ORTHOMYXOVIRUS

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. It’s 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, and M2 proteins, which are
transcribed from one segment each.
Antigenic Shift and drift phenomenon of influenza
v.:
The HA has several functions:
1. attachment protein, bind to sialic a. cell receptors
2. promotes fusion of envelope to cell membrane
3. hemagglutinates human RBCs
4. it elicits the protective neutralizing antibody response.

HA & NA of ONLY influenza A virus can undergo

major antigenic changes (called: shifts, due to RNA
segment reassortment)…
Minor changes (called: drift, due to gene 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 naïve 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 yes yes
polymerase
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 H N 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
 Koplick’s 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 Antigen-
detected in complement fixation test
 Humans are the natural host
 thermolabile
Mumps

 Nasal or URT epithelial cells- blood-

salivary 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 offspring-
protection 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