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Categories of Respiratory Viruses
• Orthomyxoviridae: Influenza virus
• Paramyxoviridae : Parainfluenza virus; Mumps virus; Measles; Respiratory
syneytical virus
• Togaviridae: Rubella Virus
• Coronaviridae: Corona Virus; SARS virus • Adenoviridae : human Adenovirus
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Influenza virus
Orthomyxoviridae: Influenza virus Influenza is a disease caused by
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Genome
of Influenza virus
• 8 negative sense RNA nucleocapsid segments
• The 'RNP' (RNA + nucleoprotein) is in a helical form with the 3 polymerase
polypeptides associated with each segment.
• The segmented genome promotes genetic diversity caused by mutation and
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Virion
• spherical/ovoid, 80-120nm diameter,
• The inner side of the envelope is
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Virion
• The outer surface of the particle consists of a lipid envelope from which project
prominent glycoprotein spikes of two
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Haemagglutinin (HA)
• Encoded by RNA segment #4
• Can agglutinate red blood cells - hence the nomenclature
• Cleavage by host-cell protease is required (resulting in HA1 and HA2) for infection to occur
• Hemagglutinin glycoprotein is the viral
attachment protein and fusion protein , and it elicits neutralizing , protective antibody
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Neuraminadase (NA)
• Encoded by RNA segment #6
• Enzyme that uses neuraminic (sialic) acid as a substrate
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ORTHOMYXOVIRUSES
M1 protein
helical nucleocapsid (RNA plus NP protein)
HA - hemagglutinin
polymerase complex
lipid bilayer membrane
NA - neuraminidase
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Replication
• Influenza transcribe and replicates its genome in the target cell nucleus
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Antigen
• Soluble antigens: include ribonucleoprotein and
M protein which are much stable in antigenicity.
• Surface antigens: include HA and NA which are
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Types
• Influenza viruses are divided into 3 groups determined by the ribonucleoprotein (RNP) antigen and M antigen:
• Group A - This group is the cause of
epidemics and pandemics and has an avian intermediate host (IH)
Group B - This group causes epidemics and has no IH
15 TYPE A ++++ yes yes yes shift, drift yes sensitive sensitive 2
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Subtypes
• According to antigenicity of HA and NA,
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Variation and Epidemiology
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Antigenic Shift Of
Influenza virus
• Reassortment of genes is a common
feature of Influenza A, but not B or C
• When two different "A" viruses infect the same cell, their RNA segments can
become mixed during replication
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Antigenic Drift of Influenza
Virus
•Constant mutations in the RNA of influenza which lead to polypeptide mutations
•Changes are less dramatic than those induced by Shift
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where do “new” HA and NA come
from?
• 13 types HA • 9 types NA
– all circulate in birds
• pigs
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why do we not have influenza B
pandemics?
• so far no shifts have been
recorded • no animal
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Resistence
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Pathogenesis
• Influenza is characterised by fever, myalgia, headache and pharyngitis. In addition there may be cough and in severe cases,
prostration. There is usually not coryza 鼻炎
(runny nose) which characterises common cold infections.
• Infection may be very mild, even
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Transmission
• Source of infection: patients and carriers.
• AEROSOL
– 100,000 TO 1,000,000 VIRIONS PER DROPLET
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NORMAL TRACHEAL MUCOSA
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SYMPTOMS
• FEVER
• HEADACHE
• MYALGIA( 肌痛 ) • COUGH
• RHINITIS( 鼻炎 )
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PULMONARY COMPLICATIONS
• CROUP (YOUNG CHILDREN)
• PRIMARY INFLUENZA VIRUS PNEUMONIA • SECONDARY BACTERIAL INFECTION
– Streptococcus pneumoniae – Staphlyococcus aureus
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NON-PULMONARY COMPLICATIONS
• myositis (rare, > in children, > with type B)
• cardiac complications • liver and CNS
– Reye’s syndrome
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Lab Diagnosis
• Viral detection:
Respiratory secretions
( direct aspirate , gargle , nasal washings ) 1. Cell culture in primary monkey kidney or
madindarby canine kidney cells 2. Hemagglutination (inhibition) Hemadsorption (inhibition)
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• Serology
hemagglutination inhibition Hemadsorption inhibition ELISA
immunofluoresence complement fixation.
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Prevention
• Vaccines at best give about 70% protection. They may sometimes not be effective against the most recently evolved strains because the rate of evolution outpaces the rate at which
new vaccines can be manufactured.
• This constant antigenic change down the
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Types of Vaccine
• Killed Whole Virus
Rather pyrogenic, not used today.
• Live Virus
Attenuated strains were widely used in Russia but not elsewhere.
• Virus Subunit
HA extracted from recombinant virus forms the basis of today's vaccines.
For example, the WHO Recommendation for Influenza Vaccine, 1995-1996, contains two A strains and one B strain:-[A / Singapore / 6 / 86 (H1N1)+A / Johannesburg / 33 / 94 (H3N2) +B / Beijing / 84 / 93 ]
• Synthetic
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40 PB2 PB1 PA HA NA NP M NS PB2 PB1 PA HA NA NP M NS PB2 PB1 PA HA NA NP M NS Attenuated Donor Master Strain New Virulent Antigenic Variant Strain
X
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Treatment
• Amantadine and rimantadine are active against influenza A viruses. The action of these closely related agents is
complex and incompletely understood, but they are believed to block cellular membrane ion channels, and inhibit an uncoating step and target the M2
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PREVENTION - DRUGS
• RIMANTADINE 金刚乙胺 (M2)
• type A only
• AMANTADINE 金刚烷胺 (M2)
• type A only
• ZANAMIVIR (NA)
• types A and B, not yet approved for prevention but studies show effective
• OSELTAMIVIR (NA)
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TREATMENT - DRUGS
• RIMANTADINE (M2)
• type A only, needs to be given early
• AMANTADINE (M2)
• type A only, needs to be given early
• ZANAMIVIR (NA)
• types A and B, needs to be given early
• OSELTAMIVIR (NA)
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OTHER TREATMENT
• REST, LIQUIDS, ANTI-FEBRILE AGENTS
(NO ASPIRIN FOR AGES 6MTHS-18YRS)
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Paramyxoviridae
• Genus Human pathogen
• Morbillivirus Measles virus
• Paramyxovirus Parainfluenza viruses,
Mumps virus
• Pneumovirus Respirtory syncytical
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Virion
Virion
• Large virion consists of a negative RNA
genome in a helical nucleocapsid surrounded by an enevlope containing a viral attachment protein
• HN of paramyxovirus and mumps virus has hemagglutinin and neuraminidase.
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M protein
helical nucleocapsid (RNA plus NP protein)
HN/H/G glycoprotein SPIKES
polymerase complex
lipid bilayer membrane
F glycoprotein SPIKES
PARAMYXOVIRUSES
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PARAMYXOVIRUS FAMILY
properties of attachment protein
GENUS GLYCOPROTEINS TYPICAL MEMBERS
Paramyxovirus
genus HN, F HPIV1, HPIV3 Rubulavirus
Genus HN, F HPIV2, HPIV4 mumps virus
Morbillivirus
genus H, F measles virus Pneumovirus
genus G, F
respiratory
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Replication , Pathogenesis and Immunity
• Virus replicates in the cytoplasm
• Virions penetrate the cell by fusion with the plasma membrane
• Viruses induce cell-cell fusion, causing multinucleated giant cells
• Paramyxoviridae are transmitted in respiratory
droplets and initiate infection in the respiratory tract • Cell-mediated immunity causes many of the
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MMR vaccine
• Composition : live attenuated virus Measles / Mumps / Rubella
• Vaccination schedule: at 15-24 months and at 4 to 6 years or before junior high school • Efficiency: 95% lifelong immunization with a
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Pathogenesis and Immunity
• Childhood infection almost universal, protection resulting from this is probably lifelong. Both man and wild monkeys are commonly infected
• In culture, produces characteristic intranuclear inclusion bodies and syncytial giant cells.
• Transmission and initial stages of disease similar to mumps, but this virus can also infect via the eye
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Pathogenesis and Immunity
• After a 10-12 day incubation period
• Dry cough, sore throat, conjunctivitis (virus may be excreted during this phase!), followed a few days later by the characteristic red, maculopapular rash and Koplik's spots
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DISSEMINATED SPREAD
• LONGER TIME FOR SYMPTOMS
• IMMUNE RESPONSE • IF SYMPTOMS DUE
TO IMMUNE
RESPONSE, USUALLY INFECTIOUS PRIOR TO SYMPTOMS
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MEASLES - Koplik’s spots
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MEASLES - RASH
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DISEASE
• FEVER
• RESPIRATORY TRACT SYMPTOMS • rhinorrhea, cough
• KOPLIK’S SPOTS
• MACULOPAPULAR RASH • T-cells ->endothelial cells
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MEASLES GIANT CELL PNEUMONIA
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MEASLES ENCEPHALITIS
• 1/1000 cases • sequelae
– deafness – seizures
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SSPE
• sub-acute sclerosing panencephalitis
– inflammatory disease – defective virus
• early infection with measles is a risk factor • rare (7/1,000,000 cases of measles)
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Treatment
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Prevention
• Both live and killed vaccines exist.
Vaccination with the live attenuated vaccine has been practised since the 1960's with a dramatic decline in the incidence of the
disease .
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Mumps virus
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Mumps virus
• Droplets spread the infection via saliva and secretions from the respiratory
tract.
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Mumps virus
• Malaise and fever is followed within a day by
painful enlargement of one or both of the parotid (salivary) glands
• A possible complication in males after puberty is
orchitis - painful swelling of one or both testicles. • Inflammation of the ovary and pancreas can also
occur.
• Disease is usually self-limiting within a few days • Aseptic meningitis (usually resolving without
problems) or postexposure encephalitis (can prove fatal) are the most serious complications
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Prevention and treatment
• Treatment: none (passive immunization has been used).
• Prevention: one invariant serotype therefore vaccines are viable - both
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MUMPS
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Parainfluenza virus
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Important Characteristics
• Typing: Four types (1-4) : distinguished antigenically, by cytopathic effect, and pathogenically
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Pathogenesis and Immunity
• Cause acute respiratory infections of
man ranging from relatively mild
influenza-like illness to bronchitis, croup
(narrowing of airways which can result
in respiratory distress) and pneumonia;
common infection of children.
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Lab Diagnosis
• Nasopharynx specimen is culture in a
surrogate cell line in AGMK. Infected cell are detected by hemeadsorption or DFA
• DFA also can be done rapidly to identify the agent in direct specimen
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Treatment
• No antiviral therapy is available
• Nursing the patient in a humidified atmosphere was commonly advised
• Dexamethasone 地塞米松 and budesonide
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Prevention
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Important Characteristics
• RSV is highly infectious, transmission by respiratory secretions.
• Primary multiplication occurs in epithelial cells of
URT producing a mild illness. In ~50% children less than 8 months old, virus subsequently spreads into the L.R.T. causing bronchitis, pneumonia and croup. • Has been suggested as a possible factor in cot
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Pathogenesis and immunity
Disorder Age
Bronchiolitis Fever, cough, dyspnea, and pneumonia, cyanosis in children younger or both than 1 year
Febrile rhinitis Children and pharyngitis
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Lab Diagnosis
• DFA
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Treatment
• Ribavirin aerosol( 三 ( 氮 ) 唑核苷 , 病毒唑 ) is recommended for pneumonia in infants
• RSV - IGIV has been approved for infants born prematurely
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Prevention
• Currently no effective vaccine! Also, infection does not result in lasting protection (c.f.
mumps, measles) therefore repeated
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Adenoviruses
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General Concepts
• Most Adenovirus infections involve either the respiratory or gastrointestinal tracts or the
eye.
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Important
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Pathogenesis and Immunity
• Disease: At Risk:
• Acute Respiratory Illness Military recruits, boarding schools,
• Pharyngitis Infants
• Gastroenteritis Infants • Conjunctivitis All
• Pneumonia Infants, military recruits • Keratoconjunctivitis All
• Acute Haemorrhagic Cystitis Infants
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swimming pool conjunctivitis
( 游泳池结膜炎
;
红眼病 )
• Eye infections characterized by a mild conjunctivitis "swimming pool
conjunctivitis" are caused by
adenoviruses and have been linked to transmission in contaminated
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Lab Diagnosis
• Isolation of adenovirus can be accomplished in cell cultures derived from epithelial cells
• Immunoassays, including fluorescent antibody and enzyme-linked immunosorbent assays,
PCR can be used to detect and type the virus in clinical samples and tissue cultures
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Treatment
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Prevention
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Rubella Virus
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General Concepts
• Viruses have enveloped single stranded positive-sense RNA.
• Replication in cytoplasm and bud at plasma membrane
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Epidemiology
• Occurrence: worldwide in prevalence( in winter and spring)
• Reservoir: Humans
• Mode of Transmission: Vertical transmission in case of CRS/ Infection in nonimmune
children is usually transmitted by droplet spread or by direct contact with patients
• Who is at risk: Non-immunized children are at risk
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Pathogenesis
Rubella enters and infects the nasopharynx and lung and then spreads to the lymph nodes and reticuloendothelial system. The
resulting viremia spreads the virus to other tissues and the skin.
Circulating antibody can block the transfer of virus at the indicated points. In an immunologically deficient pregnant woman, the virus can infect the placenta and spread to the fetus
Virus
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EFFECTS ON FETUS
• HEARING LOSS
• CONGENITAL HEART DEFECTS • NEUROLOGICAL
– PYSCHOMOTOR AND/OR MENTAL RETARDATION
• OPHTHALMIC
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EFFECTS ON FETUS
• thrombocytopenia • hepatomegaly
• splenomegaly
• intrauterine growth retardation • bone lesions
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EFFECTS ON FETUS
• First trimester
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EFFECTS ON FETUS
• 1964
– 20,000 infants with permanent problems – 6,000 to 30,000 spontaneous abortions – 5,000 therapeutic abortions
• 1969 to present
– maximum of 67 cases congential rubella/yr
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CONGENITAL INFECTIONS
• SHED VIRUS FOR A YEAR OR MORE AFTER BIRTH
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CONGENITAL INFECTIONS
• EYE PROBLEMS
• GLANDULAR COMPLICATIONS
– diabetes,
– thyroid problems
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CONGENITAL / VERY EARLY
INFECTIONS
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Lab Diagnosis
• Current rubella infection, in pregnant women can be confirmed by 4-fold rise in specific
antibody titer between acute and
convalescent-phase serum specimens by
ELISA
• The Dx of CRS in the newborn may be
confirmed by the presence of specific IgM
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Treatment
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Prevention
• A single dose of live, attenuated rubella vaccine elicits a significant antibody
response in approximately 98%-99% of vaccinated individuals
• It should not be given to
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Coronavirus
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Important Characteristics
• Virion: Spherical, 80-160nm in diameter, helical nucleocapside
• Genome: +ssRNA, linear, nonsegmented, 27-30kb, infectious
• Proteome: two glycoproteins and one
phosphoprotein. Some viruses contain a third glycoprotein (hemagglutinin esterase)
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Virion structure
• S-Spike
glycoprotein:
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Pathogenesis and Immunity
• These viruses infect a variety of mammals & birds. The exact number of human isolates are not known as many cannot be grown in culture.
• They cause: common colds and have been implicated in gastroenteritis in infants.
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Rhinovirus
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Important Characteristics
• Rhinoviruses are picornaviruses similar to
enteroviruses but differ from them in having a buoyant density in cesium chloride of 1.40
g/ml and in being Acid-labile
• Rhinoviruses are isolated commonly from
the nose and throat but very rarely from feces.
• These viruses cause upper respiratory
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Reovirus
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Important Characteristics
• Virion: Icosahedal, 60-80nm in diameter, double capsid shell
• Genome: dsRNA • Envelope: none
