RESPIRATORY VIRUSES

Including…

• Orthomyxoviridae( 正粘病毒科 ) : Influenza virus• Paramyxoviridae( 副粘病毒科 ): Respiratory syncytial virus(RSV),measles virus, m

umps virus.• Other viruses rhinovirus,adenovirus,coronavirus…

INFLUENZA VIRUS• RNA virus, genome consists of 8 seg

ments• enveloped virus, with haemagglutinin

and neuraminidase spikes• 3 types: A, B, and C• Type A undergoes antigenic shift and

drift.• Type B undergoes antigenic drift onl

y and type C is relatively stable

Biological Properties

Segment Protein Function

1 PB2 Polymerase component

2 PB1 Polymerase component

3 PA Polymerase component

4 HA Hemagglutinin, viral attachment protein, fusion protein, target of neutralizing antibody

5 NP Nucleocapsid

6 NA Neuraminidase (cleaves sialic acid and promotes virus release)

7 M1 Matrix protein:Viral structural protein (interacts with nucleocapsid and envelope, promotes assembly)

M2 Membrane protein (forms membrane channel and target for amantadine facilitates uncoating and HA production)

8 NS1 Nonstructural protein (inhibits cellular mRNA translation)

NS2 Nonstructural protein (important but unknown function)

Structure and Composition

HA

NA

PB2PB1PA

NP

RNA

Antigen Soluble antigens: include ribonucleoprotein and M p

rotein which are much stable in antigenicity. 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• Group C - This group does not cause epidemics and causes mild disease• Surface antigens: include HA and NA which are mu

ch variable in antigenicity. According to antigenicity of HA and NA, influenza

virus is divided into subtypes such as HnNm( H1N2, et al )

TYPE A

++++yesyesyesshift, driftyessensitivesensitive2

severity of illnessanimal reservoirhuman pandemicshuman epidemicsantigenic changessegmented genomeamantadine, rimantidinezanamivirsurface glycoproteins

TYPE B

++nonoyesdriftyesno effectsensitive2

TYPE C

+nonono (sporadic)driftyesno effect

(1)

Epidemic

Pathogenesis and Immunity

• Influenza virus spread rapid via aerial droplets and fomites with inhalation into the pharynx or lower respiratory tract.

• fever, myalgia, headache, pharyngitis, cough and prostration

• cell-mediated immune response is important, IgG and IgA are important in protection against reinfection

where do “new” HA and NA come from?

why do we not have influenza B pandemics?

• so far no shifts have been recorded

• no animal reservoir known

Laboratory Diagnosis • Detection of Antigen - a hemagglutination inhibition

serologic test and ELISA.

• Virus Isolation - virus may be readily isolated from nasopharyngeal aspirates and throat swabs. The virus is generally isolated in primary monkey kidney cell cultures, the Madin-Darby canine kidney cell line, or embryonated eggs.

• Identify the influenza genome - RT-PCR

Treatment and Prevention

• prevented by active immunization with a polyvalent killed or subunit vaccine

• Amantadine, Zanamivir and oseltamivir

PARAMYXOVIRUSES • Paramyxoviruses are spherical,

enveloped viruses with a single helical nucleocapsid containing single-stranded, negative-sense RNA.

• a fusion (F) protein and a viral attachment protein (hemagglutinin-neuraminidase [HN], hemagglutinin [H], or G protein).

Important properties of paramyxoviruses.

• Virion: Spherical, pleomorphic, 150 nm or more in diameter (helical nucleocapsid, 13–18 nm)

• Composition: RNA (1%), protein (73%), lipid (20%),carbohydrate (6%)

• Genome: Single-stranded RNA, linear, nonsegmented, negative-sense, noninfectious, about 15 kb

• Proteins: Six to eight structural proteins• Envelope: Contains viral hemagglutinin (HN) glycoprotei

n (which sometimes carries neuraminidase activity) and fusion (F) glycoprotein; very fragile

• Replication: Cytoplasm; particles bud from plasma membrane

• Outstanding characteristics: Antigenically stable/ Particles are labile yet highly infectious

Characteristics of genera in the subfamilies of the family Paramyxoviridae.

Measles virus

• Highly contagious, only one serotype and infects only humans

• The prodrome starts with high fever, cough, coryza, conjunctivitis and photophobia

• Typical mucous membrane lesions-Koplik's spots

• Exanthema of measles spreads over the body

54

MEASLES - Koplik’s spots

Murray et al. Medical Microbiology

56

MEASLES - RASH

CDC - B.Rice Murray et al. Medical Microbiology

56

DISEASE• FEVER• RESPIRATORY TRACT SYMPTOMS

• rhinorrhea, cough

• KOPLIK’S SPOTS• MACULOPAPULAR RASH

• T-cells ->endothelial cells

• CONJUNCTIVITIS• epithelial cells

56

MEASLES GIANT CELL PNEUMONIA

Murray et al. Medical Microbiology

Measles virus• complication : pneumonia, encephalomyelitis, Subacute

sclerosing panencephalitis (SSPE)

• prevented by a live attenuated measles vaccine to children; immune globulin to exposed susceptible people

Natural history of measles

Mumps virus（腮腺炎病毒）

Mumps virus

• cause of acute, benign viral parotitis 耳下腺炎 - a very communicable disease with only one serotype, and it infects only humans.

• spread by direct person-to-person • incubation period may range from 7 days to 25 days but is

typically about 18 days • may affect the testes and ovaries, causing swelling and

pain especially after puberty. Orchitis can result in sterility. • immunity is permanent • prevented by a live attenuated vaccine (MMR)

Mims et al., Medical Microbiology 1993

Parainfluenza virus • Types 1, 2, and 3 cause of severe lower respiratory t

ract infection in infants and young children. Type 4 causes only mild upper respiratory tract infection in children and adults

• transmitted by person-to-person

• Primary infections usually occur in infants and children younger than 5 years

• reinfections occur throughout life, indicating that immunity is short-lived

Respiratory syncytial virus (RSV)

• no haemagglutinin or neuraminidase or hemolytic properties

• induces many large syncytia with cytoplasmic inclusions

• cause any respiratory tract illness, from a common cold to pneumonia

• pathologic effect-due to direct viral invasion of the respiratory epithelium, which is followed by immunologically mediated cell injury.

• No vaccine is currently available for RSV prophylaxis.

Human metapneumovirus

• Newly isolation: 2001.• Respiratory infections.• Failed to grow on cell culture.• RT-PCR

Nipah virus & Hendra virus

• Genus:Henipavirus 2002• Isolation:1999. zoonotic virus.• 120-500nm,not segmented,6 structural genes.• Natural host: 马来大狐蝠• It has caused disease in animals and in humans, through

contact with infectious animals. • Fever ， headache ， encephalitis…• High mortality rate.

RUBELLA VIRUS • a member of the Togaviridae family • It cause German measles, a systemic infection characterized by

lymphadenopathy and morbilliform rash • transmitted via respiratory droplets and from mother to fetus

transplacentally • congenital rubella syndrome (CRS), cataracts, heart defects, sensorine

ural deafness, mental retardation• lifelong immunity • No treatment has been found for rubella • The best means of preventing rubella is vaccination with the live

attenuated vaccine

Natural history of primary rubella infection:virus production and antibody responses.

Adenovirus

ADENOVIRUS

• 100 serotypes, at least 51 of which infect humans, classified into six species

• nonenveloped with an icosahedral nucleocapsid comprises 240 capsomeres, which consist of hexons and pentons

• spread by droplet, fomites and ingestion • causing lytic (e.g. muco-epithelial cells), latent (e.g. lymph

oid and adenoid cells), and transforming (hamster, not human)

• respiratory tract infection, conjunctivitis (pink eye), hemorrhagic cystitis, and gastroenteritis

Disease At RiskAcute Respiratory Illness Military recruits, boarding schools,

Pharyngitis Infants

Gastroenteritis Infants

Conjunctivitis All

Pneumonia Infants, military recruits

Keratoconjunctivitis All

Acute Haemorrhagic Cystitis Infants

Hepatitis Infants, liver transplant

swimming pool conjunctivitis

CORONAVIRUS • Enveloped, pleomorphic morphology• 2 serogroups: OC43 and 229E• In March 2003, a novel coronavirus (SAR

S-CoV) was discovered in association with the outbreak of severe acute respiratory syndrome (SARS)

• SARS is a form of atypical pnermonia characterized by high fever (>38C), chills, rigors, headache, dizziness, malaise, and myalgia, cough or breathing difficulty, and a history of exposure to a person or place associated with SARS within the previous 10 days

RHINOVIRUS

• belonging to the family Picornaviridae, more than 100 serotypes

• cause of the common cold and upper respiratory tract infections

• infections are self-limited and do not cause serious disease

• transmitted by two mechanisms, as aerosols and on fomites (e.g. by hands or on contaminated inanimate objects