Influenza virus:



College of Medicine Microbiology

RNA viruses

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Influenza virus:

General properties:

• Shape of virus is spherical, symmetry of nucleocapsid is helical.

• Viral genome is segmented ssRNA(7– 8 segments).

• Enveloped(bi-layer membrane)

• Spiked: 2 types of proteins:H(Hemagglutinin) and N( Neuraminidase).

Classification and nomenclature:

Influenza virus classified into three types according to group-specific antigens (nucleocapsid antigens): influenza A, B and C.

Influenza type A and B contain 8 segments, while influenza type C has 7 segments of ssRNA.

The influenza type A (only) can be divided into subtypes(serotypes) according to species-specific antigen( H and N antigens). So far, 15 subtypes of H (H1-H15) and 9 subtypes of N(N1-N9).

Standard nomenclature system for influenza virus include; type, host, geographic, strain number, and year of isolation. For example: A/swine/Iowa/15/30(H1N1).

Source and transmission:

• Host range : Influenza A has broad host range capable of infecting human, swine, horses ,chicken and birds(aquatic birds). Influenza B and C host range is limited to human only.

• Infected humans are main reservoir of infection. The virus transmitted from person to person by air-borne respiratory droplets and by contact with contaminated materials of patient.

• Avian influenza virus(influenza-A) cause bird flu in domestic poultry birds, subtype H5N1can be transmitted from birds to humans, H5N1 enable to kill half of people who become infected. Fortunately avian virus was poorly transmissible to human.

Antigenic variation:

Because viral genome is segmented, genetic reassortment can occur during viral replication. The reassortment could lead to emergence of new human virus(new strain), the progeny of which will contain a mixture of genome segments from human and from animal strain. Therefore antigenic variation can occur due to mutation in sequence of amino acids in proteins of H and N . The mutation leads to change in antigenic nature of H or N or both resulting new strains that non-identified by immune system(escape from immune recognition).

Two types of variation are known:

• Antigenic shift( complete change in H or N or both). This can only occur with influenza type A because it has wide host range , when two viruses co-infect the same cell (one human strain and another animal strain), during viral replication ,the RNA segments can be mis-packaged into another virus and release new strains. Antigenic shift is responsible for influenza pandemics.

• Antigenic drift(partial changes). This occurs in type A and B. It involves minor changes affecting H or N, not both. It is responsible for influenza epidemics.

N.B: Antigenic change not appears in birds, perhaps because of their brief life span.

Antigenic variation of envelope proteins H and N is responsible for epidemic and pandemic diseases. Influenza A cause major epidemic disease(pandemic) with significant mortality. Influenza B cause sporadic and periodical epidemic disease, usually milder than influenza A. While the influenza C cause minor (mild), sub-clinical disease, because it stable antigenic and lack neuraminidase gene (the gene is located on segment which the type C hasn’t it).

Pathogenesis:

• Virus is limited to ciliated epithelial cells of respiratory tract, leading to cell death. Denudation of respiratory epithelium causes acute inflammatory response and renders the individuals to bacterial super-infections.

• N antigen facilitates infection by reducing the viscosity of mucus lining by cleaves neuraminic acid( the substrate covering mucosal epithelial cells of respiratory tract) and disrupts the mucin barrier ,then exposing the cell receptor for virus absorption( H responsible for absorption). H antigen can attach to receptor on epithelial cells resulting in gulf of virus by endocytosis and in dumping of viral genome into host cell.

• Within short time many cells in respiratory are infected and killed. The virus replicates within nucleus of infected cell and result in shut-off of host cell protein synthesis by 3 hr. and new progeny viruses are produced within 8-10 hr.s

• The virus remains localized to respiratory, hence viremia does not occur.

• Antibodies provide long-lasting immunity (not long life immunity) against influenza infection.

C/F:

• IP(1-4 days) dependent upon size of dose and immune status of human. Fever ,headache, nose secretion, anorexia, cough and generalized myalgia(muscle pain) are most clinical features. If no complication, the disease resolve in 2-7days.

• Complication of influenza ; individuals at greater risk for complication include elderly and immunocompromised people, the virus spreads to LRT , resulting in secondary infection such as bacterial pneumonia caused by Strep.pneumoniae ,Staph.aureus or Hemophilus influenzae .

• Other viruses; parainfluenza viruses are responsible for 10% respiratory infections in children. They are classified into 4 types. They cause influenza-like illness with croup.

Epidemiology:

• Influenza occurs primarily in winter months, when it and bacterial pneumonia secondary to influenza cause a significant number of deaths especially in older people. In southern hemisphere, eg. in Australia and New Zealand , influenza occurs in winter months of June through August.

• Influenza has been responsible for millions of infection worldwide. Most cases due to type A. It is estimated 3-5 millions infected cases.

• Influenza occurs worldwide distribution (epidemics) . Influenza outbreak occurs in wave. The period between epidemic wave of influenza A tend to be 2-3 years, type B is longer 3-6 years . Pandemic disease occurs every 10-40 years. Shift variants appear every 10 years, whereas drift variants appear every year (approximately).

• Global influenza infection(epidemic):

1889 H2N2

1900 H3N2

1918 H1N1(Spanish flu)

1947 H1N1

1957 H2N2(Asian flu)

1968 H3N2(Hong Kong flu)

1977 H1N1(Russian flu)

1997 H5N1

1999 H9N2

2004 H5N1

2006 H5N1

2009 novel strain contains mixed genome (originated from bird as well as from swine and human).

Lab.Dx:

• Virus is isolated from clinical specimen(nasal washings, gargles and throat swabs) in cell culture.

• Detection of specific antibodies level over 2 weeks by serological tests : CFT and ELISA

• Detection of viral nucleic acid by PCR.

• Detection of viral proteins.

Control methods:

a. Treatment:

• Amantadine and Rimantadine are used to prevent uncoating of influenza A. Whereas Sanamavir (inhaled) and Oseltamivir (oral) are inhibitors for neuraminidase in influenza A and B.

• Children given aspirin(salicylate) when they have influenza can develop a severe liver and brain disease called (Reye syndrome). Give acetaminophen for fever in children, no aspirin.

b. Prevention:

• Influenza virus vaccine (killed vaccine) has been used to prevent infection, primarily influenza A and B. It given intramuscularly for elderly and immunocompromised patients. Attenuated influenza A vaccine (given intra-nasally ;spraying into nose ) is available for healthy adults and children. Because the virus undergo antigenic shift, the vaccine will not be effect in protecting against the new subtypes of virus . Therefore, it becomes necessary to develop a new vaccine as quickly as possible.

• Personal hygiene and avoid contact with patients.

• Avian virus was controlled by destroying poultry.

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