Download PICORNAVIRIDAE

PICORNAVIRI
DAE
By Adey Berhanu
Source: http://www.virology.net/Big_Virology/EM/polio1.gif
Introduction
 Characteristics of Picornaviruses
 Genera
 Replication
 Epidemiology
 History
Viral Profiles
 Polio
 Rhinoviruses
New Findings
Drug Profile
Links
Resources
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_I8S2jVM: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 negativesense 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 13.
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 United States peaked with
over 21,000 paralytic cases.
- 1955: The Salk vaccine licensed in the United States.
- 1961-1962: The Sabin vaccine licensed in the United
States.
- 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 United States: the Salk vaccine (IPV)
and the Sabin vaccine (OPV), but only one is used.
-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 United States vaccination schedule of children.
Primary vaccination with three subcutaneous doses is
recommended for unimmunized children and adults.
A
booster dose is recommended for children. Protection is
believed to be a duration of 5 years, possibly longer.
-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 Japan infants. The article investigates 3 additional cases of
neonatal sepsis human parechovirus 3 in Canadian newborns.
The three cases were similar in that the infants were
hospitalized with high fever, erythematous rash, tachypnea for
several days. Viruses removed from the nasopharyngeal tissue
had viral proteins closely related to three serotypes of the
human parechovirus. Therefore, this report presents three
other confirmed cases of human parechovirus outside of
Japan and the first description of neonatal sepsis caused by
human parechovirus serotype 3.
- 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. 7 Nov 2005. M510362200.
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 replicationcompetent 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. 19 April 2004. Pg. 835-852.
DRUG PROFILE
Ganciclovir
Source: http://virology-online.com/general/ganciclovir.gif
Gangciclovir, 9-[(1,3-dihydroxy-2propoxy)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/n
on-polio_entero.htm
- Hepatitis A:
http://www.cdc.gov/ncidod/diseases/hepatitis/a/ind
ex.htm
RESOURCES:
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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. 19 April 2004. Pg. 835-852.
Isselbacher, Kurt J, et al. Harrison’s Principles of Internal Medicine. 13th edition.
New York: McGraw-Hill, Inc, 1994.
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Knipe, David, et al. “Picornaviridae.” Fields Virology. 4th ed. Lippincott Williams &
Wilkins: Philadelphia, 2001.
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. 7 Nov 2005. M510362200.
“Poliomyelitis.” Center for Disease Control and Prevention.
<http://www.cdc.gov/nip/publications/pink/polio.pdf>