Orthomyxoviridae

Orthomyxoviruses group of highly contagious human pathogenic viruses, cause influenza in humans & many other animals. General characteristics & structure Orthomyxoviruses are enveloped single stranded RNA viruses ~ 100 nm in diameter, they are spherical or pleomorphic. 1.Genome Consists of single stranded (-)sense RNA in 8 segments (7 in Influenza C). 2.Envelope a lipid bilayer with inserted hemagglutinin(H) & neuraminidase(N) glycoprotein spikes that project to outside. Hemagglutinin is the component of the viral membrane that attaches to specific receptor on susceptible cell. The H & N spikes are immunogenic, antibodies react with the hemagglutinin inhibit hemagglutination & neutralize viral infectiveness.

3. Influenza virus particles contain different structural proteins. (a)-Nucleoprotein (NP) associated with viral RNA to form (RNP). which assume a helical configuration. (b)-Three large proteins (PB1,PB2, & PA) bound to RNP & responsible for RNA transcription & replication. (c)-Matrix (M1) protein, forms a shell underneath viral lipid envelope form a major component of the virion. (d)-M2 ion channel protein which present in the viral envelope.

Classification of Influenza viruses Based on the antigenic difference in group antigen & difference in matrix protein influenza viruses are divided into (1) Influenza type A infect a wide variety of mammals, including man, horses, pigs, & birds. The main human pathogen, associated with epidemics & pandemics. There are 16 known haemagglutinin (H) serotypes & 9 known neuraminidase (N) serotypes. Pigs & birds are important reservoirs, generating pools of diverse viruses which get transferred back to the human population.(close contact between pigs & man in the far east; ducks - migration!). (2) Influenza type B infect mammals only & cause disease, but generally not as severe as A types. Unlike influenza A viruses, influenza B viruses do not have distinguishable serotypes. (3) Influenza type C also infect mammals only, viruses cause mild illness in humans & do not cause epidemics or pandemics.They are genetically & morphologically distinct from A & B types.

Nomenclature of Influenza viruses Viruses are designated by the major group, host of origin, location of 1st isolation, strain number & year of isolation followed by HA, & NA composition of the virus : e.g. A, swine, Iowa/ 15, 30, H1N1.

Pathogenesis & clinical findings Spread by aerosols - very efficient (occasionally fomites). Primary infection involves the ciliated epithelial cells of the U.R.T. viral replication occur in these cells.( viremia is not a manifestation of influenza).ciliated epithelial cells of the U.R.T After a very short incubation period (1-2) days necrosis of these cells results in the usual symptoms (fever, chills, muscular aching, headache, prostration, anorexia). Systemic manifestation of influenza due to viral antigens, which are toxic lead to liberation of endogenous pyrogens & host cells interferons. Normally infection is self-limited usually lasts 3-7 day. Death from primary influenza infection is very rare & appears to be determined by host factors rather than 'virulence' of virus. Damage to respiratory epithelium predisposes to secondary bacterial infections which accounts for most deaths.

Epidemiology Influenza outbreaks occur every year, extent & severity depend on the antigenic composition of the infecting virus. Influenza A outbreaks most common, Influenza B outbreaks less,while influenza C infrequently associated with human disease. Epidemics most frequently in winter. Transmission through respiratory droplet (sneezing or coughing) Outbreaks of influenza results from change in antigenicity of the virus, we have two types of Ag changes in influenza viruses. 1) Antigenic shift a major change in antigenicity of either hemagglutinin or neuraminidase or both Antigenic shift occur by dual infection of two different strains of the virus in a single host. This results in a genetic reassortment of various subunits of RNA genome with high recombination frequency.

Genetic reassortment of various subunits can result in formation of a new virus.(new strain). Many of these changes occur in orient countries & arise in ducks or other birds that live close to the humans. Antigenic shift with type A influenza may occur ~ every years, result in worldwide pandemic, whereas major changes in type B occur less frequently. (2) Antigenic drift a minor antigenic changes, occur frequently in influenza viruses, may result from only one or two aminoacids substitutions, due to point mutation in the genome, which occur sporadically, they occur frequently in hemagglutinin, this minor changes, alter the antigenic binding site lead to escape the host immune response. This antigenic drift result in virus variants,which are responsible for continuing epidemics of influenza.

Diagnosis (1) Viral isolation inoculation of the throat washings or nasal swabs into cell culture or hen eggs, after appropriate incubation, testing for hemagglutinins to identify the viral antigens. Specific identification by using hemagglutination inhibition assay with known antiserum. (2) Serology by CF or hemagglutination inhibition test to detect titer of specific antibody to influenza virus. (3) Immunofluorescence of infected cells from nasopharynx to detect viral antigen in these cells.

Treatment Several anti-influenza drugs exist. 1-Amantadine & rimantadine are active against influenza A viruses (but not B viruses). They are believed to block cellular membrane ion channels.  The target for both drugs is the matrix protein (M2).  2-Neuraminidase inhibitors These drugs work against all strains of influenza A & B Tamiflu (oseltamivir phosphate) is an inhibitor of neuraminidase taken in pill form which has been shown to confer decreased severity & duration of symptoms. Relenza (Zanamivir) must be inhaled.

Prevention: Vaccination is recommended for patients with underline disease known to associated with more sever infection. Vaccines consist of killed inactivated virus & are formulated each spring depend on the anticipated viral strain in population, so the vaccine included the three prevalent strains two most recent influenza type A strains & most recent B strain. Vaccine injected s.c. & effective for 60-80% of population for 6 months. Because it is killed vaccine it need annual boostering to maintain immune status,& those allergic to egg protein is contraindicated to use the vaccine. The 2005–06 trivalent influenza vaccine for the United States contain: A/New Caledonia/20/99-like (H1N1), A/California/7/2004-like (H3N2), and B/Shanghai/361/2002-like viruses.

Other preparation for vaccination 1-Viral sub-unit vaccine (split virus) Containing purified NA, HA, this vaccine used particularly in children < 13 years of age. Ab to HA can neutralize the virus, complete inhibit infection & Ab to NA result in reduction of virus replication decrease transmission & reduce symptoms. 2-Attenuated live virus vaccine These are frequently temperature sensitive mutants that don’t replicate beyond the superficial epithelial cells in nasopharynx, which can administered by aerosol, but bs. of the danger of attenuated virus refitting to virulence strain, Live attenuated virus vaccine have not been adopted for general uses. 3- Recombinant vaccine A major effort to develop recombinant vaccines & genetically engineered strains of virus that will protect against the disease.