Transcript Parainfluenza Viruses

CORONAVIRIDAE
Introduction
• Coronaviruses are named for the solar corona–like
appearance (the surface projections) of their virions
when viewed with an electron microscope.
• Coronaviruses are the second most prevalent cause of
the common cold (rhinoviruses are the first).
• Coronaviruses infect humans, animals, and birds.
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Peplomer: glycoprotein spike on a viral capsid or viral envelope
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Classification
• Coronaviridae has two genera:
• Torovirus and Coronavirus
• Torovirus:
• The toroviruses are widespread in ungulates and appear to be
associated with diarrheas
• Coronavirus:
• The Coronaviridae family has been divided up into three groups,
originally on the basis of serological cross-reactivity, but more
recently on the basis of genomic sequence homology
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Classification
• Coronaviruses of domestic animals and rodents are included in two
groups
• There is a third distinct antigenic group which contains the avian
infectious bronchitis virus of chickens
• The novel coronavirus recovered in 2003 from patients with severe acute
respiratory syndrome (SARS) appears to represent a new (fourth)
group of viruses.
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Characteristics
• Coronaviruses are pleomorphic (Virions are spherical to
pleomorphic)
• Diameter 60-220 nm
• Enveloped, with spikes giving the virions the
appearance of a crown
• (+) single-stranded RNA genome
• Contain two major envelope proteins: matrix and spike
proteins
• Internal ribonucleoprotein (RNP) is helical
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Replication
• Entry into host cell cytoplasm, probably by viropexis
• Replication and particle assembly in cytoplasm
• Protein synthesis occurs in two phases on infection, the
genome is translated to produce a polyprotein that is cleaved
to produce an RNA-dependent RNA polymerase
• The polymerase generates a negative-sense template RNA
• RNA is used to replicate new genomes and produce five to
seven individual mRNAs for the individual viral proteins
• Progeny virions are released by budding from membranes of
rER and transported through vesicles
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Pathogenesis
• It is thought that 2–10 per cent of common colds are caused
by coronaviruses, typified by OC43 and 229E.
• Infection can precipitate wheezing in asthmatics and
aggravate chronic bronchitis in adults.
• In a typical case there is an incubation period of 3 days,
followed by an unpleasant nasal discharge and malaise,
lasting about a week.
• Patients excrete virus during this period.
• There is a little or no fever, and coughs and sore throat are
not common.
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Pathogenesis
• Replication is confined to the cells of the epithelium in the
upper respiratory tract.
• Infection remains localized to the upper respiratory tract
because the optimum temperature for viral growth is
33°C to 35°C.
• Less is known about the toroviruses.
• They are often visualized in diarrhoea samples and may
cause gastroenteritis.
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Epidemiology
• Coronavirus colds occur in the colder months of winter
and early spring with sizable outbreaks every 2-4 years.
• Most people have been infected in their lives
• Reinfections are quite common either because of the
poor immune response, or as a result of antigenic
mutations, or both.
• The virus is most likely spread by aerosols and in large
droplets (e.g., sneezes).
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Laboratory Diagnosis
• The trivial nature of the infection does not call for routine
diagnostic tests.
• For epidemiological purposes, paired acute and convalescent
sera can be tested by hemagglutination inhibition for a rising
titer of specific antibody.
• Virus isolation requires organ cultures of human embryo
trachea or nasal epithelium
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Treatment & Prevention
• Specific treatment
• There is no specific treatment for coronaviruses.
• Treatment is symptomatic and supportive.
• Prevention
• General hygiene and disinfection can prevent person-to person
spread.
• No vaccine is available.
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Severe Acute Respiratory Syndrome
(SARS CoV)
• The first cases of a new syndrome emerged in November
2002 in the Guangdong Province of China.
• By April 2003 the virus had spread worldwide
• Unexpectedly, the virus was identified as a coronavirus
(CoV), which emerged suddenly from a mammalian
reservoir in China to infect humans, probably the civet cat,
which is used for exotic foods, or a rat upon which the civet
preys.
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Global spread of
SARS.
Emergence of SARS
from a civet cat or rat.
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SARS CoV - Epidemiology
• Between November 2002 and July 2003, 8096 probable SARS cases
were reported to the World Health Organization.
• The total number of deaths rose to 774, with a case mortality rate of
9.6%. Since then, three laboratory-associated outbreaks occurred, with
a total of 11 cases.
• Since then SARS has not been circulating.
• SARS-CoV entered the human population from an animal source –
several animals have been found to have very closely related viruses.
• Spread of the virus was via respiratory droplets and, therefore, contact
with surfaces was important.
• Since it was excreted via the gastrointestinal tract, faecal–oral transfer
was a possibility.
• The incubation period was 4–6 (range 1–14) days and patients were
only infectious during the symptomatic period and most infectious
during the second week of illness.
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SARS CoV - Pathogenesis
• Determining the pathogenesis of SARS was difficult, based on autopsy
findings confused by the effects of treatment, e.g. ventilation and
medication.
• The virus replicates in the lower respiratory tract, followed by an innate
and a specific immune response, and both viral factors and immune
response (e.g. cytokine dysregulation) play a role in the pathogenesis.
• The first stage of the disease is associated with diffuse alveolar
damage, macrophage and T-cell infiltration, and type 2 pneumocyte
proliferation.
• The pulmonary infiltrate appears patchy on the chest X-ray.
• In the second stage, organisation occurs.
• The infection is not limited to the pulmonary system.
• The virus replicates in enterocytes, resulting in diarrhea, and is shed in
the stool, as well as urine, and possibly other body fluids.
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SARS CoV - Clinical picture
• The first phase of the disease consists of fever > 38°C with rigors,
myalgia, sore throat and gastrointestinal symptoms, with cough
and often shortness of breath beginning after about 3–7 days of
symptoms.
• Hypoxia may develop and 10–20% require ventilation.
• A relative lymphopenia and neutropenia may occur.
• Some patients showed a biphasic course, with apparent recovery
followed by worsening of the clinical condition.
• Mortality was highest in the elderly and lowest in the younger
population, and co-existing illness worsened morbidity and
mortality.
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SARS CoV – Laboratory Diagnosis
• Specimen:
• Nasopharyngeal swab or aspirate, throat swab or stool specimens
may be collected for laboratory diagnosis.
• Serum is used for antibody detection.
• Reverse transcription PCR—(RT-PCR)
• RT-PCR has been used for early diagnosis.
• Virus culture:
• Virus in clinical specimens can be cultured on Vero cell lines.
• Serology:
• Demonstration of rise in titer of antibodies by “ELISA or indirect
immunofluorescent test in paired serum samples are useful later.
• However, for early diagnosis PCR is preferred
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SARS CoV - Treatment
• Supportive treatment, such as ventilation, was the centerpiece of
the management of a SARS patient.
• Specific treatments, such as steroids, remain controversial
regarding their effect, whether adverse or beneficial, on SARS
patients.
• Ribavirin was used, as it is a broad-spectrum guanosine analogue,
and appeared to have some benefit,
• Other agents that have an effect on the inflammatory response,
such as chloroquine and interferon, and agents that interfere with
coronavirus protease activity, such as the lopinavir/ritonavir
combination.
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SARS CoV - Prevention
• Isolation of infected patients and quarantine of exposed
people, along with disinfection and infection control
precautions, were the key to prevention of spread.
• A vaccine has been investigated, but may be merely an
academic measure, relevant to future vaccine research, since
the epidemic is over and SARS is no longer circulating.
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PARAMYXOVIRIDAE
Introduction
• Family Paramyxoviridae causes a variety of diseases,
predominantly involving the respiratory tract, in humans, birds,
and other animals.
• In humans, they include:
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measles,
respiratory infections caused by respiratory syncytial virus (RSV)
and parainfluenza viruses,
and the more innocuous salivary gland infection of mumps.
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Characteristics
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Negative single-stranded RNA
Enveloped
150-200 nm in diameter
Helical nucleocapsid
Possess fusion protein which causes adjacent cells to fuse and
form multinucleate giant cells (syncytia)
Members of the genus Paramyxovirus possess neuraminidase
They possess matrix (M) protein
All possess hemagglutinin spikes with the exception of
respiratory syncytial virus
They have RNA reverse transcriptase
Virus replicates in the cytoplasm
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Replication
• Replication is of a
typical negativestranded RNA virus:
• Virus enters a cell by
fusion
• RNA transcriptase
synthesize (+) RNA
which then enters into
translation process
• The virus is released by
budding from the
plasma membrane
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Measles (Rubeola)
• A highly infectious disease
• Infection is acquired via droplets that enter the respiratory tract
• Pathogenies
• Incubation period: 10-14 days
• Replication in lymph nodes, then viremia follows
• Rash (due to reaction of cytotoxic T-cells with infected skin cells) first
appears on the face and spreads to the trunk and limbs (maculopapular)
• A maculopapular rash is a type of rash characterized by a flat, red area on
the skin that is covered with small confluent bumps.
• Koplik spots:
• Koplik spots are small, red, irregularly-shaped spots with blue-white centers
found on the mucosal surface of the oral cavity.
• Complications may include secondary bacterial infection and encephalitis
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maculopapular rash
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Measles - Laboratory Diagnosis
• Laboratory diagnosis is not needed since diagnosis is made on
clinical grounds
• Measles antigen can be detected in pharyngeal cells or urinary
sediment with immunofluorescence
• The measles genome can be identified by reverse transcriptase
polymerase chain reaction (RT-PCR) in either of the
aforementioned specimens
• Characteristic cytopathologic effects, including multinucleated
giant cells with cytoplasmic inclusion bodies, can be seen in
Giemsa stained cells taken from the upper respiratory tract and
urinary sediment
• Antibody, especially immunoglobulin M (IgM), can be detected
when the rash is present
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Measles - Prophylaxis
• Vaccination “live attenuated
measles virus, a component of
MMR” (measles, mumps and
rubella)
• Passive immunization using
human immunoglobulin for
immunocompromised children
Multinucleated giant cells
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Respiratory Syncytial Virus “RSV”
• Respiratory syncytial virus is distributed worldwide and is
recognized as the major pediatric respiratory tract pathogen.
• It is the most common cause of viral pneumonia in children
under age 5 years.
• RSV is highly contagious.
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RSV - Pathogenesis
• Infects the respiratory tract, does not spread
systemically
• In newborns, the infection may be fatal
because narrow airways are blocked by virusinduced pathology
• Infants are not protected from infection by
maternal antibody
• Reinfection may occur after a natural
infection
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RSV - Laboratory Diagnosis
• Isolation of the virus in continuous lines of human cells, e.g.,
HeLa, cytopathic effects with formation of syncytia appear
after 2-10 days.
• Immunofluorescence demonstrates viral antigen in cells
from nasal washing.
• Serological diagnosis is by demonstration of rising antibody
titers in paired serum samples.
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RSV - Prevention & Treatment
• Prevention
• Attempts to develop attenuated vaccines have so far met with little success;
the use of recombinant DNA technology for making RSV vaccine is now
being studied.
• In the absence of a vaccine, limitation of spread within paediatric units,
nurseries depends on good hygienic practice, such as hand washing,
covering of the mouth when coughing or sneezing, and careful disposal of
paper handkerchiefs.
• Treatment
• Small-scale trials of the nucleoside analogue ribavirin, given by continuous
aerosol inhalation to babies with serious RSV infections, met with some
success, but not enough to make it a routine treatment.
• High titer human immunoglobulin or humanized monoclonal antibodies are
efficacious in high-risk infants but the treatment is expensive and is used
only in emergencies
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Mumps
• Mumps virus is the cause of acute,
benign viral parotitis (painful
swelling of the salivary glands).
• Mumps is rarely seen in countries
that promote use of the live vaccine,
which is administered with the
measles and rubella live vaccines.
• The virus is most closely related to
parainfluenza virus 2, but there is no
cross-immunity with the
parainfluenza viruses.
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Mumps
• The infection is acquired by the respiratory route.
• Viremia is followed by generalized spread to various organs, including the
parotid gland.
• Complications
• Orchitis
• Meningitis
• Control
• Vaccination (component of MMR)
• There is only one antigenic type of mumps virus, and it does not exhibit
significant antigenic variation. Immunity is permanent after a single infection.
• Laboratory studies are not usually required to establish the diagnosis of typical
cases.
• The diagnosis may be established by virus isolation and serological tests
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Parainfluenza Viruses
• Parainfluenza viruses, which were discovered in the late 1950s, are
respiratory viruses that usually cause mild coldlike symptoms but can
also cause serious respiratory tract disease.
• Four serologic types within the parainfluenza genus are human
pathogens.
• Types 1, 2, and 3 are second only to RSV as important causes of
severe lower respiratory tract infection in infants and young children.
• They are especially associated with laryngotracheobronchitis (croup).
• It involves the respiratory system and also includes the larynx or the vocal
cords, the trachea, and bronchial tubes which forms the upper airways of the
lungs.
• Type 4 causes only mild upper respiratory tract infection in children and
adults.
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Parainfluenza Viruses
• Unlike measles and mumps viruses,
the parainfluenza viruses rarely cause
viremia.
• The viruses generally stay in the
upper respiratory tract, causing only
cold-like symptoms.
• In approximately 25% of cases, the
virus spreads to the lower
respiratory tract, and in 2% to 3%,
disease may take the severe form of
laryngotracheobronchitis.
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Parainfluenza Viruses
• laboratory diagnosis
• Immunofluorescence or ELISA to detect Ag
• Virus Isolation
• Serology: Serodiagnosis should be based on paired sera
• Vaccination with killed vaccines is ineffective, possibly because
they fail to induce local secretory antibody and appropriate
cellular immunity.
• No live attenuated vaccine is available.
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Nipah and Hendra Viruses
• A new paramyxovirus, Nipah virus, was isolated from patients after an
outbreak of severe encephalitis in Malaysia and Singapore in 1998.
• Nipah virus is more closely related to the Hendra virus, discovered in
1994 in Australia, than to other paramyxoviruses.
• Both viruses have broad host ranges, including pigs, man, dogs, horses,
cats, and other mammals. For Nipah virus, the reservoir
is a fruit bat (flying fox).
• The virus can be obtained from fruit contaminated by infected bats or
amplified in pigs and then spread to humans.
• The human is an accidental host for these viruses, but the outcome of
human infection is severe.
• Disease signs include flulike symptoms, seizures, and coma.
• Of the 269 cases occurring in 1999, 108 were fatal.
• Another epidemic in Bangladesh in 2004 had a higher mortality rate.
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