Orthomyxoviridae Is enveloped virus, helical nucleocapsid and segmented (-RNA) genome comprises the influenza virus. Key viral proteins: 1) Envelop glycoprotein: are the major antigen for influenza virus. -a) Haemogglutinin (HA) functions are viral attachment protein and also binds to an aggregates erythrocytes (hemagglutination)

Key cont… b) Neuraminidase (NA): an enzyme that removes sialic acid from virion and host glycoproteins and glycolipids facilitates release of virions from target cells by minimizing clumping. 2. Nucleoprotein and RNA dependent RNA polymerase associated with genomic segment to form helical nucleocapsids. 3. MI ( Matrix protein surrounds the nucleocapsid and is involved in virion assembly. 4. M2 (membrane) protein which forms channel that facilitates uncoating and assembly, is target for amantadine and rimantadine antiviral drugs

Types and Genetics changes in influenza viruses Three types A, B and C Influenza type A&B are significant human pathogens Influenza while type C is less important. Type A influenza infect human as well as animals. a) antigenic drift: minor changes due to mutation in the genes encoding HA or NA , which alters viral antigenicity. Both Influenza A and B exhibit antigenic shift. b) Antigenic shift: major changes that result reassortment of genome segments from different human and / or animal strain.

Only influenza A undergoes antigenic shift Randon mixing and packaging of genome segments into virions occur after co – infection with different strains of viruses, producing new hybrid viruses. For example: reassortment of swine influenza virus (genome segment S1-8) and human influenza virus (segment H1-8) could create a new, distinct hybrid strain that contain some swine and some human segments and is capable of infecting humans.

Replication Attachment and entry: after HA binds to sialic- acid containing receptors on epithelial cells, virions enter by endocytosis. Fusion with endosome and un-coating: release of the nucleocapsid from internalized virion is facilitated by acidification of the endosome and M2 proton channel Nucleic acid synthesis: following release nucleocapsid, viral RNA polymerase carried in the virion moves to the nucleus where it produces mRNA and progeny genome segment.

Replication cont…… Enveloped: after nucleocapsid assemble, they move to the plasma membrane, associated with matrix protein, become surrounded by virus- modified membrane , and are released by budding.

Laboratory identification Elisa Hem adsorption Hemagglutination

Pathogenesis and host response Killing of ciliated and mucus secreting epithelial cells results from initial infection of upper respiratory tract. Action of viral neuramidase (NA) thins out mucous secretion, comprising airway clearance and promoting viral spread to the lungs, as well as secondary bacterial infections. Virus or bacteria induced tissue damage can cause pneumonia.

Interferons produced in response to infection help control viral spread but are largely responsible for typical “flu like” symptoms. Strain – specific antibody response to HA and NA antigens provides no protection against subsequent infections by different strains Cell mediated response, which recognizes peptides from less variable proteins (eg nucleoprotein) provide more general protection that can help reduce subsequent disease by different strain.

Diseases due to Influenza viruses 1. Classic acute influenza in adult: a) Time course: incubation period is 1-3 days. Prodromal period is 3- 24 hours , diseases usually lasts about 1 week. b) Clinical manifestations: malaise and head ache during prodrome are followed by myaglia, fever, and non-productive cough. Secondary bacteria infection (eg. Sore throat) may occur in the second week.

C) Severity: diseases may be asymptomatic to severe depending on the degree of existing immunity to the infecting strain and other factors Severe illness occurs most often in pregnant women and in patients with immunodeficiencies or cardiorespiratory diseases.

Epidemiology Influenza epidemics involving all age groups occur each winter; worldwide pandemics appear irregularly. Changes in the hemagglutinin and neuraminidase surface antigens are responsible for the appearance of antigenically novel strains that evade host immunity and cause reinfections

Childhood influenza Post influenza: disease is similar to that in adult but with higher fever, croup, otitis media, bronchitis, abdominal pain, and vomiting are like to be present Complications: post-influenza encephalitis with inflammation may occur 2-3 weeks after recovery, rarely fatal. Myositis and aspirin associated Rey _Syndrome may occur in children

Transmission Respiratory droplets: are primary means of spreading influenza virus. a) Local outbreak (epidemics) due to antigenic drift (change in viral antigenicity ) occurs every few years. B) Widespread outbreak (pandemic) due to antigenic shift (appearance of new strain) occur approximately every 10 years

Prevention and Treatment, 1. Formalin – killed flu vaccine consisting of the predicted endemic strain is produced each year year Immunization is recommended for at risk population particularly elderly, immunodeficient patients and those with cardiorespiratory diseases.

Treatment cont… Amantadine and rimantadine: they block uncoating of endocytosis virions, are approved for use against influenza A in unimmunized individuals but are ineffective against influenza B. Treatment must start before or within 24 to 48 hours of appearance of symptoms Zanamivir and oseltamivir inhibit neuraminidase and are effective against both influenza A &B. Acetaminophen(not asprin) can reduce symptoms of influenza

H1N1 caused "Spanish Flu" and the 2009 swine flu outbreak (novel H1N1) The Influenza A virus subtypes that have been confirmed in humans, ordered by the number of known human pandemic deaths, are: H1N1 caused "Spanish Flu" and the 2009 swine flu outbreak (novel H1N1) H2N2 caused "Asian Flu" H3N2 caused "Hong Kong Flu" H5N1 is "bird flu", endemic in avians H7N7 has unusual zoonotic potential H1N2 is currently endemic in humans and pigs H9N2, H7N2, H7N3, H10N7