Life Cycle of Zika Virus

MIC-4206 CE1(T2) Class Presentation

Name:-Rohit S. Mali
Roll No.:-353
History of Zika virus
• 1947: Scientists conducting routine surveillance for yellow fever in the Zika
forest of Uganda isolate the Zika virus in samples taken from a captive,
sentinel rhesus monkey.
• 1948: The virus is recovered from the mosquito Aedes africanus, caught on
a tree platform in the Zika forest.
• 1952: The first human cases are detected in Uganda and the United
Republic of Tanzania.
• 2015: Brazil notifies WHO of reports of an illness characterized by skin
rash in northeastern states. Zika was not suspected at this stage, and no tests
for Zika were carried out.
• February 2016: WHO declares that the recent association of Zika infection
with clusters of microcephaly and other neurological disorders constitutes a
Public Health Emergency of International Concern.
Structure of Zika Virus
• Zika virus is mosquito borne Flavivirus comprised
of an envelope and a nucleocapsid.
• The virus particles are spherical and small in size
(approximately 50 nm in diameter) with an electron-
dense core approximately 30 nm in diameter.  
• The virion surface contains envelope protein (E)
dimers and membrane (M) proteins in icosahedral-
like symmetry.
• Genome is ss (+) RNA (~11kb long) which encodes Fig. Structure of Zika Virus
for a polyprotein which is cleaved to form structural Image source:-https://www.virology.ws/zika/
and non structural proteins.
Fig. Structure of Zika virus genome
Image source:- Baz M, Boivin G. Antiviral
Agents in Development for Zika Virus
Infections. Pharmaceuticals (Basel). 2019 Jun
29;12(3):101. doi: 10.3390/ph12030101. PMID:
31261947; PMCID: PMC6789597.
Life Cycle of Zika virus
• Life cycle of Zika virus consists of 4 steps:-
1. Attachment and entry into host cell
2. Translation of viral RNA
3. Replication of viral genome
4. Assembly and release from cells.
1. Attachment and entry into host cell:-
i. E proteins are involved in the attachment of the virus to receptors on
the host membrane.
ii. The virus gets internalised via Clathrin-mediated endocytosis.
iii.  Viral RNA is released into the cytoplasm following fusion of the
viral and host membranes.
2. Translation of viral RNA:-
iv. The ORF of the Zika virus encodes for a polyprotein which is
processed by host and viral proteases in three structural proteins, the
C protein of nucleocapsid, prM a glycoprotein precursor of
membrane protein, and a glycosylated envelope protein E, along
with seven nonstructural proteins (NS) viz. NS1, NS2A/B, NS3,
NS4A, NS4B, and NS5, which are arranged from terminal N to C.
v. Viral RNA is translated using host translation machinery.
 Fig. ZIKV processes of attachment and entry

Image source:-
https://doi.org/10.1016/j.meegid.2019.01
.018
.
3. Replication of viral RNA:-
• Many of non structural viral proteins are associated with cellular
proteins during replication
• Cyclization of RNA is required for replication.
• NS1 participates in the replication complex together with the
transmembrane proteins (NS2A, NS4A and NS4B) and with the
cytoplasmic proteins NS3 helicase, NS2B co-factor and NS5.
• NS3 helicase is responsible for the unwinding of structured template
regions of RNA, working in a coordinated way with NS5 polymerase
during the de novo viral RNA synthesis.
• NS5 RdRp domains carry out the de novo RNA synthesis of one
negative polar-sense RNA from a positive template.
 Fig. Replication of Zika viral RNA
Image source:- Villordo SM, Gamarnik AV.
Genome cyclization as strategy for flavivirus
RNA replication. Virus Res. 2009;139(2):230-
239. doi:10.1016/j.virusres.2008.07.016
4. Assembly of virions:-
• Virus assembly occurs at the endoplasmic reticulum.
• The virion buds at the endoplasmic reticulum and is transported to the
Golgi apparatus.
• The prM protein is cleaved in the Golgi, thereby maturing the virion
which is fusion competent.
• Release of new virions by exocytosis.
Fig. Life cycle of Zika virus

Image source:-Gupta, Amit &

Kaur, Karambir & Rajput,
Akanksha & Dhanda, Sandeep
& Sehgal, Manika & Khan,
Shoaib & Monga, Isha &
Ahmad, Showkat & Singh,
Sandeep & Nagpal, Gandharva
& Usmani, Salman & Thakur,
Anamika & Kaur, Gazaldeep &
Sharma, Shivangi & Bhardwaj,
Aman & Qureshi, Abid &
Raghava, Gajendra & Kumar,
Manoj. (2016). srep32713-s1.
References
• https://www.who.int/news-room/feature-stories/detail/the-history-of-zika-virus
• https
://www.viprbrc.org/brc/staticContent.spg?decorator=flavi_zika&type=About&subtype=ZIK
V

• https://www.askscientific.com/zika-virus-life-cycle-pathogenicity-humans/
• Almerinda Agrelli, Ronald Rodrigues de Moura, Sergio Crovella, Lucas André Cavalcanti
Brandão,ZIKA virus entry mechanisms in human cells,Infection, Genetics and
Evolution,Volume 69,2019,Pages 22-29,ISSN 1567-1348,
https://doi.org/10.1016/j.meegid.2019.01.018.
• https://viralzone.expasy.org/6756
• James H. Strauss and Ellen G. Strauss, Viruses and Human Diseases,2 nd Edition(2008),
Academic Press
• Valente AP, Moraes AH. Zika virus proteins at an atomic scale: how does structural biology
help us to understand and develop vaccines and drugs against Zika virus infection?. J Venom
Anim Toxins Incl Trop Dis. 2019;25:e20190013. Published 2019 Aug 29. doi:10.1590/1678-
9199-JVATITD-2019-0013
Thank You