Both orthomyxo and paramyxo viruses are RNA enveloped viruses.
Both have helical capsid symmetry.
The term Myxo refers to the ability of these viruses to interact with
mucins , that are glycoproteins on the cell surface.
Both have SS, linear and negative polarity RNA’s.
The orthomyxoviruses have a segmented RNA genome (usually 8
pieces). Paramyxoviruses have their genome as a single piece.
Orthomyxoviruses are smaller than paramyxoviruses.
Influenza viruses are the only members of this family.
These are important human pathogens as they cause
both outbreaks and pandemics (infrequently) that kill
thousands of people.
Three kinds of Influenza viruses known:
Influenza A virus causes worldwide epidemics.
Influenza B virus causes major outbreaks of
Influenza C virus cause mild respiratory tract
infections and no outbreaks.
Influenza virus genome is a segmented, SS, negative
polarity RNA with a helical nucleocapsid and an outer
The virion contains its own RNA polymerase.
The envelope has 2 different spikes, a hemagglutinin (HA)
and a neuraminidase (NA).
The function of the HA is to bind to the cell surface
receptor usually a neuraminic acid or sialic acid; to infect
the cell. The HA is highly antigenic and a target of the
The hemagglutinin functions at the beginning of
The hemagglutinin agglutinates red blood cells, and this is
the basis of diagnostic Hemagglutination inhibition test.
The neuraminidase cleaves neuraminic acid to release
the progeny virus from the infected cell.
Neuraminidase functions at the end.
Neuraminidase also degrades the protective mucosal
layer in the respiratory tract and enables the viruses
to gain entry to the respiratory epithelial cells.
Changes in the antigenicity of hemagglutinin and
neuraminidase confers on the Influenza A virus the ability
to cause pandemics.
Two types of antigenic changes are known:
1) Antigenic shift that involves a major change based on
the reassortment of segments of the genome RNA.
2) Antigenic drift signifies a minor change based on
mutations in the genome RNA.
Thus, Influenza viruses have many serotypes.
Influenza A virus have 2 matrix proteins M1 and M2.
M1 is located between the internal nucleoprotein and the
envelope and provides structural integrity.
M2 protein forms an ion channel between the interior and
the exterior of the virus. It transports protons into the
virion causing the disruption of the envelope. This leads to
the uncoating of the virus and frees the nucleocapsid
containing the RNA genome and allows it to migrate to
A non structural protein called NS-1, by its ability to
inhibit the production of interferon mRNA reduces the
host innate defence and is an important determinant of
virulence of the virus.
Many species of animals have their own Influenza A viruses
(aquatic birds, chickens, swine, horse etc…). These animal
viruses are the source of the RNA segments that encode the
antigenic shift variants and cause epidemics.
There are 16 types of HA (H1 to H16) and 9 types of NA (N1 to
N9) found in water fowl.
3 types of HA (H1 to H3) and 2 types of NA (N1 and N2) are
found in human viruses.
When two influenza A viruses from 2 different species infect the
same cell, there can be an exchange and reassortment of the
coding RNA segments leading to a new variant of the virus.
The H1N1 and H3N2 strains of Influenza A virus are the most
common at this time and they are included in the current
H2N2 caused a pandemic in 1957. H5N1 influenza A virus
(avian influenza, bird flu) caused an outbreak in 1997.
H1N1 influenza A virus (of swine origin, swine flu, Swine
origininfluenza virus / S-oiv) ) caused an outbreak in 2009.
The spread from person to person is a major concern as
the reassortment with human adapted strains would
increase the spread dramatically.
Influenza B virus is only a human virus with no animal
sources. Therefore does not undergo enough antigenic
shifts to produce pandemics, but enough to change the
strain. Hence, a new version of Influenza vaccine needs to
be produced each year.
Influenza viruses have both Group-specific and Type-
The group-specific antigen includes the internal
Ribonucleoprotein that distinguishes Influenza A,B and C
viruses. Antibodies against group specific antigens do not
offer protection against the infection.
The Type-specific antigens include the hemagglutinin and
neuraminidase present on the cell surface. Antibodies
against type-specific antigens offer protection. Antibodies
against neuraminidase only decreases the amount of viral
progeny released from the infected cell and thus reducing
After viral hemagglutinins interact with the surface
receptors, the virus enters the cell in vesicles and uncoats
mediated by the M2 proteins and is facilitated by the low
pH within the endosome/vesicle.
The viral nucleocapsid enters the cytoplasm and migrates
to the nucleus where the genome RNA (8 segments) gets
transcribed into mRNA by the viral RNA polymerase
Most RNA’s move to cytoplasm, some remain in the
nucleus to serve as a template for the synthesis of negative
polarity strand RNA genomes for the progeny, by a
different subunit of viral RNA polymerase (replicase).
Newly synthesized NP protein and Matrix proteins
bind to the progeny RNA genome in the nucleus and
the entire complex is transported to the cytoplasm.
The helical NP protein (ribonucleoprotein)assembles,
matrix protein mediates the interaction of the capsid
with the envelope, and the virion progeny is released
by budding off from the outer cell membrane at the
site where the HA and NA are located. The viral
progeny release is aided by the NA.
Influenza and retro viruses are the RNA viruses have
their replication in the nucleus.
Virus is transmitted by airborne respiratory droplets.
On inhalation of the virus, the NA degrades the protective
mucus layer and allows the virus to enter the cells of the upper
and lower respiratory tract.
This is because the protease required to cleave the
hemagglutinin into a modified hemagglutinin (that actually
mediates attachment to the cell surface)is located in the
respiratory tract. Infections are generally localized.
Systemic symptoms like severe myalgias are more due to
circulating cytokines in the blood rather than the viremia as it
Immunity depends on the secretory IgA in the respiratory tract
and cytotoxic T-cells.
Include an incubation period of 24-48 hours.
Symptoms include fever, myalgias, headache, sore throat, and
Secondary bacterial pneumonia (usually due to S.aureus) can
lead to complications.
Reye’s syndrome ( encephalopathy and liver degeneration ) is a
life threatening but rare complication (Aspirin given to reduce
fever is generally implicated in the pathogenesis of Reye’s
Clinical diagnosis is sufficient.
Virus detected in nasal/throat swabs/sputum using direct
fluorescent antibody tests, PCR or culture based tests
Rapid tests to detect viral antigens using monoclonal;
antibodies against viral antigens or to detect
neuraminidase, using a substrate for the enzyme that
changes color when cleaved. Purpose of rapid tests is for
effective treatment with neuraminidase inhibitors has to
start within 48 hours.
Oseltamivir (Tamiflu) and zanamivir both for the
treatment and prevention of Influenza. They are
neuraminidase inhibitors and limits the release and
thereby the spread of the infection.
Oseltamivir (Tamiflu) is given orally, but zanamivir is
delivered by an inhalant directly into the respiratory
Both killed and live vaccine which contains typically 2
strains of Influenza A virus (H1N1 and H3N2) and one
strain of Influenza B virus are available.
The vaccine is reformulated every year to contain
current antigenic strains.
Organisms grown in chick embryo, so individuals
having severe hypersensitivity to eggs should not
receive the vaccine.
The live vaccine contains temperature sensitive mutants
of Influenza A and B viruses.
These mutants can grow only in cooler areas (33 degrees
C) like the nasal mucosa producing the protective
secretory IgA, and not in warmer places like the lower
respiratory tract (37 degrees C). Vaccine sprayed in the
nose and only immunizes without causing any disease.
Killed vaccines are poor immunogens, hence live vaccines
preferred. Booster dose required every year.
People with chronic diseases, particularly respiratory and
cardiovascular conditions, health care personnel, should
receive the vaccine.
The Paramyxovirus family contains4 important
human pathogens : measles virus, mumps virus,
respiratory syncytial virus (RSV) and parainfluenza
As the genome RNA is of negative polarity, they are
non-infectious and carry their own RNA polymerase.
The envelope is covered with spikes,which contains a
HA, NA or a fusion protein that causes cell fusion and
sometimes hemolysis as well.
The disease is characterized by a maculopapular rash
and occurs primarily in childhood.
The nucleocapsid and genome RNA typical of
paramyxo viruses, but their envelope spike are with
HA activity and other, the cell-fusion type with
The replicative cycle is normal like other viruses.
Transmission is through respiratory droplets
produced by coughing or sneezing.
The virus has the potential to cause epidemic,
especially in populations not introduced or
immunized to the measles virus.
Supplementation of Vitamin A greatly reduces the
severity of the disease.
Enters the blood and spreads to the skin after
infecting the cells lining the upper respiratory tract
and infecting the reticuloendothelial cells, where it
The rash is primarily due to cytotoxic T-cells
attacking the virus infected vascular endothelial cells
in the skin.
Antibody mediated vasculitis may also be responsible
for the rash.
Shortly after the rash appears (3-4 days) the virus can
no longer be recovered and the patient cannot spread
Life long immunity occurs in infected individuals.
Immunity primarily through cell-mediated immunity.
The virus binds to its receptor (called CD46) on the
human macrophages and suppresses the production
of IL-12 that is necessary for cell-mediated immunity.
Thus, infection with measles virus transiently reduces
Clinical findings include incubation period of 10-14
Characterized by fever, conjunctivitis that causes
photophobia, running nose and cough.
Red lesions with a white, central dot seen on the
buccal mucosa are known as Koplik’s spots and are
The maculopapular rash spreads through out the
body in a few days and later on develops a brownish
Encephalitis is a feared complication seen in 1:1000
cases with a permanent sequeale of deafness and
mental retardation in 40% of such cases.
Measles in pregnant women leads to still birth rather
than congenital abnormalities, as it causes a more
severe disease in the fetus than rubella.
Lab diagnosis: cell culture, fluoroscent antibody staining,
Antibody rise of 4-fold in subsequent test done after 10 days is
diagnostic, PCR etc…
Clinical diagnosis is sufficient.
Live attenuated vaccine given sub-cutaneously at 15 months of
age, usually in combination with rubella and mumps vaccine.
As contains live virus, not for pregnant women and
Immune globulin to unimmunized immunocompromised
individuals early in the incubation period amy be necessary.
Mumps is characterized by the swelling of Parotid
glands. It occurs primarily in childhood.
Typical of paramyxo, but has envelope spikes with
both HA and Na activity aqnd other with cell-fusing
and hemolytic activity.
Internal nucleocapsid protein present is the soluble Santigen detected in the CFT.
Humans are the natural host.
Transmitted through respiratory droplets.
Viruses infect the upper respiratory tract and spreads
through the blood to infect the parotid glands and
spread to other organs such as testes, ovaries ,
Life long immunity after infection and the belief that
unilateral mumps will be followed subsequently again
on the other side is unfounded.
Clinical findings include incubation period of 18-21 days.
Fever, malaise, and anorexia followed by tender swelling of the
parotid glands, either unilateral or bilateral.
Complications such as Orchitis in post pubertal males, if bilateral will
lead to sterility.
Clinical diagnosis sufficient, Lab diagnosis for confirmation.
Cell culture from specimen such as saliva, spinal fluid or urine.
4-fold rise in subsequent titer and hemaagglutination inhibition or
the CFT that assays both the S-antigen and V(viral antigens).
S-antigen indiates current infection; V-antibody indicates, infection in
Live attenuated vaccine.
Given at 15 months of age and a booster after 4-6
Not for immunocompromised and pregnant women.
Respiratory Syncytial virus (RSV).
Most important cause of pneumonia and
bronchiolitis in infants.
Important cause of otitis media in children and
pneumonia in the elderly and patients with chronic
Typically paramyxo, the envelope surface spikes are
Fusion proteins alone. No HA and no NA present.
The fusion proteins cause the cells to fuse forming
multinucleated giant cells (syncytia), hence the name.
Humans are natural host and 2 serotypes known.
Transmission through respiratory droplets.
RSV outbreaks occur every year in winter, unlike
other viruses causing cold.
Pathogenesis is more severe in infants involving the
lower respiratory tract, than in older children and
adults. The cause may be immunopathogenic due to
the maternal antibody passed on by the mother which
may react with the virus, form immune complexes
and damage the respiratory tract cells.
Immunity is incomplete and the individual can have
IgA antibodies of the respiratory cells may have a
protective effect as the person ages.
Clinical findings include lower respiratory tract
diseases such as bronchiolitis and pneumonia in
children, immunocompromised, elderly and cardiopulmonary patients.
Lab diagnosis includes:
Rapid antigen test which is a enzyme immunoassay
detecting the presence of RSV antigens in respiratory
Immunofluorescence on smears of the respiratory
epithelium or by isolation in culture for further
CPE of multinucleated giant cells in cell culture is a
Combination of aerosolized Ribavirin and
immuneglobulins more effective than ribavirin alone.
Cause croup (acute laryngotracheobronchitis), laryngitis,
bronchiolitis and pneumonia in children.
Typically paramyxo. Surface spikes have HA, NA (fused
together on a single spike) and fusion proteins (separate).
Fusion proteins mediate formation of multinucleated
Transmission, CPE, etc… same like other paramyxo.
Antibody to the HA and Fusion protein neutralizes
Cause upper and lower respiratory tract diseases without
Parainfluenza 1 and 2 are major cause of Croup in children
below 5 years of age, and characterized by harsh cough
and hoarseness. Parainfluenza 3 in children and 4 causing
mild cold like symptoms are also known.
Diagnosis mostly clinical. Cell culture, PCR for
No antiviral therapy or vaccine is available.