paramyxoviruses 미생물학교실 권 형 주. genushuman pathogen mobillivirus measles virus...

Paramyxoviruses

미생물학교실

권 형 주

Genus Human Pathogen

Mobillivirus Measles virus (rubeola, 홍역 – maculopapular rash)

ParamyxovirusParainfluenza viruses 1 to 4

Mumps virus

PneumovirusRespiratory syncytial virus –upper respiratory tract infection

Metapneumovirus

- Cell-cell fusion•Syncytia formation•Multinucleated giant cells

- New group• Zoonosis-causing viruses• Nipah virus• Hendra virus

- Live vaccine•Measles viruses•Mumps viruses• only one serotype

Paramyxoviruses (from Greek para-, beyond, -myxo-, mucus or slime, plus virus, from Latin poison, slime)

STRUCTURE and REPLICATION- Negative-sense, single-stranded RNA- Envelope-the order of the protein-coding regions differs for each genus- orthomyxoviruses : segmented genome

Replication of paramyxoviruses

Measles Virus ( 홍역바이러스 )- Measles is still one of the most prominent causes of disease (45 million cases per year) and death (1 to 2 million per year) worldwide in unvaccinated populations

Pathogenesis and Immunity

Family : Paramyxoviridae

Genus : Mobillivirus

- Host – only human- cell fusion, giant cells- cell-to-cell spread escape antibody control- Hemagglutinin(+), Neuraminidase (-)- Highly contagious- respiratory droplets

- Time course of measles virus infection.- 초기증상 : cough, conjunctivitis, coryza, and photophobia (CCC and P)- Koplik’s spots, rash- SSPE (subacute sclerosing panencephalitis, 아급성경화범뇌염 )-rare

- Maculopapular measles rash : T cells targeted to measles-infected endothelial cells lining small blood vessels rash (lifelong immunity)

- Encephalitis 1) direct infection of neurons 2) a postinfectious encephalitis :

immune mediated 3) SSPE – a defective variant of

measles

Epidemiology- Development of effective vaccine

programs

Clinical Syndromes- Incubation periods : 7-13 days- 초기증상 ( 발진전 ) : High fever, CCC and p- After 2 days of illness : Koplik spots - A typical mucous membrane lesions - first day or two after the rash appears - mouth, conjunctivae, vagina- 발진 (exanthem of measles) : starts belows the ears and spreads over

the body : maculopapular rash- Complications : Pneumonia, bacterial

superinfection

Prevention

Parainfluenza Virus- Respiratory viruses : mild cold-like symptoms, serious respiratory

tract disease- Human pathogens : four serotypes

Clinical Syndromes- Types 1, 2, 3 : respiratory tract syndromes - mild cold-like upper respiratory tract infection (coryza,

pharyngitis, mild bronchitis, wheezing, fever) - Bronchiolitis - Pneumonia - Croup (laryngotracheobronchitis)

Laboratory Diagnosis- Isolated from nasal washing and respiratory

secretion- Grow well in primary monkey kidney cells- Hemagglutination- Serotype (antibody) ; hemagglutination inhibition- RT-PCR

- Administration of nebulized cold or hot steam- No specific antiviral agents- Killed vaccine : ineffective- No live attenuated vaccine

Treatment, Prevention, and Control

Mumps Virus- 볼거리 , 볼치기 ( 귀밑샘염 )- Parotitis ( 이하선염 ) : painful swelling of the salivary

glands- Isolated in embryonated eggs in 1945- Cell culture in 1955- Human pathogen : One serotype

- Recovered from saliva, urine, pharynx, stensen duct, cerebrospinal fluid

- Grow well in monkey kidney cells- Formation of multinucleated giant cells- Hemadsorption of guinea pig

erythrocytes: hemagglutinin- MMR vaccine- Antiviral agents are not available

Respiratory Syncytial Virus (RSV)호흡기세포융합바이러스

Family : ParamyxoviridaeGenus : PneumovirusSubgroups : A and B- Fatal acute respiratory tract

infection- Infants, young children

RSV Virion, Genome and Proteins

plasmamembrane

budding virion

(EM by Tony Kalica, LID/NIAID)150 nm

NS2NS1

M2-1

M2-2

Single-stranded negative-sense RNA, 15.2 kb

3´ 5´ G FSHMN P L

ribonucleocapsid

envelope spikes

nonstructural

NS1NS2

inhibit host type I interferon response

regulation of RNA synthesis

M2-2

unassigned

inner envelope face

assemblyM

M2-1

transcription processivity factor

RNA-binding

phosphoprotein

polymerase

N

PL

Neutralizationtargets

SH

G attachment

fusion

unknownF

RSV –syncytium formation

- Virus infections almost always occur in the winter. - Infants : lower respiratory infection (bronchiolitis and pneumonia) - Children : mild to pneumonia - Adults : mild symptoms

• Symptom : bronchiolitis, pneumonia, mechanical ventilation, and respiratory failure in infants.

Laboratory Diagnosis

Treatment, Prevention, and Control

- RT-PCR- Immunofluorescence and enzyme immunoassay test

- Ribavirin ( 제한적 ) : inhalation(nebulization)- Passive immunization :anti-RSV Ig ( 제한적 )- No vaccine is currently available- Inactivated vaccine : severe RSV disease : heightened immunologic response (Th2 immune

response ?)