ORTHOMYXOVIRU

S
PARAMYXOVIRUS
Husni Samadin
Lab. Mikrobiologi FK.Unsri/RSMH

Orthomyxovirus
Influenza virus
Influenza A- pandemics and epidemics;
humans and animals
Influenza B- epidemics; human virus
Influenza C- mild respiratory tract infection

 Morphology:
Segmented, ss genome,helical nucleocapsid
with outer lipoprotein envelope
Envelope contain 2 spikes
Hemagglutinin
Binds to cell surface receptors( neuraminic acid/sialic
acid

Neuramidase
Enzymatic activity

Internal antigens- M1 & NP proteins- type

specific, shows cross reactivity

Structure and Replication

The virus envelope contains two glycoproteins:
1. Hemagglutinin (HA)
2. Neuraminidase (NA)
3. Its lined by the matrix (M1) and membrane (M2) p

influenza A and B viral genomes consists of eight

different helical nucleocapsid segments.
Each segment contains a negative-sense RNA associated
with the nucleoprotein (NP) and the transcriptase (RNA
polymerase)
All virus proteins are encoded on separate segments,
except NS1, NS2, M1,
M1 and M2 proteins, which are
transcribed from one segment each.

Antigenic Shift and drift phenomenon of influenza

v.:
The HA has several functions:
1.
2.
3.
4.

attachment protein, bind to sialic a. cell receptors

promotes fusion of envelope to cell membrane
hemagglutinates human RBCs
it elicits the protective neutralizing antibody response.
response

HA & NA of ONLY influenza A virus can undergo

major antigenic changes (called: shifts,
shifts due to RNA
segment reassortment)
reassortment
Minor changes (called: drift, due to gene mutation)
mutation
occurs in both influenza A & B types.

 Antigenic Variations
Antigenic shift
Undergoes reassortment
Results in changes of the H and N antigen
Pandemics and epidemics
Occurs with influenza A only

Antigenic drift
Change in the amino acid sequence of the H ag
Occur both in A & B

Influenza Viral replication

Pathogenesis of Influenza virus infection

Influenza virus first targets and kills mucus-secreting,
ciliated, and other epithelial cells, causing the loss of this
primary innate defense mechanisms.
NA facilitates the development of the infection by
cleaving sialic acid residues of the mucus.
Virus copies are released at the apical surface of cells
(due to insertion of the HA in those sites)..
This leads to cell-to-cell spread and transmission to
LRT.
In LRT, viral infection can cause severe desquamation
of bronchial or alveolar epithelium down to a single-cell
basal layer or to BM.

As you know, influenza virus is released after ~ 8 h.

The infection promotes bacterial adhesion to epithelial
cells. Pneumonia may result from a viral pathogenesis or
from a secondary bacterial infection.
Influenza may also cause a transient or low-level
viremia but rarely involves tissues other than the lung.
Interferon and cytokine responses are concomitant
with the febrile phase of disease.
T-cell responses are important for effective recovery
and immunopathogenesis.
However, influenza infection depresses macrophage
and T-cell function, hindering immune resolution.
Interestingly, recovery often precedes detection of
antibody in serum or secretions !!

 MOT: airborne respiratory droplets ( less than

10 um)

Survive for short period on surfaces

I.P. 18-72 hours
Virus concentration in nasal and tracheal secretions
remains high for 24 to 48 hours

Site of infection- epithelial cells of the

respiratory tract
Humoral Immunity- ( IgG & IgA)protection
against reinfection, antibody against HA is
important

Symptoms and
complications
1. Uncomplicated influenza

Fever ( 38-40 C)
Myalgias, headache
Ocular symptoms- photophobia, tears, ache
Dry cough, nasal d/c

2. Pulmonary complications/sequelae

Croup( acute larygotracheobronchitis)

Primary influenza pneumonia
Secondary bacterial infection

 3. Non pulmonary complications

Myositis
Cardiac complications
Encephalopathy
Reyes syndrome
Guillen-Barre syndrome

Diagnosis
1. virus isolation

Monkey kidney cell etc.

No CPE

2.serology
Hemadsorption
PCR

Chemotherapy

Rimantadine and amantadine

Zanamavir and oseltamivir
Rest, liquids and anti febrile agents

Epidemiologic Concerns
Strains of influenza A virus are classified by the following
four characteristics:
Type (A, B, and C)
Place of original isolation
Date of original isolation
Antigen (HA and NA)
For example, a strain might be designated:
A/Bangkok/1/79 (H3N2)
This means that it is an influenza A virus that was first
isolated in Bangkok in January 1979 and contains HA (H3)
and NA (N2) antigens.
For Influenza B virus: same but antigen is not
mentioned..why ?

Influenza is spread via airborne droplets expelled during

talking, breathing, and coughing.
Influenza virus can survive on surfaces for a day
Children especially at school- are most susceptible
population.
A patient is contagious before symptoms and long time
after.
Categories at highest risk for serious complications are:
Children
Immunosuppressed
Elderly
Persons with heart and lung diseases
Smokers.

Mortality: > 90% occurs in elderly patients.

New influenza A strains are generated through mutation

and reassortment.
influenza A is able to infect and replicate in humans, birds,
and pigs (zoonose).
Co-infection of a cell with different strains of influenza A
virus allows genomic segments to randomly reassort and
form a new viral antigenic make-up, virulence property, or
host scope.
An exchange of the HA gp may generate a new virus that
can infect an immunologically nave human population.
For example, an H5N1 duck virus and an H3N2 human
virus infected pigs, reassortants were isolated from the pig,
and the resulting virus was able to infect humans.
There is concern that a reassortant between the avian, very
virulent H5N1 (that can pass directly from bird to human) and
a human influenza virus might generate a pandemic.

PROPERTIES OF
ORTHOMYXOVIRUS AND
PARAMYXOVIRUS
Property

orthomyxovirus

paramyxovirus

viruses

Influenza A,B,C

Measles,mumps,
RSV,& parainfluenza

genome

Segmented

Non segmented

Virion RNA
polymerase

yes

yes

Capsid

helical

helical

Envelope

yes

yes

size

Smaller(110 nm)

Larger( 150 nm)

Surface spikes

H&N diff. spikes

H&N same spikes

Giant cell formation

no

yes

Envelope spikes
Virus

Fusion protein

Measles virus

mumps

RSV

Parainfluenza

Paramyxovirus
Non segmented, ss genome; helical
capsid with outer lipoprotein envelope

Envelope spikes: H & N and fusion

protein

MEASLES VIRUS
Single serotype
H- target of neutralizing Ab
Humans are the natural host

Pathogenesis
Receptor: CD46 on surface of
macrophages
Rash-cytotoxic T cells attacking the virus
infected vascular endothelial cells in the
skin
CMI- neutralizing the virus during viremic
phase
MOT: droplet inhalation
Hematogenous transplacental

Clinical
Incubation : 7-13 days
Prodrome- high fever, 3C & P- infectious
Koplicks spots- buccal mucosa across
the molars- grains of salt surrounded by
red halo
Rashes appears-starts below the ears
and spread throughout the body
undergoes brawny desquamation

Complications
Encephalitis
Bacterial pneumonia
Giant cell pneumonia- defective CMI
Atypical measles- older inactivated
mealses
SSPE-subacute sclerosing
panencephalitis

Mumps virus
H and N + fusion protein on envelope
spikes
Internal nucleocapsid protein- S Antigendetected in complement fixation test
Humans are the natural host
thermolabile

Mumps
Nasal or URT epithelial cells- bloodsalivary glands, testes,ovaries, pancreas,
meninges and kidneys
Shed in the saliva 2 days before to 9
days after the onset of salivary gland
swelling
(+) virus in urine up to 14 days after onset
of symptoms

Clinical

1/3 of patients subclinical

50% with swelling of the salivary glands
Pain and anorexia
Complications
Orchitis-postpubertal-unilateral, bilateral-sterility
aseptic meningitis
Oophoritis-5%
Pancreatitis- 4%

Immunity
Ab vs HN glycoprotein- correlate with
immunity
Ab vs S Ag- appear earliest, gone w/in 6
months
Passive immunity from mother to offspringprotection during 1st 6 months of life

Diagnosis
1. cell culture

Specimen-saliva, spinal fluid or urine

Monkey kidney cell
CPE- cell rounding and giant syncytia formation

2. serology- 4 fold rise in Ab titer in HI or CF

Ab vs S antigen- current infection
Ab Vs V antigen- past infection

Prevention: vaccine, attenuated vaccine

Respiratory Syncytical
Virus
Most important cause of pneumonia and
bronchiolitis in infants
Fusion proteins- syncytia formation
Humans and chimpanzees- natural host
2 serotype: A & B
MOT: respiratory droplet

Clinical
1. infants- bronchiolitis, pneumonia
2. young children- otitis media
3. older children and adults- common
cold
Diagnosis: immunofluorescence

Isolation in cell culture- + CPE

serology

Treatment
Aerosolized Ribavirin
Ribavirin + hyperimmune globulins
Prevention
NO VACCINE
Palivizumab-prophylaxis, monoclonal ab vs.
fusion protein

Parainfluenza Virus
Surface spikes: H & N same spike, fusion
on different spike
Both humans and animals infected
Four serotypes: 1, 2, 3 & 4
MOT: respiratory droplet

 No viremia
Clinical:

1&2- major cause of croup; children < 6 y/o

Laryngitis
Pneumonia
Common cold- 4
Pharyngitis
Otitis media