- Zika virus infection is a mosquito borne illness that can harm the
fetus and currently there are no drugs or vaccines approved for use in
pregnancy to protect the fetus from getting infected.
- Current study shows that hydroxychloroquine, an antimalarial drug
could help prevent Zika virus transmission to fetus.
of Zika virus infection to fetus can be prevented by administration of
hydroxychloroquine during pregnancy, according to a study at Washington
University School of Medicine in St. Louis. The findings appear on the 10th
July publication of The Journal of Experimental Medicine
Need for Zika Virus Treatment in Pregnancy
‘Hydroxychloroquine, if approved for use in pregnancy to prevent fetal Zika virus infection, would be a major breakthrough in reducing dreaded neurological complications in the fetus.’
As mentioned, Zika virus infection
is associated with severe neurological complications in
the fetus such as microcephaly (abnormally small heads)
signifying reduced brain development. Currently, there are no approved drugs or
vaccines for use during pregnancy, and infections during pregnancy pose a
serious threat to both the mother and the fetus.
More recently, in 2015, doctors in Brazil
noticed the birth of several babies with microcephaly indicating the possible spread
of the virus in tropical America. Helpless as they were with no drugs or vaccines to treat the feared
infection, all they could suggest were mosquito preventive measures
wearing protective clothing or using repellent creams or sprays.
The current research team focused their
attention on the placenta, which is the
last barrier to protect the fetus from infection
so to say, when other
mechanisms fail to eliminate the virus and look for concrete solutions to
protect both the mother and the fetus.
Role of the Placenta - How it Works
The mechanism by which placenta performs
its immune function is through
activation of autophagy or cellular scavenging or clearing pathways
ultimately destroy and get rid of unwanted cellular proteins and debris as well
as foreign agents such as microbes.
However, the Zika virus was found to be
able to invade the placenta and also multiply within the placental cells,
breaching all defence mechanisms.
The study team wished to explore how the
Zika virus managed to do this and proceeded with their research to get answers.
Barrier Versus Zika Virus - How the Virus Gains the Upper Hand
The following are the key observations
made by the study team when they experimentally induced Zika virus infection in
the placenta and noted their findings.
- Following Zika virus infection of
the human placental cells, the genes promoting autophagy were activated or turned on.
- When drugs that promoted autophagy
were added, the viral count in the placental cells surprisingly went up.
- On the contrary, when drugs that
suppressed autophagy were added, the viral count in the placenta went
These surprising findings led to the
conclusion that upping the
autophagocytic process actually helped viral multiplication while suppressing
autophagy reduced the viral proliferation
. In other words, the virus had
found a way to breach the well-established cellular defence mechanism and use
it to its advantage.
The team validated the above findings in two groups of pregnant mice, one with
normal autophagy response and the others with suppressed autophagy response
, after infecting them
with the Zika virus.
- Five days after infection, both groups had the
same amount of virus in their bloodstreams. However, the mice with suppressed autophagy had 10 times less virus in their
placenta compared to their normal counterparts.
- There was less
placental damage and less neurological damage to the fetus in mice with
suppressed autophagy response.
"It appears that Zika virus takes
advantage of the autophagy process in the placenta to promote its survival and
infection of placental cells," said Bin Cao, PhD, and a postdoctoral
fellow at the University.
Hydroxychloroquine Drug In Pregnant Mice
The scientists then went on to test if administration of
hydroxychloroquine to pregnant mice
would reduce transmission of Zika virus
infection to fetal mice. This was because hydroxychloroquine
exerts some of its therapeutic effects (in other conditions) by suppressing
- Female mice with a normal autophagy
response were infected with Zika virus on day 9 of gestation.
- These mice were then divided into
two groups, one dosed with hydroxychloroquine and the other group with
placebo over the next five days.
treated with hydroxychloroquine showed significantly less virus in their
placentas and fetuses. Also the damage to the placenta and
fetus was significantly lower in comparison to mice not treated with
- The fetuses resumed normal growth
and development in treated mice.
- However, the virus count in the
bloodstream of both groups remained the same, indicating that hydroxychloroquine was able to protect
fetal and placental damage inspite of circulating virus in the mother.
"We found that the malaria drug hydroxychloroquine
effectively blocks viral transmission to the fetus," said senior author
Indira Mysorekar, PhD, an associate professor of obstetrics and gynecology, and
of pathology and immunology. "This drug already is used in pregnant women
to treat malaria, and we suggest that it warrants evaluation in primates and
women to diminish the risks of Zika infection and disease in developing
- Safety Factor of Hydroxychloroquine Needs to be Evaluated
In conclusion, the current study strongly
suggests that hydroxychloroquine protects against fetal Zika virus infection
when administered during pregnancy. This drug is already approved for use in
pregnancy for other conditions, notably malaria. However, since pregnant women may be required to take hydroxychloroquine for
extended periods during pregnancy for protection against the Zika virus,
further studies are needed to establish the safety of its longterm use in the
mother and the fetus
"We would urge caution but
nevertheless feel our study provides new avenues for feasible therapeutic
interventions," said Mysorekar, who is also co-director of the
university's Center for Reproductive Health Sciences. "Our study suggests
that an autophagy-based therapeutic intervention against Zika may be warranted
in pregnant women infected with Zika virus."
- Chloroquine and hydroxychloroquine for cancer therapy - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4905171/)