PICORNAVIRIDAE
By Adey Berhanu
Source:
http://www.virology.net/Big_Virology/EM/polio1.gif
INTRODUCTION
CHARACTERISTICS
OF PICORNAVIRUSES:
The
picorna viral family derives its name from the words:
pico which
means small, and rna
which stands for ribonucleic acid. The
root of its name is appropriate because the viruses in the picornaviridae
family are small RNA viruses. The virions are approximately 30nm in diameter and the genomes
are roughly 7.0-8.5 kilobases. These viruses are
infectious and range in the seriousness of disease. The The viruses of
the picornavirdae family are classified together by
following characteristics. Picornaviruses are single-stranded, positive sense RNA
viruses. The virions
are non-enveloped with icosahedral morphology. The genome is monopartite
and has internal ribosome entry sites (IRES).
Translation and cleavage result in 11 or 12 different proteins as
products.
GENERA:
The
members of the picornaviridae are classified in 5
genera, four of which can cause disease in humans.
-
Enteroviruses
polioviruses 1-3,
Human coxsackiviruses, Human echoviruses
-
Rhinoviruses
Human rhinoviruses 1-103
-
Hepatoviruses
Human hepatitis A virus
-
Parechoviruses
Human parechoviruses
1-2
-
Aphtoviruses
Infects animals such as cattle, goats, pigs,
sheep, and rarely humans
-
Cardioviruses
Infects rodents and rarely humans
Source:
http://images.google.com/images?q=tbn:Qi9bq_I8S-2jVM:http://www.qub.ac.uk/afs/vs/vsd16d.jpg
REPLICATION:
The
replication cycle can be summarized in the following steps.
1.
Virus
binds to cell receptor and the genome is uncoated.
2.
The
virion protein is removed and the viral RNA is
translated.
3.
The
polyprotein is cleaved to produce distinct viral
proteins.
4.
Viral
RNA polymerase copied to produce the negative-sense RNA strand.
5.
The
negative-sense RNA strands are ultimately copied to produce more
positive-sensed RNA strands.
6.
In
later infection, the positive-sense RNA strands enter the morphogenetic
pathway.
7.
Cell
lysis occurs releasing newly synthesized virus
particles.
EPIDEMIOLOGY:
For
the most part, the picornaviruses have world wide
distribution. Transmission most commonly
occurs via the fecal-oral route or respiratory route depending on the specific
virus.
HISTORY:
-
In
1898, the first animal virus to be discovered was the foot-and-mouth disease
virus which is a picornavirus.
-
The
poliovirus was first isolated and identified in 1908.
VIRAL PROFILES
POLIO
Source:
http://www.ecbt.org/images/PolioL.jpg
As
a member of the enterovirus genus, polio can be
considered among the most important.
Beginning with the epidemics in the early 1800s, polio has presented itself
as a serious public health issue. The poliovirus has three serotypes:
poliovirus 1-3.
HISTORY:
-
2000
B.C.: Egyptian depictions of a young man with an atrophied limb believed to
represent poliomyelitis.
-
1800s:
First clinical descriptions of poliomyelitis including cases of paralysis with
fever.
-
1952:
Polio epidemic in the
-
1955:
The Salk vaccine licensed in the
-
1961-1962:
The Sabin vaccine licensed in the
-
1988: The World Health Organization launched a
global polio eradication campaign
EPIDEMIOLOGY:
The
poliovirus is considered to be highly infectious. Humans are the only known reservoir for the
poliovirus. Transmission of the
poliovirus is via the fecal-oral route. In temperate climates poliovirus infection
commonly peaks during the summer months.
The poliovirus has world wide distribution, however, since the advent of
the vaccine poliovirus infection is extremely low in developed countries and
cases are now highly concentrated in developing countries.
PATHOGENESIS:
The
virus enters the body via the alimentary canal.
Primary replication of the virus takes place in the throat (pharynx) and
gastrointestinal tract. During viral
shedding, before the onset of illness, the virus can be found in the throat and
feces. The virus then invades the blood
stream where it can infect the lymph tissue and possibly cells of the central
nervous system. In the case that the
poliovirus infects and replicates within the cells of the CNS such as the motor
neurons of the brain stem, the resulting destruction is a manifestation of
poliomyelitis. The polioviruses have a
tropism for the cells of the central nervous system.
CLINICAL
MANIFESTATIONS:
The
incubation period for the polioviruses can be between 4 to 35 days though in
most cases it is between 7-14 days. Most
infections are asymptomatic or inapparent.
The following clinical manifestations of disease can be divided into
three categories: abortive poliomyelitis, aseptic meningitis, and paralytic
poliomyelitis.
Abortive
poliomyelitis: This is a mild, non-specific illness. Manifestation of disease is characterized by
a 2-3 day fever and influenza-like symptoms.
There are no signs of CNS localization and complete recovery can be expected
in less than a week.
Aseptic meningitis: Symptoms include stiffness of the neck, back,
and/or legs and last from 2 to 10days.
Recovery is rapid and complete.
Paralytic poliomyelitis: Begins with 2 to 3 days of minor illness such
as fever and influenza-like symptoms.
After several days these symptoms disappear and return within 5 to 10
days along with signs of meningeal irritation.
Flaccid paralysis ensues characterized by cramping muscle pain, spasms, coarse
twitching, and tendon reflexes are diminished. Encephalitis is rare but
possible. Patients do not show loss of sense or cognitive changes. Recovery is possible however paralysis
lasting beyond 6 months is permanent.
TREATMENT & PREVENTION
Treatment of polio is supportive. There is no
effective antiviral therapy available.
Prevention of polio is possible via
vaccination. There are two licensed
vaccines in the
-The Sabin vaccine, a
live-attenuated virus, distributed orally (OPV) was discontinued in 2000 due to
its association with causing paralytic disease.
Source:
http://upload.wikimedia.org/wikipedia/en/9/9b/Stamp-ctc-polio-vaccine.jpg
- The Salk vaccine, an inactivated poliovirus
vaccine, (IPV) is recommended to prevent against polio. IPV contains all three serotypes of
poliovirus and is administered intramuscularly.
IPV is considered safe with no significant side effects. IPV is part of the
-In 1988 the World Health Organization
launched a global polio eradication campaign and it still remains one of the
organization’s priorities.
RHINOVIRUS
Currently,
there are 103 different rhinovirus serotypes.
EPIDEMIOLOGY:
Rhinoviruses
have world wide distribution and are extremely common. Rhinoviruses are transmitted via aerosol
droplets—virus-contaminated respiratory secretions.
CLINICAL
MANIFESTATIONS:
Rhinoviruses
are the most frequent cause of the “common cold.” The incubation period is between 1 to 4
days. The illness caused by rhinovirus
is mild and typical symptoms include nasal discharge, nasal secretions,
sneezing, and sore throat. In more serious cases fever and upper respiratory
infection are possible. Illness usually
resolves itself within a week.
TREATMENT
& PREVENTION
-There
are currently no antiviral therapies available. However, over-the-counter cold
remedies are useful in relieving the symptoms caused by rhinovirus.
-No
effective vaccine is available.
NEW FINDINGS
Implications of Cosxackie B virus infection and pancreatitis
This
article presents the result of a study investing the differences in morbidity
and mortality associated with the different routes of infection of the
Coxsackie B virus. Swiss albino mice were infected with either oral or intraperitoneal
(into the abdominal cavity) injection of Coxsackie B virus. The results showed that virus titres were higher in intraperitoneal infection versus oral
infection. Both routes showed infection
of the pancreas, however, only intraperitoneal injection showed damage to the
pancreas. In both routes of transmission the pancreatic islets were spared and
viral VP1, protein 3A, and alpha interferon could be found. The article concludes that the oral route of
infection restrains the pathology in the pancreas. Second, the Coxsackie B virus is associated
with the prolonged presence of alpha interferon. Therefore, the oral route of infection may
imply a natural way of investigating the relationship of enteroviruses
such as Coxsackie B virus in pancreatitis and type 1 diabetes mellitus.
-Bopegamage, Shubhada,
et al. “Coxsackie B virus infection of
mice: inoculation by the oral route protects the pancreas from damage, but not
from infection.” The Journal of general virology. (86): 2005. pg:3271
-3280.
Human Parechovirus 3
and neonatal infections
This
article investigates the details concerning the third serotype of the human
parechovirus that was recently isolated in
- Boivin, Guy et al.
“Human parechovirus 3 and neonatal infections.” Emerging Infectious
Diseases. (11): 1, Jan 2005. pg.
103-105.
Rhinoviruses and
asthma
This
article discusses how rhinoviruses may be associated with 60% of the viral,
upper respiratory tract infections involved in asthma exacerbations. It is believed that the rhinovirus has
specific pathological activity that results in the relapse of acute
asthma. Rhinovirus produces a
reactivation of asthmatic symptoms as well as a deterioration of respiratory
function and an increase in bronchial hyper-responsiveness. The cytotoxic
effect of the rhinovirus is believed to facilitate the penetration of
allergens. Therefore, through several
mechanisms the rhinoviruses have associated with triggering or exacerbating
asthma.
- Pelaia, Girolamo, et al. “Respiratory infections and asthma.” Respiratory Medicine. Nov 2005. doi:10.1016/j.physletb.2003.10.071.
Echoviruses
interaction with DAF
This
article analysis how the Echoviruses bind to the Decay Accelerating Factor
(DAF) in order to facilitate entry of the virus into the cell. In this specific article uses cryo-negative stain transmission electron microscopy and
three-dimension image reconstruction to investigate the binding of echoviruses
type 7, 11 and 12 to DAF. Results
indicate that the differences in interactions of the different serotypes is due
to small subtleties in structure rather than in large scale repositioning of
the virus surface.
- Pettigrew, David, et
al. “The Interactions of Echoviruses and Decay Accelerating Factor (DAF):
Structural and Functional Insights.” The Journal of Biological Chemistry.
Recombinant
poliovirus-SIV cocktails and HIV research
The
article proposes the use of the Sabin poliovirus
vaccine to research effective targets for HIV medications. Based on the Sabin
poliovirus vaccine, researchers have created replication-competent poliovirus
recombinants that express antigens derived from the simian immunodeficiency
virus (SIV). This recombinant poliovaccine is then
injected into mucosal tissue to observe the cellular immunity that is
induced. This recombinant poliovirus-SIV
vaccine has demonstrated protection against HIV infection and AIDS in cynomolgus monkeys.
- Crotty, Shane and Raul Andino. “Poliovirus vaccine strains as mucosal
vaccine vectors and their potential use to develop an AIDS vaccine.” Advanced Drug Delivery Reviews. (56):
6.
DRUG PROFILE
Ganciclovir
Source:
http://virology-online.com/general/ganciclovir.gif
Gangciclovir, 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine
Brand
name: Cytovene
Ganciclovir is an antiviral drug. Ganciclovir is an
analogue of acyclovir.
Mechanism:
Ganciclovir acts by inhibiting viral DNA polymerase
and can be incorporated into viral genome where it eventually terminates DNA
elongation.
Use:
Ganciclovir is used primarily to treat patients with
Cytomegalovirus (CMV) infection of the eyes.
However, this antiviral is also active against all herpes infections.
Administration:
Gancliclovir can only be administered intravenously.
Dosage: Initial therapy is 5mg/kg twice a day for 14
to 21 days followed by a dose of 5mg/kg five times a week.
Side
effects: headache, diarrhea, nausea, vomiting, upset stomach, loss of appetite,
dizziness. Also, associated with
profound bone marrow suppression, particularly neutropenia.
LINKS
-
Center for Disease Control and Prevention:
http://www.cdc.gov/
-
National Institute of Health: http://www.nih.gov/
-
Polio: http://www.cdc.gov/nip/publications/pink/polio.pdf
-
Enteroviruses:
http://www.cdc.gov/ncidod/dvrd/revb/enterovirus/non-polio_entero.htm
-
Hepatitis A: http://www.cdc.gov/ncidod/diseases/hepatitis/a/index.htm
RESOURCES:
· Boivin, Guy et al. “Human parechovirus 3 and neonatal infections.” Emerging Infectious Diseases. (11): 1, Jan 2005. pg. 103-105.
· Bopegamage, Shubhada, et al. “Coxsackie B virus infection of mice: inoculation by the oral route protects the pancreas from damage, but not from infection.” The Journal of general virology. (86)2005. pg:3271 -3280.
·
Crotty, Shane and Raul
Andino.
“Poliovirus vaccine strains as mucosal vaccine vectors and their
potential use to develop an AIDS vaccine.”
Advanced Drug Delivery Reviews. (56): 6.
·
Isselbacher, Kurt J,
et al. Harrison’s Principles of Internal Medicine. 13th
edition.
·
Knipe, David, et al. “Picornaviridae.” Fields Virology. 4th ed.
Lippincott Williams & Wilkins:
·
Pelaia, Girolamo, et al. “Respiratory infections and asthma.” Respiratory
Medicine. Nov 2005. doi:10.1016/j.physletb.2003.10.071.
·
Pettigrew, David, et al.
“The Interactions of Echoviruses and Decay Accelerating Factor (DAF):
Structural and Functional Insights.” The Journal of Biological Chemistry.
· “Poliomyelitis.” Center for Disease Control and Prevention. <http://www.cdc.gov/nip/publications/pink/polio.pdf>