3. INTRODUCTION:
PICO - Small RNA viruses
• Picornaviruses represent a very large virus family
with respect to the number of members but one of
the smallest in terms of virion size and genetic
complexity
• Two major groups of human
• Enteroviruses
• Rhinoviruses
4. GENERAL PROPERTIES:
• Virion: Icosahedral, 28–30 nm in diameter, contains 60 subunits
• Composition: RNA (30%), protein (70%)
• Genome: Single-stranded RNA, linear, positive-sense, 7.2–8.4 kb in
size, MW 2.5 million, infectious, contains genome-linked protein (VPg)
• Proteins: Four major polypeptides cleaved from a large precursor
polyprotein. Surface capsid proteins VP1 and VP3 are major antibody-
binding sites. VP4 is an internal protein.
• Envelope: None
• Replication: Cytoplasm
5. Structure & Composition
Structure of a typical picornavirus. Exploded diagram showing internal location of the
RNA genome surrounded by capsid composed of pentamers of proteins
VP1, VP2, VP3, and VP4. Note the "canyon" depression surrounding the vertex of the
pentamer.
8. CLASSIFICATI
ON
Picarnoviridae family- 9 genera,
(6 genera medically important )
1. ENTEROVIRUS
2. RHINOVIRUS
3. HEPATOVIRUS (Hepatitis A)
4. PARAECHO VIRUS
5. APHTHO VIRUS (foot &mouth disease)
6. CARDIOVIRUS
9.
10. Picornavirus Replication
• Occurs in the cytoplasm of cells.
• First the virion attaches to a specific receptor in
the plasma membrane.
• Release of viral RNA in to the cell viral RNA
translation.
• RNA replication
• Maturation by formation of protomers which are
aggreagates Of VP0, VP1 and VP3
11. • these protomers assemble which package plus
standed RNA to from ”provirions”
• VP0 → VP4 &VP 2 → mature virus particles
release by cell disintegration.
• Multiplication cycle takes : 5 – 10 hours.
12. Entry of Poliovirus into Cells
Nonenveloped poliovirus enters
cells by forming a pore in the
membrane of the cell.
During interactions of poliovirus with
its receptor major conformational
rearrangements occur in the virus
particle.
The particles lose VP4 and the
hydrophobic N-terminus of VP1 is
displaced to the virion surface
N-termini of VP1 forms a pore in the
cell mebrane through which the
RNA is released into the cytosol.
Some evidence suggests that virus
particles may undergo endocytosis
in some cell types.
13.
14. ENTEROVIRUSES
• Relatively stable viruses surviving for long
period in water, sewage,organic matter etc.
• They resist pH of 3 for few Hrs.
• Calcium chloride density is 1.34gm/ml.
15. ENTEROVIRUS GROUP
1. Poliviruses types 1 – 3
2. Coxsackieviruses group A ( 1 – 24 no type 23)
3. Coxsackie viruses group B ( 1 – 6 )
4. ECHO viruses types 1 – 33 ( no 10 or 28)
5. Entro viruses types 68 – 71
17. POLIOVIRUSES
• Polioviruses are the cause of poliomyelitis, a
systemic viral infection that predominantly
affects the CNS, causing paralysis.
polios =“gray”
myelos =“marrow” or “spinal cord”
• Now commonly shortened to polio, is
descriptive of the pathologic lesions that
involve neurons in the gray matter, especially in
the anterior horns of the spinal cord.
18. HISTORY:
• Sporadic poliomyelitis cases were published as early
as 1840
• the first descriptions of the natural history and
neurologic complications of poliomyelitis were
recorded in Sweden by Karl Oskar Medin in 1890.
• In 1908, Landsteiner and Popper demonstrated that
polio was caused by a “filterable virus”
19. • In 1949, Enders, Weller, and Robbins proved that poliovirus
could be propagated in vitro in cultures of human embryonic
tissues of non-neural origin.
• This discovery facilitated experimental investigation of the
pathogenesis of the disease in primates and the development
of vaccines.
• Bodian and associates first recognized the three distinct
serotypes of poliovirus.
• Salk reported in 1953 that human subjects could be
successfully immunized with formalin-inactivated
poliovirus, a discovery that rapidly led to an extensive field
trial and licensure of IPV in 1955.
20. GENERAL PROPERTIES:
• Poliovirus particles are typical enteroviruses.
They are inactivated when heated at 55 °C for 30
min, but Mg2+,1 mol/L, prevents this inactivation.
• purified poliovirus is inactivated by a chlorine concentration
of 0.1 ppm, much higher concentrations of chlorine are
required to disinfect sewage containing virus in fecal
suspensions and in the presence of other organic matter.
• Polioviruses are not affected by ether or sodium
deoxycholate.
21. • Polio virus survives in sewage, water, fecal matter for
days to weeks.
• Survives in milk & ice creams for long period
• Resists stomach acidity
• Resists routinely used chlorination of water(0.1ppm)
22. Host range & cultivation:-
• Restricted host range .(natural infection: MAN)
• Monkeys – by inoculation into brain of spinal cord.
• Chimpanzees – Oral → Asymptomatic → intestinal Carriers
• Can be grown in Primary or continuous cell cultures derived from
human or monkey kidneys.
• Poliovirus requires a primate – specific membrane Receptor for
infection ,
• Liposomes & viral receptor gene introduction Converts resistant
cells to susceptible cells.
23. ANTIGENIC PROPERTIES :-
• 3antigenic types : 1,2,3
• prototype strain are :
1. Brunhilde & Mahoney :type 1 : Epidemics
2. Lansing & MEFI : type 2 : endemic
3. Leon & saukett : type 3 : epidemics.
• By ELISA & CFT – 2 antigens can recognised
• They are
• D [ dense]
• C [ coreless or capsid]
24. MODE OF INFECTION & PATHOGENESIS
• Source of infection is Infectied individual
Apperant infection
Inapparent infection
Convalescent carriers
25. Pathogenesis:-
Ingestion of contaminated water
Reaches & multiplies in intestinal epithelial cells
Further multiplication in peyer’s patches
Enters to regional lymphatics
Enters into blood stream (viraemia)
26. Seeded into CNS by blood
Virus multiplies selectively in neurons
Degeneration of Nissl’s bodies (chromatolysis)
Aseptic meningitis
In some cases progress to poliomyelitis
27.
28.
29. CLINICAL FINDINGS :-
• Inapparent infection to a mild febrile illness to severe
permanent paralysis.
• Incubation period : 7 – 14 days.
32. Abortive poliomyelitis :-
Most common form
Minor illness
(fever,malaise,headache,nausea,vomiting,constipation,sore throat)
Recovers in few days
Non paralytic poliomyelitis ( aseptic meningitis)
Stiffness & pain in the black & neck .
Lasts for 2 – 10 days, recovery rapid.
33. Paralytic poliomyelitis :-
• Flaccid paralysis from lower motor neuron damage.
• Incoordination due to brain stem invasion
• maximal recovery Within 6 months with residual paralysis lasting
longer.
Progressive post poliomyelitis muscle atrophy:-
• A recrudescence of paralysis & muscle wasting in patients
decades after their experience with paralytic poliomyelitis.
34.
35. LABORATORY DIAGNOSIS :-
A. Recovery of virus :-
• Throat swabs – soon after onset
• Rectal swab or stool – Longer periods
• CSF – virus not demonstrated/not recovered
• Specimens kept frozen during transit
• Human or monkey kindly cell cultures are
inoculated, incubated & observed.
• CPE appear in 3 – 6 days - Infected cells Round up &
become refractile & pyknotic.
• Isolated virus is identified and typed by neutralization
with specific antiserum.
36. B. Serology :-
• By CFT or
• Neutralization , using Paired serum samples.
IMMUNITY :
• Type specific
• Passive immunity is from mother to off spring during the
first 6 months of life.
• Ig M , Ig G – Blood
• Ig A, - Immunity against intestinal infection
37. Schema of the clinical and subclinical forms of poliomyelitis. This graphic representation
shows the presence of virus and antibodies in relation to the development and
persistence of the infection
38. PREVENTION & CONTROL :-
Nonspecific measures:
a. Safe drinking water,
b. improvement in sanitation,
c. food hygiene.
Vaccination: Both live and killed vaccines
1. Killed vaccine- SALK parenteral vaccine
2. Live attenuated vaccine- SABIN oral vaccine
40. live attenuated vaccine :- sabin’s 1959
• grown in primary or human diploid cell cultures.
• Stabilized by Mg Cl₂ and kept at 4 ͦC for weeks.
• Live vaccine multiplies infects and Immunizes
• progeny of vaccine Virus are disseminated in the
community.
• Multiple doses to establish permanent immunity
• Up to 5 doses 4 weeks apart
41. • Ig M & Ig G antibodies and Ig A antibodies in the
intestine.
• OPv contains :-
Type A virus : 10 lakhs TCID50 per Dose(0.5ml)
Type 2 virus : 2 lakhs
Type 3 virus : 3 lakhs
• Shelf life 4-8 ͦc 4months, -20 ͦc for 2yrs.
• Failure of cold chain
42. Live oral attenuated polio vaccine:-
Given orally
0 dose at birth
1st dose 6th wk.
2nd dose 10th wk.
3rd dose 14th wk.
4th dose between 16 – 24th month.
5th dose 5 yrs of age.
43. Property Sabin’s vaccine Salk’s vaccine
Immunising agent Live, attenuated Killed virus
Route of Oral Parenteral
administration
Immunity Mucosal (IgA) & Only humoral
Humoral (IgG,IgM,)
Reversion of virus Yes No
to virulent
44. Relative merits of killed and live vaccines :-
Safety :-
Attenuated strains:- Tend to acquire Neurovirulence
OPV : Not safe in immunodeficient
Efficiency :-
Interference
Diarrhoeal diseases
Breast feeding
Ease of administration :
OPV is preferable .
45. Economy :-
Live vaccine is very much economical.
Nature of immunity :-
Killed – systemic
Oral – local and systemic
Duration of immunity :-
Killed – booster doses necessary
Live – More lasting
Use in epidemics :-
OPV early during an epidemic
Pulse polo campaign Global eradication
46. VACCINE-ASSOCIATED PARALYTIC POLIOMYELITIS
• The only adverse reaction associated with OPV is the rare
occurrence of VAPP, which affects approximately 1 person/2.6
million OPV doses distributed.
• For immunocompetent patients, the clinical features and
outcome of VAPP differ little from disease caused by naturally
occurring polioviruses.
• More than 80% of recipient and contact cases are associated
with the first dose of OPV.
• OPV virus types 3 and 2 are more common causes of VAPP
than type 1.
47. EPIDEMIOLOGY :-
• 3 epidemiological phases :
Endemic
Epidemic
Vaccine era
• Improved systems of hygiene and sanitation
Promoted the transition from endemic to epidemic
.
48. • Human are the only known reservoir
• Children are more susceptible
• transmitted through feco-oral route.
• 80% cases occur before age of 3 yrs.
49. Factors infuencing incidence of paralysis
1. Pregnancy carries increased risk of paralysis.
2. Tonsillectomy during incubation period- bulbar
paralysis.
3. Injecting triple vaccine prepared using alum leads to
paralysis of involved limb.
4. Severe muscular exertion/trauma during pre
paralytic stage increases risk of paralysis
50. Treatment :
• Specific antiviral drugs for the treatment of
poliomyelitis are not available,
• therefore management is supportive and directed to
relief of symptoms
51. Global Eradication of poliomyelitis:-
• Eradication is possible.
• WHO has started the programme on 1988.
• Aimed to eradicate the disease by 2000.
• Poor progress in many countries a set back.
• PULSE immunization : vaccine to all children in a region on a
same day.
53. INDIA :
• 2006 – 60 cases were reported
• 2011 till date only 1 case is reported West Bengal.
Pulse polio immunization
• OPV is given to children of 0-5 years age on single
day, regardless to previous immunization
• 2 rounds – 4-6 weeks apart
• During low transmission season – nov - feb
