Zika Virus

In addition to eukaryotes and prokaryotes, tiny organisms called viruses are present in our
surrounding. Viruses rely on a host for survival; the host can be a bacterial cell, animal cell, plant
cell or human cell. The structure of a virus impacts it process of replication (function), which can
be more complex than predicted. The general structure of a virus includes: DNA or RNA genetic
material, capsid and an envelope.
Why are we concerned about viruses? These tiny organisms, smaller than the size of
bacteria are capable of infecting all types of life forms (1). Virus particles attack the cell and
take over its machinery to carry out their own life processes of multiplication and growth (2).
The entry of a virus into a cell involves its attachment on the cells surface with the help of cell
receptors. They follow a path called the lytic cycle to infect cells. Additionally, viruses are
spread in many ways. For example, viruses in animals can be carried by blood-sucking
insects(1). This way of transmission is extremely important, specifically to the understanding of
ZIKA virus.
In 1947, Zika virus was first isolated from a rhesus macaque monkey in the Zika Forest
located in Uganda. Specifically, this forest is located next to the swamps of Waiya Bay. This
virus comes from the Flavivridae family and Flavivrus genus. What is Flaviviridae? This
particular family of virus spreads through arthropod vectors and gets its name from the Yellow
Fever virus (3). The arthropod vectors for Zika virus are daytime-active Aedes mosquito, such
as A. aegypti and A. albopictus. (4). After isolating the virus, the first evidence of human
infection occurred in 1952. Upon researching, 50 out of the 84 people infected had already made
antibodies against the virus. Currently, there is a widespread outbreak of Zika virus in the
Americas (4).
Zika virus like the other Flaviviruses has an envelope that contains viral glycoproteins
and is responsible for protecting the icosahedral nucleocapsid. The envelope is covered in a
phospholipid bilayer; this bilayer is picked up from the host cell membrane. The glycoproteins
on the bilayer are extremely important because without these proteins, the virus cannot bind to
the host cell receptor and therefore is unable to penetrate and replicate inside the cell. The Zika
virus has two glycoproteins. Glycoprotein E is the interesting one because there is a notable
difference in the key surface protein when compared to other flaviviruses (5). The E gene codes
for the envelope protein which composes the majority of the viron surface and is involved with
aspects of replication such as host cell binding and membrane fusion (9). Apparently, the
variation in the E glycoprotein of Zika virus could explain the ability of the virus to attack nerve
cells, as well as the associations of Zika virus infection with birth defects and the neurological
Guillian-Barre syndrome (5). Moreover, glycoproteins may help the virus avoid the hosts
immune system. The nucleocapsid is equally important too. Viral nucleocapsid is basically a
protein coat made up of small subunits called capsomeres and nucleic acid, the nucleic acid,
which can be either DNA or RNA; in our case, it is RNA. The nucleocapsid of the virus is in the
shape of an icosahedral; this allows the capsomere subunits to assemble easily. Lastly, the
nucleic acid within the capsid for the Zika virus is positively single stranded RNA. Zika virus is
an RNA virus and it does not include DNA intermediates in its replication cycle; therefore, it
does not integrate into the hosts genome (1).
The genome of the Zika virus is composed of coding genes, 2 non-coding regions, and 1
non-coding RNA of the positive single stranded RNA. These genes are important because they
help with viral replication, translation, genome stabilization and more. The genome is linear and
consists of 10,794 base pairs (6). The single-stranded RNA molecule as previously mentioned

contains 2 non-coding regions known as the 5NCR and the 3NCR(6). The other part of the
genome structure is the ORF also known as the open reading frame, and this part is important
because it codes for the Zika virus polyprotein which is cleaved during post-translation by
cellular and viral enzymes (6). The ORF of the Zika virus is 5-C-prM-E-NS1-NS2A-NS2BNS3-NS4A-NS4B-NS5-3 and is cleaved into 3 structural and 7 nonstructural genes. The
structural genes are gene C, prM and E and non-structural genes are the NS genes. According to
the MircrobeWiki website, the NS1, NS3 and NS5 genes are large and highly conserved rather
than the NS2A, NS2B, NS4A, and NS4B (6). This makes sense because the NS3 gene is a
protease and it helps with protein catabolism and the NS5 gene is a polymerase, which is in
charge of synthesizing nucleic acids. The other NS genes are just smaller, hydrophobic proteins
(6). Moreover, the C gene codes for the capsid, prM gene codes for membrane precursor protein
and E gene codes for envelope. The genome of this virus is +ssRNA; therefore, the host cell
immediately translates it; the main reason behind this immediate translation is the similarity of
the viral RNA compared with mRNA (7).
Once inside of the cell, how does the Zika virus replicate? Before infecting humans, the
virus replicates inside the vector, the Aedes mosquitoes. The virus specifically replicates in the
nucleus of the mosquitos cell located in the midgut epithelial cells of the mosquito and then
moves to the salivary glands. When the mosquito bites, the proboscis of the mosquito goes
through both the epidermis and dermis layers of the skin (4). The main target of the mosquitoes
is the skin cell according to all the articles. The dermis layer of the skin contains blood that the
mosquito feeds on. (4) Interestingly, some of the skin cells: keratinocytes, fibroblasts, and
dendritic cells are permissive; they have receptors that allow the virus to enter the cell (4). So,
the first step of Zika virus replication involves attachment of the viral envelope protein E to host
receptors, which mediates internalization into the host cell by apoptotic mimicry(8). Next, the
Zika virus fuses with host membrane allowing the release of +ssRNA genome into the cytoplasm
(8). After that, the RNA is immediately translated into a polyprotein, which is later cleaved by
cellular and viral enzymes; this process yields replication proteins (8). The replication takes
place on the surface of the ER and dsRNA is synthesized from +ssRNA. The dsRNA is later
transcribed leading to viral mRNAs. Lastly, in order to exit the cell, the virus assembles and then
buds out of the ER and goes to the Golgi apparatus where the prM protein is cleaved causing the
virion to mature and exit via exocytosis (8).
The main target of Zika as said before seems to be skin cells. We can confirm this
because out of the different symptoms reported: mild fever, conjunctivitis and muscle pain. Out
of all these symptoms, skin rash is the most common (1). Additionally, it is important to note that
not every person infected shows symptoms. The incubation period generally last from few days
to a week. Research indicates that only 20% of people infected actually show symptoms (1). The
Zika virus is not very harmful in some situations; it is a relatively mild disease of limited scope
(4). People infected with this virus are advised to take plenty of rest, drink water to prevent
dehydration and maybe take acetaminophen to help with the pain (1). As I mentioned before, the
Zika virus is not harmful in some situation, not all situations. One bad situation to be associated
with the Zika virus is during pregnancy. The virus can lead to pregnancy problems (4).
Microcephaly is one major problem that we worry about because evidence has suggested that
Zika can infect neurons or neuron progenitors. This disease causes a decrease in the babys brain
growth, which leads to a small head (9). There are also other problems associated with
microcephaly, these include: intellectual disability, seizures, vision problems and more (9). In the
Epidemic of Zika Virus article, a reexamination of data was done which revealed cases of

microcephaly in women who were pregnant during the outbreak of the virus (9). Also, it
revealed increased cases if Guillain-Barre syndrome after the outbreaks of Zika in French
Polynesia and in Pernambuco (10). Additionally, Zika viruss RNA was present in the amniotic
fluid of 2 pregnant women whose fetuses had microcephaly (10). Moreover, the Zika Virus:
History, Emergence, Biology and Prospects for Control article determined that Zika virus can
infect human neural progenitors derived in virtro by inducing pluripotent stem cells (11). This
statement suggests that the virus could infect neuroblasts in vivo (11). There is also a strong
relation between the outbreak of Zika virus and an increase in the amount Guillain-Barre
syndrome (11). Guillain-Barre syndrome is a disorder, which causes ones immune system to
attack its own body; specifically attacking some parts of the peripheral nervous system. Main
evidences confirming the relationship between the virus and microcephaly include: women
pregnant during the outbreak had babies with microcephaly and the virus was present in the
amniotic fluid of 2 pregnant women (10). Additionally, Brazil has experienced a massive
outbreak of the virus and the officials there reported an increase in the number of cases of babies
born with microcephaly (12).

Works Cited
1. Virus. (n.d.). Retrieved April 10, 2016, from https://en.wikipedia.org/wiki/Virus
2. Mandal, A., Dr. (2010). What is a Virus? Retrieved April 10, 2016, from http://www.newsmedical.net/health/What-is-a-Virus.aspx
3. Flaviviridae. (n.d.). Retrieved April 10, 2016, from https://en.wikipedia.org/wiki/Flaviviridae
4. Zika virus. (n.d.). Retrieved April 10, 2016, from https://en.wikipedia.org/wiki/Zika_virus
5. Structure of Zika Virus Determined. (n.d.). Retrieved April 10, 2016, from
https://www.niaid.nih.gov/news/newsreleases/2016/Pages/Zika-structure.aspx
6. (n.d.). Retrieved from https://microbewiki.kenyon.edu/index.php/Zika_virus
7. RNA virus. (n.d.). Retrieved April 10, 2016, from https://en.wikipedia.org/wiki/RNA_virus
8. ViralZone: Zika virus (strain Mr 766). (n.d.). Retrieved April 10, 2016, from
http://viralzone.expasy.org/all_by_species/6756.html
9. Facts about Microcephaly. (2016). Retrieved April 10, 2016, from
http://www.cdc.gov/ncbddd/birthdefects/microcephaly.html

10.The Epidemic of Zika VirusRelated Microcephaly in Brazil: Detection, Control, Etiology, and Future
Scenarios.American journal of public health, 106(4), 601-605.

Hamel, R., Ligeois, F., Wichit, S., Pompon, J., Diop, F., Talignani, L., ... & Miss, D. (2016).

11. Zika Virus: History, Emergence, Biology, and Prospects for Control. Antiviral Research.

Teixeira, M. G., da Conceio N. Costa, M., de Oliveira, W. K., Nunes, M. L., & Rodrigues, L. C. (2016).

12. Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, 18 Mar.
Web. 25 Apr. 2016.

2016.