Major target tissues of viral disease

Clinical Virology
Viral infection of the Cardiovascular
system
Picornavirus

blood
Dr.

picornavirus 2

NPC & lymphoma

Adenovirus, HIV,
Parovirus B19, CMV

3 4
 Picornaviridae:
Enterovirus
Dengue virus

Flaviviridae
& Rhinovirus
+ss RNA
Enveloped virus

Filoviridae Morphology:
+ss RNA;Enveloped virus
Arenaviridae 1. Positive (+) single-stranded RNA
-ss RNA;Enveloped virus
Hantavirus Hantavirus Pneumonia & Inhalation of No specific Rodent
2. Naked icosahedral symmetry
pulmonary hemorrhagic viruses in dried treatment control
syndrome
Or
fever urine & feces
from infected
3. Replication occurs in the cytoplasm
Hemorrhagic Bunyaviridae small rodents
fever with -ss RNA
renal
Enveloped virus
syndrome
5 6

Picornaviridae Picornaviridae
Medical Microbiology
Murray et al.

Enteric cytopathic human orphan

X
1969 33

Hepatovirus
HAV (Enterovirus 72)

Parechoviruses: echoviruses 22 & 23

7 8
Picornavirus Genera (> 12 ) Enterovirus (
)
Aphthovirus c.1978 Former species name Current species name (2013/2)
Avihepatovirus August 2009 Human enterovirus A (HEV) "Enterovirus A"

Cardiovirus c.1978 The International Human enterovirus B "Enterovirus B" : CV, EV

Human enterovirus C* "Enterovirus C" : CV, PV
Enterovirus c.1971 Committee Human enterovirus D "Enterovirus D"
Erbovirus on Taxonomy of Bovine enterovirus "Enterovirus E"
Hepatovirus c.1991 Viruses (bovine enterovirus group B) "Enterovirus F"
Porcine enterovirus B "Enterovirus G"
Kobuvirus (ICTV) Simian enterovirus A "Enterovirus H"
Parechovirus 1996
(unassigned simian enteroviruses) "Enterovirus J"
Sapelovirus August 2009 Human rhinovirus A (HRV) "Rhinovirus A"
Senecavirus August 2009 Human rhinovirus B "Rhinovirus B"
Teschovirus Human rhinovirus C "Rhinovirus C"
Tremovirus August 2009
9 10

Parechovirus Picornaviridae:
The species Human parechovirus (proposed new Enterovirus 12
species name "Parechovirus A") consists of 16 types,
HPeV-1 to 16. HPeV-1 and HPeV-2, were formerly & Rhinovirus
classified in the enterovirus genus as echovirus 22
and 23, respectively. Another isolate, CT86-6760,
originally classified as E-23/HPeV-2 (based on
serological cross-reactions) has been re-classified
as HPeV-5.
Morphology:
-1999 defined 1. Positive (+) single-stranded RNA
-VP, VP1, VP3 2. Naked icosahedral symmetry
-acquired in early childhood.
12 Pentamers (5 protomeric unit)
-replicate in respiratory & gastrointestinal tract
-cause diseases similar to other enterovirus Protomer:VP1-4 (VP0+VP1+VP3)
11
3. Replication occurs in the cytoplasm 12
 Figure 361.

Replication: binding & entry

Genome of picornavirus

Linear single-stranded RNA, positive sense

7-8.5 kb

Viral protein VPg covalently bound to 5 end Viral protein linked to the genome

Short, genome-encoded poly(A) tail at 3 end
5 UTR
Viral
protein
linked
to the genome

ICAM-1 & Rhinovirus

Model for entry of picornavirus RNA:

Structural proteins Binding lead to rearrangement
IRES

2011 John Wiley & Sons, Inc. All rights reserved. 13 Drug: WIN52084; pleconaril 14

Figure 363.

Cell receptors and co-receptors used by Replication of Picornavirus

some picornaviruses

PVR

3D

RNA-dep RNA pol

3D

2011 John Wiley & Sons, Inc. All rights reserved. 15 Lysis 16
Genomic Organization and Proteolytic Proposed mechanism for replication
Processing of Poliovirus of picornavirus RNA
RNA synthesis is primed by VPg covalently
bound to uridine residues
Uridylylation of VPg
VPg
allows it to
hybridize to the
poly(A) tail and
Protease 2A: serve as a primer
Cleave the for (-) strand
p220 subunit -RNA
synthesis
of cap binding
complex RNA synthesis is
CPE completed by 3D
(RNA-dep RNA pol)
Proteinases: L, 2A, 3CD, and 3C
VPg
L is found on the N-terminus of only Foot-and-mouth disease virus polyprotein. +RNA
2C (ATPase); 3D (polymerase)
Reproduced from Virus Research, Vol. 111, Mueller, S.,
Wimmer, E., and Cello, J., Poliovirus and poliomyelitis: A tale of guts, brains, and an accidental event, pp. 175193, Copyright 2005, with permission from Elsevier
17 2011 John Wiley & Sons, Inc. All rights reserved. 18

Rhinovirus (HRV
RV)
Parechovirus
Diseases: pathogenesis
Common cold & upper respiratory tract
1-16 infection
Exacerbations of asthma and chronic
obstructive pulmonary disease (COPD)

Characteristics:
1. 3 species: A (80 serotypes), B (32
serotypes), C (54 serotypes); >150
serotypes
2. labile to acidic pH
3. 33
Transmission:
Respiratory secretions
Virus contaminated fingers
Control: no vaccine
19 Treatment: no anti-viral drugs 20
 Enteroviruses (EV)
Picornaviridae family
Naked capsid virus
Ubiquitous in nature
Entero means intestine
EV A-D
Five groups of enteroviruses:

Polioviruses
Nonpoliovirus

Group A Coxsackieviruses

Group B Coxsackieviruses

Echoviruses

new enterovirs
21 22

Enterovirus A-D Enteroviruses

At least 70 enteroviruses are known to infect humans.
The majority of enterovirus infections are
asymptomatic or cause mild or self-limiting
EV-A
infections in children.
20 recognizable clinical syndromes
EV-B Some cause myocarditis and dilated cardiomyopathy
(DCM) [direct viral damage & /or the consequences
of immune response].
EV-C 70% of the general population has been exposed to
cardiotropic viruses.
EV-D About 14%21% of respiratory disease is associated
with enterovirus infections.

23 24
 Medical microbiology
(Murray)

Medical microbiology
29th ed, (Brooks)

: 1998Enterovirus 71 :
: 1998 : 400
400
78
78
78 25 26

Pathogenesis of enterovirus
Transmission

EV71

EV71
EV71

27 28
 Stability of Enteroviruses in
the Environment
Resistant to
pH levels less than 3 (stomach acid)
Digestion by most proteases
Detergents
70% alcohol
Solvents (e.g., ether and chloroform)
Disinfectants (e.g., 5% Lysol, 1% QUATS)
May be stable several days to several weeks at
4oC (39.2oF)

29 30

Inactivation/Disinfection Poliovirus

Protocols Diseases:
1.Asymptomatic infection: 90-95%
of all poliovirus infections
Chlorine (bleach)
2.Mild febrile illness: often occurs
Hydrochloric acid in infants in less developed nations
Aldehydes 3.Aseptic meningitis: fever and stiff
Heat 50oC (122oF) for one hour (in neck. Recovery in one week
the absence of calcium and 4. Paralytic poliomyelitis
magnesium) 5. Post-Polio Syndrome (PPS):Muscle
fibers of surviving motor neurons
slowly deteriorate over time.

31 32
Poliovirus pathogenesis Progression of poliovirus infection

Transmission:
A. Fecal-oral Asymptomatic;
B. Respiratory minor or major
secretions disease

Or neuronal spread small intestine

Peripheral nerve  central nervous system
 Motor neuron cells

33 34

Small Percent of Patients Laboratory Diagnosis of Poliovirus

Infections
Polioviruses carried via the
bloodstream to the anterior horn Most common method: isolate virus from
cells of the spinal cord stool samples

Results in lesions in the spinal cord and brain Grows well in characterized in any human

Motor neuron destruction or monkey kidney cell lines (causes good
Paralysis
Paralysis CPEs)
Respiratory arrest Identify serotype with neutralization
Death assays
Nucleic acid methods (RT-PCR): genomic
sequencing to determine if the infection is
caused by vaccine or wild-type virus
15 35 36
Prevention of Poliovirus Incidence of polio in the united States.
Vaccine:
1.Salk(
vaccine: formalin-killed
)
polio virus that is injected 1955
subcutaneously
2.Oral polio vaccine (developed by Sabin
attenuated (non-virulent) polio
): 1961/62

virus is ingested

37 38

39 40

Progress Towards Poliovirus

Eradication

Significant progress between 1988 and

2003
IPV
OPV
2003 reduced from 125 to 6 polio-

3
99


b




endemic countries
DaPT-Hib-IPV

IPV

New pockets of cases in as many as 26

2
4
6
countries that had been polio-free

WHO intensifying efforts
1


OPV
Educational programs to reinforce the

importance and safety of vaccination

41 42

Endemic Polio Coxsackie virus

2015 ? Named after the town of Coxsackie, New
York
A & B groups: biological & antigenic
differences
Transmission:
A. Fecal-oral
B. Respiratory secretions
Diseases: Asymptomatic infection
1.A & B: "Cold, rashes, viral meningitis
fever, sore throat
2 A: Herpangina
:
and small red-based vesicles over the back of the
patient's throat
3.A: Hand Foot and Mouth Disease: occurs in
Courtesy of the World Health Organization
children less than 5
43 4. B: Myocaritis/percarididtis; Pleurodynia; DM 44
Potential fate of cardiomyocytes after virus infection of the heart
Pathogenesis of viral myocarditis.
Coxsackie virus group B

Dilated cardiomyopathy (DCM)

Trends in Molecular Medicine 2012; 18: 426-437.
Future Microbiol. 2011 May ; 6: 551566. 45 46

Echovirus Anti-enterovirus drug

Enteric cytopathic
human orphan;
diseases x
Transmission:
A. Fecal-oral
B. Respiratory secretions

Pleconaril binding x
47 48