orthomyxoviruses

Orthomyxoviridae

e.g

influenza viruses.

Paramyxoviridae

e.g

parainfluenza, mumps, measles, respiratory syncytial,

and Newcastle disease viruses

All these viruses were grouped under

myxovirus (myxa meaning mucus) due to

their affinity to mucins (glycoproteins on cell

surface as their receptors).

Enveloped RNA viruses.

The genus Orthomyxovirus includes

influenza viruses, the causative agents of

worldwide epidemics of influenza.

Human diseases associated with influenza

virus are presented in Table 1

Influenza viruses belong to the family of Orthomyxoviridae and are the causative agents of influenza, a respiratory disease in humans with well-defined systemic symptoms that occurs in sporadic, epidemic, and pandemic forms. Influenza A and B viruses cause substantial morbidity and mortality in humans and a considerable financial burden worldwide, whereas influenza C viruses cause sporadic outbreaks of mild respiratory disease, mainly in children.

Epidemic refers to an increase, often sudden, in the number of cases of a disease above what is normally expected in a population within a geographic area

Pandemic refers to an epidemic that has spread over several countries or continents, usually affecting a large number of people.

Morphology

Influenza viruses are spherical or

filamentous, enveloped particles 80–120 nm

in diameter.

It is composed of a characteristic segmented

single-stranded RNA genome, a

nucleocapsid, and an envelope (See-Fig)

Structure of influenza virus

Influenze A virus replication cycle

Influenza viruses have two types of antigens:

A. Group-specific antigens: The ribonucleoprotein (RNP) antigen, or the “soluble” antigen, is the group-specific antigen . Influenza viruses are divided into types A, B, and C on the basis of variation in this nucleoprotein antigen.

B. Type-specific antigens: The surface antigen, or “viral” antigen, or “V antigen” is composed of two virus-encoded proteins, Hemagglutinin (HA) and NA, which are the type-specific antigens.

Neuraminidase (NA)

Hemagglutinin( HA)

tetramer a trimer

a glycoprotein is composed of two polypeptides, HA1

and HA2

It consists of 100 mushroom-shaped

spikes

consists of 500 spikes triangular-shaped

inserted into the virus membrane by its

hydrophobic tail end. The distal end

contains antigenic as well as

enzymatically active sites

inserted into the virus membrane by its

tail end. The distal end, which contains

five antigenic sites (designated as HA1–

HA5), is responsible for binding of

virion to host cells.

NA causes hydrolysis of red cells agglutinates certain red cell

Antigenic variation is a unique feature of influenza virus.

The surface antigens HA and NA show variations and are primarily responsible for antigenic variations exhibited by influenza viruses. The internal RNP antigen and M protein are stable, hence do not contribute to the antigenic variations. Antigenic variations are of two types: antigenic shift and antigenic drift.

Influenza A virus shows maximum antigenic

variations.

Influenza B virus does not undergo antigenic

shift because influenza B virus is the only

human virus for which there is no animal

source of new RNA segments. However,

influenza B virus undergoes antigenic drift.

Antigenic variation never occurs in type C

influenza virus beacuse its lack of NA.

Because the influenza virus genome is segmented, genetic reassortment can occur when a host cell is infected simultaneously with viruses of two different parent strains. This process of genetic reassortment accounts for the periodic appearance of the novel types of influenza A strains that cause influenza pandemics. Influenza viruses of animals, such as aquatic birds, chickens, swine, and horses show high host specificity. These animal viruses are the source of the RNA segments that encode the antigenic shift variants that cause epidemics among humans.

For example, if a person is infected

simultaneously by an avian and human

influenza strains, then it is possible that a

genetic reassortment could occur in infected

cells in humans. The reassortment could

lead to emergence of a new human influenza

A virus, the progeny of which will contain a

mixture of genome segments from the two

strains (e.g., a new variant of human

influenza A virus bearing the avian virus HA).

Influenza virus type A can be classified into subtypes based on the variations in their surface antigens. The WHO proposed a new system of classification in 1971 and was later modified, which takes into account the nature of both the surface antigens. According to this, the complete designation of a strain will include the

(a ) type, (b ) place of origin, (c ) serial number, and (d ) year of isolation followed by (e ) antigenic subtypes of the HA

and NA in parentheses.

For example : influenza A/Singapore/1/57 (H2N2) indicates that influenza was first originated from Singapore and was isolated for the first time in the year 1957. The HA and NA antigens are H2 and N2 as shown in the parentheses.

Influenza virus is transmitted from person to person primarily in droplets released by sneezing and coughing.

Inhaled influenza viruses reach lower respiratory tract, tracheobronchial tree, the primary site of the disease.

They attach to sialic acid receptors on epithelial cells by HA present on the viral envelope.

Neuraminidase of the viral envelope may act on the N -acetyl neuraminic acid residues in mucus to produce liquefaction.

• Infection of mucosal cells results in cellular

destruction and desquamation of the superficial

mucosa.

• The resulting edema and mononuclear cell

infiltration of the involved areas are accompanied

by symptoms including cough, sore throat, and

nasal discharge, fever, muscle aches, and general

prostration.

• in patients with underlying heart or lung disease,

the infection may extensively involve the alveoli,

resulting in interstitial pneumonia, edema and

lung hemorrhage.

Incubation period is short (1–3 days).

The classic influenza syndrome is a febrile illness of sudden onset, characterized by tracheitis and marked myalgias.

Headache, chills, fever, malaise, myalgias, anorexia, and sore throat .

The body temperature rapidly rises to (38.3–40.0°C).

Sneezing, rhinorrhea, and nasal obstruction. nausea, vomiting, diarrhea, and abdominal pain.

Secondary bacterial infections:

Life-threatening influenza is often caused by secondary bacterial

infections with staphylococci, pneumococci, and Haemophilus

influenzae.

Pneumonia may develop as a complication and may be fatal,

particularly

(a) in elderly persons above 60 years with underlying chronic

disease,

(b) in people with impaired resistance (chronic cardiorespiratory

disease, renal disease, etc.).

(c) in pregnant women.

Central nervous system complications: Guillain–Barre syndrome

characterized by encephalomyelitis and polyneuritis is a

rare complication of influenza virus infection

Other complications: Reye’s syndrome is a noted complication of

influenza B infection.

◗ Specimens Specimens include

nasal or throat washings or sputum for viral antigen and viral RNA.

throat gargles for isolation of viruses.

serum for viral antibodies.

◗ Direct antigen detection A rapid, specific diagnosis of influenza is made by

demonstrating viral antigens directly on cells obtained from the nasopharynx. Immunofluorescence (IF) or enzyme-linked immunosorbent assay using specific monoclonal antibodies are used commercially to detect viral antigen.

Throat gargles are the specimen of

choice. The specimen is collected in

saline broth or a buffered salt solution

and is sent immediately to the

laboratory, or if delayed is stored at

4°C.

The virus is isolated from the specimen

by inoculation into

embryonated eggs.

cell cultures.

Demonstration of a rise in serum antibody

titer between acutephase and

convalescent-phase sera by a serological

test is diagnostic of infection.

Complement fixation test.

Hemagglutination inhibition test.

enzyme neutralization test.

radial immunodiffusion test.

ELISA are the other tests

used for demonstration of antibodies