Download Positive (+) RNA Viruses

VIROLOGY
Positive (+) RNA
Viruses
SAMUEL AGUAZIM M.D.
Lange Chapter 40
Definition of Positive (+) RNA Viruses
Viruses whose genomic RNA either can serve
directly as mRNA (all + RNA viruses except the
retroviruses)
OR has the same sequence as the mRNA
(retroviruses)
Characteristics of (+) RNA Viruses
Naked (+) RNA is infectious
Positive RNA Viruses (except retroviruses)
replicate in the cytoplasm
No (+) RNA virus is segmented
The retrovirus are diploid (two copies of the
chromosome)
Most RNA viruses are Enveloped. The
exception are the smallest-the caliciviruses
and picornaviruses.
Family Picornaviridae
Small, naked viruses with +RNA genome.
Two major groups
Enteroviruses – Acid stable, infect GI tract mainly transmitted
feco-orally
Polio viruses (Type 1,2 & 3)
Coxsackie viruses
A (21 serotypes)
B (6 serotypes)
ECHO viruses (34 serotypes)
New enteroviruses (strain 68,69,70,71 & 72)
Rhinoviruses – Acid labile, infects upper respiratory tract,
transmitted by inhalation of droplets.
Family Picornaviridae
(Enteroviruses)
Poliovirus
Echovirus
Enteroviruses 68-71
Coxsackievirus A & B
Rhinoviruses
Hepatitis A
(mnemonic: PEECoRnA)
Table 3 Properties of Rhino- and Entero-viruses
Optimum
Site of
pH
Detergent Sero Transgrowth
primary
sensitivity
sensitivity types mission
temperature
infection
Rhino labile to
viruses acid pH
33 degrees
C (approx)
Entero resistant to 37 degrees
viruses acid pH
C (approx)
>100 aerosol
Resistant
72
upper
respiratory
tract
oro-fecal gut
Genera that infect humans
Enterovirus
Polio
Coxsackie A and B
Echo
Other enteroviruses
Diseases of the human (and other)
alimentary tract (e.g. polio virus)
Rhinovirus
Disease of the nasopharyngeal region (e.g.
common cold virus)
Hepatovirus
Human hepatitis virus A
Parechovirus
Formerly echoviruses 22 and 23. Disease
of alimentary and respiratory tract
Table 4 Human diseases caused by enteroviruses
Poliovirus
Coxsackie A
virus
Coxsackie B
virus
Echovirus
Enterovirus
(other)
Asymptomatic
infection
yes
yes
yes
yes
yes
Meningitis
yes
yes
yes
yes
yes
Paralysis
yes
yes
yes
yes
no
Febrile
exanthems
no
yes
yes
yes
yes
Acute
respiratory
disease
no
yes
yes
yes
yes
Myocarditis
no
yes
yes
yes
no
Orchitis
no
no
yes
yes
no
POLIO
case
A 6 year old child, female, developed flulike illness, and was managed
symptomatically.
10 days later, she developed weakness of
her left leg, which progressed to complete
paralysis.
Sensation was normal. The other
extremities were normal. Respiration was
also normal.
case
She was diagnosed with
a viral illness, and
underwent a series of
physical therapy,
however, the affected
limb became shorter
and smaller.
Surgery was done to
facilitate mobility.
CASE
Impression: Poliomyelitis
Poliovirus
Transmission is fecal-oral
Close to being eradicated through the use of the oral
(attenuated) Sabin or the killed (Salk) vaccines.
Virus infects oral and gastrointestinal epithelium
>90%of the infections are asymptomatic
When the virus infects the anterior horn cells of the
spinal cord (1in 250 infections), poliovirus may cause
a paralytic disease involving the cranial and
respiratory nerves.
POLIOVIRUS:
Most infections (greater than 90%) are asymptomatic, disease may appear as:
a. Abortive poliomyelitis: (minor illness)
The first symptomatic result of polio infection is febrile disease (fever) and
occurs in the first week of infection. The patient may exhibit a general malaise
which may be accompanied by vomiting, a headache and sore throat.
b. Nonparalytic poliomyelitis: Three or four days later a stiff
neck and vomiting, as a result of muscle spasms, may occur in about 2% of
patients. The virus has now progressed to the brain and infected the meninges.
c. Paralytic poliomyelitis: In bulbar paralysis cranial nerves and
the respiratory center in the medulla are affected leading to paralysis of neck
and respiratory muscles. There is no sensory loss associated with the paralysis.
The degree of paralysis may increase over a period of a few days and may remain
for life or there may be complete recovery over period of 6 months to a few
years. In bulbar poliomyelitis, death may also ensue in about three quarters of
patients, especially when the respiratory center is involved. Patients were able
to survive for a while using an iron lung to aid respiration (figure 4).
figure 4 .Paralyzed child in an iron lung
Child with polio © WHO
Live (Sabin) vaccine:
1. Advantages:
induces secretory antibody response (IgA) in addition to
IgG;
oral delivery easily administered;
long duration of immunity;
indirect immunization in community by circulation of
attenuated vaccine virus; eliminates circulation of ‘wildtype’ polio.
2. Disadvantages:
vaccine associated polio in vaccine recipients and
contacts;
reversion of virus to virulence; requires refrigeration;
unsafe for immunodeficient patients.
Inactivated (Salk) vaccine:
1. Advantages:
No risk of poliomyelitis in vaccinees or contacts;
incorporated into routine immunizations (DPT);
good stability in storage and transport;
safe for immunodeficient patients; no concern about
reversion.
2. Disadvantages:
No local immunity in gut;
doesn’t stop circulation of wild-type polio therefore
need high levels of community immunization;
injection more expensive than oral administration; need
booster doses.
POLIOVIRUS VACCINE:
Current practice in the United States is to give:
four immunizations of the inactivated vaccine
One booster if you travel to endemic areas.
The inactivated vaccine induces antibodies,
which can prevent virulent revertants in the live
vaccine from causing paralytic poliomyelitis.
Immune globulins are available but rarely used.
Echovirus: Enteric Cytopathogenic Human
Orphan viruses
Highly infectious, and its primary target is children.
The echovirus is among the leading causes of acute febrile illness in
infants and young children
most common cause of aseptic meningitis.
Infection within the first two weeks of birth can cause devastating
and potentially fatal disease.
In this population, death usually results from overwhelming liver
failure or myocarditis, rather than infection of the central nervous
system.
can mimic symptoms caused by other common bacterial and viral
infections, so echovirus infections are often treated with therapies
aimed for other infections.
evolution of antibiotic resistant bacteria.
Main causes of infection are from overcrowded conditions such as
the poor districts of a city and poor hygiene.
Occurs disproportionately in males
Other Enteroviruses
Enterovirus 70 is the causative agent epidemics
of acute haemorrhagic conjunctivitis that swept
through Africa, Asia, India and Europe from 1969
to 1974.
The virus is occasionally neurovirulent.
Enterovirus 71 appears to be highly pathogenic
and has been associated with epidemics of a
variety of acute diseases, including aseptic
meningitis, encephalitis, paralytic poliomyelitislike disease and hand-foot-mouth disease.
Enterovirus 72 is the designation assigned to
hepatitis A virus
ACUTE HEMORRHAGIC CONJUNCTIVITIS
Coxsackie Virus A
(mainly serotype A 16) cause herpangina(fever, sore
throat and tender vesicles in the oropharynx). Hand,
foot, and mouth disease(painful blisters in the mouth,
throat, hands, feet, or in all these areas).
is the common name of this viral infection.
Aseptic Meningitis
Acute lymphoglandular pharyngitis
Common cold
usually occurs in children, but adults can also develop
the condition.
should not be confused with the “foot and mouth
disease" usually found in animals with hooves (for
example, cattle, pigs, and deer).
Type A also causes conjunctivitis (inflammation of the
eyelids and white area of the eye).
Hand, Foot and Mouth Disease
Hand, Foot and Mouth Disease
Coxsackie Virus B
Bornholmes disease (a.k.a, pleurodynia or
Devil’s grip; severe intercostal pain and fever in
many areas.
Sufferers of chest pain should see a doctor
immediately
myocarditis or pericarditis, which can result in
permanent heart damage or death.
Aseptic Meningitis
As a group, they are the most common cause of
unexpected sudden death, and may account for
up to 50% of such cases.
illness may last for up to two weeks, but may
resolve as quickly as two days.
Infection usually occurs between the months of
June and October.
Rhinovirus
Major causative agent of the common cold
Over 100 serotypes
The cell surface receptor is ICAM-1.
Transmission: Respiratory
Peak in the summer and early fall
Not resistant to stomach acid
Grows 33 degrees Celsius
Family Caliciviridae
Norwalk Agent Gastroenteritis
-”a.k.a Norovirus”
- Noninflammatory diarrhea found
in
older children and adults.
- Fecal-oral in shellfish food or
water
- 1-2 day incubation and 1 day of
vomiting, diarrhea and low grade fever.
 Hepatitis E – see Hepatitis lecture
Family Flaviviridae
- Are enveloped,icosahedral (+) RNA viruses (Flavi
means “yellow”)
Hepatitis C – see lecture on hepatitis viruses
Yellow Fever Virus
Dengue Virus ( Mc)
St. Louis Encephalitis Virus
West Nile Virus
Yellow Fever Virus
Tropical South America and Africa
Spread by mosquitoes
Arthropod-borne virus = arbovirus
Febrile disease of varying severity
Often includes hepatitis and may progress to
hemorrhagic fever( Fever plus Black Vomitus)
Liver Biopsy Reveals COUNCILMAN BODIES
Live Attenuated vaccine
Dengue Virus (breakbone disease)
Arbovirus
Spread by the Aedes mosquitoes in the tropics,
including the Gulf Coast of the United States.
Rapid onset, with fever, severe myalgias, arthralgias,
headache, and rash.
Four serotypes
Dengue hemorrhagic shock syndrome (DHHS) is a
serious complication seen in young babies with
maternal antibodies or in any individual with
antibody from a previous infection who is infected
with a second dengue serotype.
St. Louis Encephalitis Virus
Spread by the Culex mosquito
endemic in Canada, the South Eastern United
States , the Caribbean, and South America.
Most severe in the elderly often present
with global brain involvement such as
tremors and cranial nerve dysfunction.
St. Louis and West Nile encephalitis are
the two most common causes of arboviral
encephalitis.
West Nile Virus
Spread to the western hemisphere in 1999
most commonly diagnosed arbovirus in the
United States
now a major mosquito-borne infection of birds,
horses and humans
Thousands have been infected but deaths have
occurred mainly in the debilitated elderly
persons.
In addition to the encephalitis, there may be
muscle weakness and flaccid paralysis
Family Togaviridae
Enveloped, icosahedral
Western, Eastern, and Venezuelan equine
encephalitis viruses, Chikungunya
WEE: is most prevalent to western and central
United States and Canada.
EEE: is most prevalent in swampy areas of the
United States eastern coast.
VEE: most prevalent in Venezuela, Colombia,
Central America, and Texas.
Rubella Virus “German Measles”
Western, Eastern, and Venezuelan
equine encephalitis viruses
Horses are the dead-end hosts
Wild Birds are the normal hosts
Mosquitoes transfer the disease to humans
Disease: Encephalitis
Presentation
Headache
Nausea
Vomiting, fever
Changes in metal status ( confusion, stupor)
Rubella Virus “German Measles” or 3-days
Measles
transmission: respiratory droplets and
transplacentally
Discrete red maculopapular rash
Mild fever
Can cross the placenta and cause serious birth
defects, such as cataracts, patent ductus
arteriosus and Sensorineural deafness(known as
the Rubella Triad).
Vaccine MMR (measles, mumps & Rubella) is a
single attenuated strain of rubella virus.
Recommended that barrier protection be used to
prevent pregnancy for 16 weeks after
vaccination.
maculopapular rash beginning on
the face and spreading to the
extremities.
Infant with congenital rubella
syndrome.
The common clinical presentation
in pregnant women infected with
rubella during the first trimester
includes a maculopapular rash
along with postauricular and
suboccipital lymphadenopathy.
Congenital rubella occurs when
a pregnant woman is infected
with rubella during the first
trimester, and the virus infects
fetal cells transplacentally
For normal lab values:
http://www.usmle.org/step1/2005Step1.pdf
Coronavirus
First isolated from chickens in the 1930s, coronaviruses are
known to be pathogenic for many animal species.
Outbreak of coronavirus pneumonia (CVP), also known as
Severe Acute Respiratory Syndrome (SARS) in February
2003.
Researchers at Hong Kong University recently identified a
new coronavirus as the cause.
Structure:
Spherical or pleomorphic enveloped particles
containing single-stranded (positive-sense) RNA associated
with a nucleoprotein within a capsid comprised of matrix
protein.
The envelope bears club-shaped glycoprotein projections.
Two serotypes called ( 229E & OC43)
Receptor for SARS( angiotensin-converting enzyme-2)
SARS Virus
Transmission:
enters the body through the eyes, nose and mouth.
An important route seems to be touching objects that are contaminated with
viruses.
Close person to person contact seems important for efficient spread.
gets their name from their striking corona (crown) of spikes made of S
glycoprotein.
These spikes bind to host cells and allow the virus to enter the cell.
The virus is enveloped
SARS Virus
The
spike
Symptoms of SARS:
begins with a fever (measured
temperature greater than 100.4°F [>38.0°C]).
chills or other symptoms, including headache,
general feeling of discomfort and body aches.
Some people also experience mild respiratory
symptoms at the outset.
After 2 to 7 days, SARS patients may develop a
dry, nonproductive cough that might be
accompanied by difficulty breathing and
atypical pneumonia.
SARS: Diagnosis/Evaluation
Initial diagnostic testing for suspected SARS
patients should include:
chest radiograph
pulse oximetry
blood cultures
sputum Gram's stain and culture
Testing for viral respiratory pathogens, notably
influenza A and B and respiratory syncytial
virus.
A specimen for Legionella and pneumococcal
urinary antigen testing should also be
considered.
For individuals who must travel to a
SARS-affected area:
CDC advises that travelers in a SARSaffected area should wash their hands frequently
to protect against SARS infection. In addition,
CDC advises that travelers may wish to avoid
close contact with large numbers of people as
much as possible to minimize the possibility of
infection.
For individuals who think they
might have SARS:
People with symptoms of SARS (fever greater than
100.4°F [>38.0°C] accompanied by a cough and/or
difficulty breathing) should consult a health-care
provider.
To help the health-care provider make a
diagnosis, tell them about any recent travel to
places where SARS has been reported or
whether there was contact with someone who
had these symptoms
VIRUS
FAMILY
RNA
VIRION
STRUCTUR ASSOCIAT
E
ED
POLYMER
ASE
ENVELOPE SHAPE
REPLICAT
E IN
MAJOR
VIRUSES
calici
Ss+RNA
linear non
segmented
No
Naked
Cytoplasm
norwalk
Hepe virus
“”””’’’’’
“”’’’
Picorna
“””””’’’
“”””””””””””””
Icosahedral
Hep E
“”””””””””””
“””””””””””””
“””””””””””
Polio
Echo
Enterovirus
Coxsackie
Hep A
VIRUS
FAMILY
RNA
VIRION
STRUCTUR ASSOCIAT
E
ED
POLYMER
ASE
ENVELOPE SHAPE
REPLICAT
E IN
MAJOR
VIRUSES
Flavi
Ss+ RNA
linear nonsegmented
No
Enveloped
Icosahedral
Cytoplasm
Yellow
fever,
dengue,
SLE , hep c
Toga-virus
“””””””””””””
“”””””””””””
“””””””””””
“”””””””””
“”””””””””
Rubella.
WEE.
EEE,VEE
CORONA
“”””””””””
“”””””””””””
“””””””
HELICAL
“””””””””””
CORONA
RETRO
DIPLOID
Ss+RNA
LINEAR
nonsegmented
Yes,
RNA
DEPENDE
NT
DNA
POLYMER
ASE
“””””””””””””
ICOSAHED NUCLEUS
RAL OR
TRUNCATE
D
HIV’
HTLV.
SARCOMA