Though
microcephaly is known to be caused by this virus, the cellular changes that
lead to the development of this condition has so far been unknown. The
principal investigator and researcher of the study
said
that detailing the foundations of Zika virus is a crucial step in developing
therapy against the infection.
‘Molecular interactions of Zika virus in growing neural cells provide targets for drug therapy.’
Depletion of Human Neural Stem Cells:
In
an earlier study conducted by Dr. Stevens and colleagues, it was found that the
Brazilian strain of the Zika virus that infected human neural cells, lead to
the
complete depletion of the human neural stem cells when compared with
cells that were not infected. This study formed the foundation for the current
study as it identified the effect of the Zika viral infection on brain cells
although the pathway that lead to the depletion was not identified.
Interactome of Zika Infected Cells:
The
research team began to determine the cellular and molecular interactions of the
Zika virus in the given cellular network, called the
interactome map.
Investigating the interactome map would reveal
- the cellular targets of the virus
- the pathway of the infection
- the cellular mechanisms modulated by the virus
An
understanding of these factors will aid in identifying potential targets for
drug therapy against the virus and could aid in designing better treatment. The
microcephaly caused among newborns has been a great cause of concern and an understanding of the mechanisms that contribute to the
development of this condition would provide insights into possible mechanisms
of prevention.
Molecular Fingerprinting:
Zika
virus strain from Brazil was found to be more virulent than other strains of
the Zika virus. Therefore in this study, Zika virus strain from a Brazilian
patient was
isolated and used to infect human neural cells. The infected
cells were then organized into
3D aggregates, called
neurospheres,
which resembled the fetal brain tissue that was normally found during the early
stages of brain development. The next
step in the research involved understanding the molecular fingerprinting of
cells infected with the virus as well as normal uninfected cells by identifying
the expression patterns as well as the status of various genes and proteins.
The
study found that
- There was an alteration of the expression levels (either down-regulation or
up-regulation) of more than 500 proteins in the infected neurospheres when
compared with neurospheres of cells that were not infected.
- Some of the proteins that were altered included those
that were associated with fixing damage to DNA or those that were involved
in maintaining chromosome stability.
- Certain proteins that were required for the normal
cellular growth became silent or did not exert their function in cells
that were infected with the Zika virus. This could be the reason behind
the early death of cells that were infected with the Zika virus when
compared to normal cells.
- The genes that were associated with specialization of
cells were also found to become silent among the infected neurospheres.
This process occurred before the development of the specialized brain
cells which could be one of the factors that contribute to the
neurological symptoms associated with this infection.
- The proteins that were required for the multiplication
and development of the virus were found to be present in abundance; this
is probably a mechanism of invasion that is adopted by the virus to
increase its numbers.
The
study that is titled "
Zika virus disrupts molecular fingerprinting of
human neurospheres" and published in the Journal
Scientific Reports consists of a complete list of all human
proteins which were found to be altered in neurospheres that were infected by
the Zika virus.
The
first author of the study who is an assistant professor at the Federal
University of Rio de Janeiro
Dr.Patricia Garcez when asked about the
significance of the study findings said that they provided an insight into the
molecular mechanisms that were involved in Zika infection that occurred during
brain development and provide a clue to some of the consequences that are
witnessed in the brain of newborns who are affected by microcephaly.
Zika
virus infection was considered a '
public health emergency' by the WHO in
2016 as the number of infected cases began to increase. The most alarming
symptom associated with this condition was the development of microcephaly
among newborns. This created a stir among pregnant women, with increased alarm,
especially in Brazil. The current study highlights the pathways and the
proteins that were involved in brain cell infection, providing insights into
possible drug targets.
References :- Zika virus - (http://www.who.int/mediacentre/factsheets/zika/en/)
Source: Medindia
