Brief pathophysiology concerning the zika virus.

1. Zika virus
PATHOGENESIS

2. Points to be focused on
▪ What does pathogenicity mean ?
▪ Recent zika developments
▪ Symptoms
▪ Research
▪ Speculation

3. Pathogenicity (definition)
▪ Pathogenicity - the quality of producing or the ability to produce
pathologic changes or disease.
▪ It also encompasses the mechanism with which the being causes
the disease.

4. Recent zika developments
▪ Purdue University researchers:
Michael Rossmann , Purdue
University’s Hanley
Distinguished Professor of
Biological Sciences, and
Richard Kuhn, director of the
Purdue Institute for
Inflammation, Immunology
and Infectious Diseases, stand
with the cryo-electron
microscope used to determine
the structure of the Zika virus.

5. Dendritic cells are antigen-presenting cells (also known
as accessory cells) of the mammalian immune system.
Their main function is to process antigen material and
present it on the cell surface to the T cells of the immune
system. They act as messengers between the innate and the
adaptive immune systems.

6. Cont…..
▪ The team found that all of the known flavivirus structures differ in
the amino acids that surround a glycosylation site in the virus
shell. The shell is made up of 180 copies of two different proteins.
These, like all proteins, are long chains of amino acids folded into
particular structures to create a protein molecule, Rossmann said.
▪ The glycosylation site where Zika virus differs from other
flaviviruses protrudes from the surface of the virus. A carbohydrate
molecule consisting of various sugars is attached to the viral
protein surface at this site.
▪ In many other viruses it has been shown that as the virus projects
a glycosylation site outward, an attachment receptor molecule on
the surface of a human cell recognizes the sugars and binds to
them, Kuhn said.

7. Cont…..
▪ The virus is like a menacing stranger luring an unsuspecting victim
with the offer of sweet candy. The human cell gladly reaches out
for the treat and then is caught by the virus, which, once attached,
may initiate infection of that cell.
▪ The glycosylation site and surrounding residues on Zika virus may
also be involved in attachment to human cells, and the differences
in the amino acids between different flaviviruses could signify
differences in the kinds of molecules to which the virus can attach
and the different human cells it can infect, Rossmann said.
▪ Glycosylation is an enzymatic process that attaches Glycans to
proteins, lipids or other molecules.

8. Cont…..
▪ Zika virus replicates in the mosquito's midgut epithelial cells and
then its salivary gland cells. After 5–10 days, ZIKV can be found in
the mosquito’s saliva which can then infect human.
▪ If the mosquito’s saliva is inoculated into human skin, the virus
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 virus
antigens have been found in infected cell nuclei.

9. SYMPTOMS
▪ Usually not manifested (80%)
▪ Observable 2-7 days after infection
▪ Extremely variable
▪ Usually self resolving (days to weeks)
▪ Include fever, conjunctivitis, joint and back pain, exanthema,
encephalitis, diarrhea, abdominal pain, dizziness, and anorexia.

11. Research: Human Trials
▪ “TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL
MEDICINE AND HYGIENE”
Vol. 58. No. 4. July, 1964.
COMMUNICATIONS: ZIKA VIRUS INFECTION IN MAN BY
D. I. H. SIMPSON*
(From the East African Virus Research Institute, Entebbe, Uganda)

12. Cont…..
▪ The patient (D.I.H.S.) :
 was a 28-year-old European male
 had been resident in Uganda for 2½ months
 had received 0.5 ml. of 17D yellow fever vaccine four
months before arriving in Uganda subcutaneously;
 had also received two (1 ml.) intramuscular doses of
louping-ill formol vaccine a further 2 months previously.

13. Cont…..
▪ Day 1
 The illness began with a slight frontal headache in the evening.
▪ Day 2
 There was a diffuse pink maculopapular rash which covered the face, neck, trunk
and upper arms.
 No itching, slight ache in back and thighs.
 Oral temperature was normal.
 The rash persisted and spread gradually to involve all four limbs including the
palms of the hands and the soles of the feet.
 By midday the patient was febrile and his temperature was found to be 99.4°F.

14. Cont…..
 The febrile stage was accompanied by slight malaise with pain in the back
and with frontal headache.
 In the evening, the temperature had returned to normal and the patient felt
much better, apart from slight headache. The rash still persisted but was
fading on the back and neck.
 Day 3
 No ill effects, temperature was normal, but the rash persisted on the trunk
and limbs. It faded slowly throughout Days 3 and 4.
 Day 5
 The rash disappears completely. No other signs or symptoms were noted
throughout the illness.

15. Research: Histopathology in Mice
▪ TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE
AND HYGIENE.
Vol. 46. No. 5. September, 1952.
ZIKA VIRUS PATHOGENICITY AND PHYSICAL PROPERTIES BY
G.W. A. DICK
National Institute for Medical Research, London. (From the Virus
Research Institute, Entebbe, Uganda.)

16. Cont….
▪ The pathological changes in mice sacrificed on the 1st day of signs of
infection have been confined to the central nervous system.
▪ Infiltration and degeneration including widespread softening have been
observed in the brains of some mice ; neuronal degeneration and cellular
infiltration have also been found in the cords.
▪ Intranuclear inclusions have been more obvious in pathological material
from baby mice than in adult mouse brains.
▪ No inclusion bodies were seen in the brains of mice which have been
sick for several days.
▪ In chronically ill animals there has been very extensive round cell
infiltration of the brain, and in some of them degenerative changes in
the viscera have been seen.

17. Speculation
▪ Even though at the current time the notion that “Zika causes
microcephaly” is running rampant in the media, Zika is yet to be
associated with microcephaly. Here are some points negating that
notion:
 Brazil has 3 million births a year; the notion that only 147
babies exhibit microcephaly seems statistically flawed.
 It is estimated that 500,000 – 1.5 mill. are currently
infected in Brazil
 FAS

18. References
▪ http://www.purdue.edu/newsroom/releases/2016/Q1/researche
rs-reveal-zika-virus-structure,-a-critical-advance-in-the-development-
of-treatments.html
▪ http://www.ncbi.nlm.nih.gov
▪ https://flavivirus.wordpress.com
▪ http://virologyj.biomedcentral.com/articles/10.1186/1743-422X-
7-24
▪ http://www.cdc.gov

19. Any questions?