This presentation contains a brief discussion on the Zika virus infection in human brain and placenta with its worldwide prevalence. It also sheds light on the drugs that might be useful for inhibiting the virus and future research areas.

1. ZIKA VIRUS IN HUMAN
PLACENTA, DEVELOPING
BRAIN AND ITS
INHIBITION BY DRUGS
Sinjini Sarkar
M.Pharm (Pharmacology)
NSHM College of Pharmaceutical Technology
Presented at NATCONPH 2017
17.03.2017

2. What is Zika Virus?
ZIKA virus envelope structure
A. aegypti mosquito, vector of ZIKV
•A flavivirus, thought to be principally
transmitted to humans by Aedes
aegypti mosquitoes.
• First isolated in April 1947 in
Uganda from a monkey
• Parts of ZIKV resemble
neurovirulent West Nile and
Japanese encephalitis viruses, while
others similar to Dengue virus.
• Zika fever
• Can cause microcephaly in infants
and Guillain-Barré syndrome in
adults.

3. ZIKV in placenta and human
brain
Fig: Vertical Zika virus transmissionFig: ZIKV causes microcephaly

4. Case I : New born male was born at
9 months of gestation(C-section
delivery)
Died within 20 hrs
It was reported that the mother
had a viral infection (not
laboratory tested ) in the 3rd
month of pregnancy
3rd month USG revealed fetal
microcephaly and
malformations of limbs and
genitalia
The mother is from North
eastern Brazil and this was her
first pregnancy and denied use
of any medication during
Results:
•H & E stained slides of brain, liver,
spleen, heart , kidney showed
remarkable anatomopathological
injuries
• IHC analysis revealed diffusely
distributed immunopositivity in glial
cells and not in the heart. Liver,
spleen and kidney tissue samples.
•Real-time RT-PCR assays yielded
positive results for ZIKV RNA in
brain tissue samples and
negative results for DENV RNA.
Case Reports

5. Case II: 31-yr old woman living in
Northeast region of Brazil confirmed
her first pregnancy in May 2015
May 8th: First USG performed
indicating a fetal size compatible with
six weeks of development and normal
heart beat.
May 15th: She is presented with fever
and rash limited to 2 days. The
symptoms led to a clinical
epidemiological diagnosis compatible
with ZIKV disease.
June 22nd: (12th week of pregnancy)
Second USG performed and
examination failed to detect
embryonic heartbeat. The embryo
size was compatible with 8weeks of
development.
Curettage was performed.
Results: The placenta tissue samples
included decidua, amnion and
placenta; showed chronic placentitis
with chronic villous inflammation.
Immunohistochemistry analysis with
anti-flavivirus monoclonal antibody
showed immunopositivity in
Hofbauer cells and some
histiocytes but not in
trophoblastic epithelium.
RNA was extracted and with viral real-
time RT-PCR, it was found to be ZIKV
positive and DENV negative.

6. RESEARCH HIGHLIGHTS
• Quicke et.al, 2016; showed that primary
Hofbauer cells isolated from full-term placenta are
permissive to productive ZIKV infection and
initiates antiviral response in the body.
•Ghoussi et. al, 2016, concluded that ZIKA virus
elicits P53 activation and genotoxic stress in
human neural progenitors similar to mutations
involved in severe forms of genetic microcephaly
in a mouse model
• Retallack et.al cultured astrocytes in vitro from
human pluripotent stem cells and blocked AXL
surface receptor by an antibody. The results
showed decreased ZIKV entry.

7. Drug Inhibition Of ZIKV
Azithromycin
Sofosbuvir
Small molecule inhibitors

8. Discussio
n
Fig: Locally-acquired cases or virus isolation and serosurvey data

10. • The mechanism of placental transmission of ZIKV and
microcephaly is still unclear.
•ZIKV infection had been neglected till the massive
outbreaks in French Polynesia (2013-2014) and Americas
(2015-2016).
• February 2016: WHO declared ZIKV infection as a Public
Health Emergency of International Concern.
• June 2016: FDA granted the first approval for a human
clinical trial for a Zika vaccine.
• November 2016: WHO declared that Zika virus is no
longer a global emergency while noting that the virus
represents ‘ a highly significant and long-term problem’.

11. References:-
• Mem Inst Oswaldo Cruz, Rio de Janeiro, Vol. 111(5): 287-293, May 2016
• Cauchemez, S. et al. Association between Zika virus and microcephaly
in French Polynesia, 2013–15: a retrospective study. Lancet
http://dx.doi.org/10.1016/S0140-6736(16)00651-6 (2016)
•Quicke et al., 2016, Cell Host & Microbe 20, 83–90
July 13, 2016 ª 2016 Elsevier Inc.
•Cell Death and Disease (2016) 7, e2440; doi:10.1038/cddis.2016.266
• Retallack et.al; Zika Virus in the Human Placenta and Developing
Brain: Cell Tropism and Drug Inhibition;
http://dx.doi.org/10.1101/058883 doi: bioRxiv preprint first posted online
Jun. 15, 2016;

12. Acknowledgement
I would like to thank Prof. Dr. Subhasis Maity for
giving us a platform like NATCONPH 2017 to
express and groom ourselves.
I want to thank my mentor, Dr. Sandipan Dasgupta
for constantly providing insights and expertise that
greatly assisted me to carry on my work.
Lastly, I would also like to thank my classmates,
Dipika Banerjee, Abhirup Mukherjee and Priyanka
Ghosh, for supporting and encouraging me.