سمنر حول فايروس الزيكا

1. ZIKAVIRUS
PhD student
Ghazwan Faisal Hussein

2. Structure of ZikaVirus
■ The virion is approximately 40 nm in diameter with surface projections that
measure roughly 5-10 nm.
■ Nucleocapsid is 25-30 nm in diameter surrounded by a host-membrane
derived lipid bilayer.
■ Enveloped.
■ Icosahedral.
■ Contains envelope proteins E and M.

3. Cont.….
■ Group IV ((+)ssRNA) Non-
segmented, single-stranded,
positive-sense RNA genome.
■ Family: Flaviviridae
■ Genus: Flavivirus
■ Species: Zika virus
■ Reserviour : Aedes mosquitoes -
such as A. aegypti

5. Genome of ZikaVirus
 Zika virus is an icosahedral ,enveloped , a positive single stranded RNA virus
with non-segmented genome and size of genome about 11 kb nucleotides long
the Zika virus genome contains 10,794 bp nucleotide long encoding 3,419
amino acids .This single transcript gives a polypeptide which processed into 3
structural proteins:
1-(capsid) [C]
2-premembrane /membrane [prM]
3-envelope [E]
4- seven nonstructural proteins : (NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5)
The NS1, NS3 and NS5 proteins are large and highly conserved, meanwhile the
NS2A, NS2B, NS4A and NS4B proteins are small and hydrophobic.

7. Virulence factors
Virus particle contains a lipid bilayer, one genome RNA, and three distinct types of
viral proteins:
■ 1. E - envelope protein : The envelope (E) glycoprotein, embedded in the
membrane, allows attachment of the virus particle to the host cell receptor to
initiate infection, also Zika virus envelope proteins have been shown to play a
major role in virus assembly.
2. M - membrane protein/prM – premembrane protein : play a crucial role in the
biogenesis of the envelope of Zika virus and Acts as a chaperone for envelope
protein E during intracellular virion assembly by masking and inactivating
envelope protein E fusion peptide. prM is the only viral peptide matured by host
furin in the trans-Golgi network.
■ 3. C - capsid or core protein (Protein C): Plays a role in virus budding by binding
to membrane and gathering the viral RNA into a nucleocapsid that forms the
core of a mature virus particle.

9. virulence factors….cont
■ 4- Peptide pr: Prevents premature fusion activity of envelope proteins in trans
Golgi by binding to envelope protein E.
5- Non-structural protein 1: Involved in immune evasion, pathogenesis and viral
replication. Once cleaved off the polyprotein, is targeted to three destinations:
the viral replication cycle, the plasma membrane and the extracellular
compartment. May plays a role in viral genome replication. Assist membrane
bending and envelopment of genomic RNA at the endoplasmic reticulum.
Excreted as a hexameric lipoparticle that plays a role against host immune
responce.
6- Non-structural protein 2A: Component of the viral RNA replication complex
that functions in virion assembly and antagonizes the host immune response.
7-Non-structural protein 2B: Required cofactor for the serine protease function
of NS3.

11. Epidemiology
 The zika virus was first isolated in April 1947 from a rhesus macaque monkey
that had been placed in a cage in the Zika Forest of Uganda, near Lake Victoria,
by the scientists of the Yellow Fever Research Institute.
 A second isolation from the mosquito. Africans followed at the same site in
January 1948. When the monkey developed a fever, researchers isolated from
its serum a transmissible agent that was first described as Zika virus in 1950.
In humans, the virus causes a mild illness known as Zika fever, Zika, or Zika
disease, which since the 1950s has been known to occur within a narrow
equatorial belt from Africa to Asia. In 2014, the virus spread eastward across the
Pacific Ocean to French Polynesia, then to Easter Island and in 2015 to Mexico,
Central America, the Caribbean, and South America, where the Zika outbreak
has reached pandemic levels.

12. Pathogenicity
 Also there is growing evidence that links Zika to microcephaly, a neurological
disorder in which babies are born with smaller than normal heads and brains,
according to researchers in Brazil and the Pan American Health Organization
(PAHO), the regional arm of the WHO.
 And the virus has also been associated with cases of Guillain-Barré syndrome,
a poorly understood condition in which the immune system attacks the nervous
system, sometimes resulting in paralysis. “A causal relationship between Zika
virus infection and birth defects and neurological syndromes has not been
established but is strongly suspected.

14. Mode of transmission
 Zika virus (ZIKV) is transmitted to people through the bite of an infected
mosquito from the Aedes genus, mainly Aedes aegypti in tropical regions. This
is the same mosquito that transmits dengue, chikungunya and yellow fever.
Zika is mainly transmitted by the mosquito species Aedes aegypti or Aedes
albopictus. It may also be transmitted by blood transfusion or unprotected sex.
Once the Zika virus get into the bloodstream of a pregnant woman, the virus
may cross the placenta and infect the foetus’s neural progenitor cells (NPC),
which form the brain’s outer layer. Damaged NPC creates fewer neurons,
leading to decreased brain volume.

16. Signs and symptoms of Zika virus infection
1.The most common symptoms of Zika are fever, rash, joint pain, or conjunctivitis
(red eyes). Other common symptoms include muscle pain and headache. The
incubation period (the time from exposure to symptoms) for Zika virus disease is not
known, but is likely to be a few days to a week.
2.The illness is usually mild with symptoms lasting for several days to a week.
3.People usually don’t get sick enough to go to the hospital, and they very rarely die
of Zika.
4.Zika virus usually remains in the blood of an infected person for about a week but
it can be found longer in some people.

18. CYTOPLASMIC REPLICATION
 Zika virus replicates in the mosquito's midgut epithelial cells and then its salivary
gland cells. After 5–10 days, the virus can be found in the mosquito’s saliva. If
the mosquito’s saliva is inoculated into human skin, the virus can infect
epidermal keratinocytes, skin fibroblasts in the skin and the Langerhans cells.
The pathogenesis of the virus is hypothesized to continue with a spread to
lymph nodes and the bloodstream. Flaviviruses generally replicate in the
cytoplasm, but Zika antigens have been found in infected cell nuclei.

20. Diagnosis for ZIKV infection include :
 1-PCR tests to detect viral DNA , PCR tests should be conducted within 10 days of
onset of illness.
2-Detection by ZIKV antibody (IgM) in serum , IgM for ZIKV is typically detectable
around 3-5 days after infection, but cross-reactivity with closely related dengue,
yellow fever, Japanese encephalitis, and West Nile viruses are possible.
3-Several methods can be used for diagnosis, such as viral nucleic acid detection,
virus isolation and serological testing.

21. Treatment
 Similar to other arboviral diseases, there is no specific antiviral drug treatment
for ZIKV infection. Symptomatic treatment is recommended after excluding more
serious conditions like malaria, dengue, and bacterial infections. In acute
infection, treatment is symptomatic and supportive, consisting of rest and the
use of acetaminophen to relieve fever or use of ibuprofen, naproxen, or another
non-steroidal anti-inflammatory agents (NSAID) to relieve the arthritic
component.
 Up to March, 2016 there is no available vaccine against the Zika virus. There
are several proposals for a vaccine, using the same methodology as other anti-
flaviviruses vaccines70; nevertheless, the process is still long. There are ethical
issues involving pregnant women and the “safe use” of vaccines, which are still
a barrier.