of neurons, according to a new study published on Monday that may pave the way for new therapies to treat the infection.
Zika virus (ZIKV) infection is linked to microcephaly - a condition in which baby's head is abnormally small, often because the brain has not developed properly - and other fetal brain defects.
Despite the association, cellular alterations caused by the virus are largely unknown.
“Elucidate the underpinnings of ZIKV infection is very important to develop tools to combat it”, said Stevens Rehen, scientist at Institute of Biomedical Sciences at Federal University of Rio de Janeiro (UFRJ) in Brazil.
In a previous research, the scientists noticed that the pool of infected neural stem cells was completely depleted after one week. In the present study, they decided to explore how neural cells react to ZIKV infection before dying.
To do so, human neural cells were exposed to a strain of ZIKV collected from a Brazilian patient and coaxed to become neurospheres, organised aggregates of neural cells resembling fetal brain tissue.
By means of state-of-theart techniques, researchers evaluated the interactome map - a whole set of molecular interactions - of the infected neural cells in order to understand the ZIKVrelated impairment on cellular metabolism.
To identify the molecular fingerprints of the ZIKV infection, the authors investigated gene and protein expression in both infected and non-infected cells.
The analysis showed more than 500 genes per proteins altered in the infected developing brain cells.
A few of them associated with DNA damage and chromosomal instability, such as aneuploidy. Others, normally active during cellular division, were silenced in infected cells, thwarting their ability to multiply. In addition, genes driving cell specialisation were repressed in ZIKV infected cells.
“These findings provide insights into the molecular mechanisms of ZIKV infection and likely explain some of the consequences seen on brain formation and function at these crucial points of brain development,” said Patricia Garcez, assistant professor at UFRJ. The study was published in the journal Scientific Reports.