INFLUENZA VIRUS 1 FLU True influenza influenza virus

INFLUENZA VIRUS 1

‘FLU’ • True influenza – influenza virus A or influenza virus B (or influenza virus C infections - much milder) • Febrile (showing signs of fever) respiratory disease with systemic symptoms caused by a variety of other organisms often called ‘flu’ 2

South Carolina 1996 -1997 medical bulletin no virus CULTURE RESULTS influenza A influenza B 3 http: //www. state. sc. us/dhec/LAB/labbu 017. htm

THE IMPACT OF INFLUENZA PANDEMICS Deaths: 4

THE IMPACT OF INFLUENZA • 1972 -1994 (19 influenza seasons) – >20, 000 US deaths in 11 seasons – >40, 000 US deaths in 6 of these – many more hospitalizations (~110, 000 per year) 5

THE IMPACT OF INFLUENZA • recently some increase in morbidity and mortality - possible factors? – more elderly people – CF patients live longer – more high risk neonates – more immunosuppressed patients 6

What virus causes influenza? 7

ORTHOMYXOVIRUSES • Pleomorphic – can alter shape in response to environment • influenza types A, B, C • febrile, respiratory illness with systemic symptoms 8

ORTHOMYXOVIRUSES HA - hemagglutinin NA - neuraminidase helical nucleocapsid (RNA plus NP protein) lipid bilayer membrane polymerase complex M 1 protein HA allows for viral entry into host cell NA allows for viral exit from host cell 9

TRANSMISSION • AEROSOL – 100, 000 TO 1, 000 VIRIONS PER DROPLET • 18 -72 HR INCUBATION • SHEDDING 10

NORMAL TRACHEAL MUCOSA 3 DAYS POST-INFECTION 7 DAYS POST-INFECTION 11 Lycke and Norrby Textbook of Medical Virology 1983

• DECREASED CLEARANCE • RISK BACTERIAL INFECTION • VIREMIA (when virus enters blood stream) - rare 12 Lycke and Norrby Textbook of Medical Virology 1983

RECOVERY • INTERFERON - SIDE EFFECTS INCLUDE: – FEVER, MYALGIA (muscle pain), FATIGUE, uneasiness/discomfort • CELL-MEDIATED IMMUNE RESPONSE • TISSUE REPAIR – CAN TAKE SOME TIME 13

An immunological diversion INTERFERON 14

INTERFERON timecourse of virus production will vary from virus to virus 15

INTERFERON 16

INTERFERON antiviral state 17

INTERFERON antiviral state 18

INTERFERON antiviral state 19

INTERFERON • induce various proteins in target cells • many consequences, not all fully understood • only made when needed 20

EFFECTS OF INTERFERONS – INCREASE amount of cytotoxic T-cells resent/active – ACTIVATE NK cells – ACTIVATE helper T cells 21

THERAPEUTIC USES OF INTERFERONS • ANTI-VIRAL • MACROPHAGE ACTIVATION – interferon-gamma has been tried for e. g. lepromatous leprosy, leishmaniasis, toxoplasmosis • ANTI-TUMOR • MULTIPLE SCLEROSIS 22

Viral response to host immune system Viruses may : block interferon binding inhibit NK function interfere with cytotoxic T cell response inhibit apoptosis etc! 23

SIDE EFFECTS OF INTERFERONS • • FEVER DISCOMFORT/UNEASINESS FATIGUE MUSCLE PAINS 24

BACK TO INFLUENZA 25

PROTECTION AGAINST RE-INFECTION • Ig. G and Ig. A – Ig. G less efficient but lasts longer • antibodies to both HA and NA important – antibody to HA more important (can neutralize) 26

SYMPTOMS • • • FEVER HEADACHE MYALGIA COUGH RHINITIS (inflammation of mucous membrane 27

CLINICAL FINDINGS • SEVERITY – VERY YOUNG – ELDERLY – IMMUNOCOMPROMISED – HEART OR LUNG DISEASE 28

PULMONARY COMPLICATIONS • CROUP (YOUNG CHILDREN) • PRIMARY INFLUENZA VIRUS PNEUMONIA • SECONDARY BACTERIAL INFECTION – Streptococcus pneumoniae – Staphlyococcus aureus – Hemophilus influenzae 29

MORTALITY • MAJOR CAUSES OF INFLUENZA VIRUS- ASSOCIATED DEATH – BACTERIAL PNEUMONIA – CARDIAC FAILURE • 90% OF DEATHS IN THOSE OVER 65 YEARS OF AGE 30

ANTIGENIC DRIFT • HA and NA accumulate mutations – RNA virus • immune response no longer protects fully • sporadic outbreaks, limited epidemics 31

ANTIGENIC SHIFT • “new” HA or NA proteins • pre-existing antibodies do not protect • may get pandemics 32

INFLUENZA A PANDEMICS Ryan et al. , in Sherris Medical Microbiology 33

where do “new” HA and NA come from? • 13 types HA • 9 types NA – all circulate in birds • pigs – avian and human 34

where do “new” HA and NA come from? 35

VACCINE • ‘BEST GUESS’ OF MAIN ANTIGENIC TYPES – CURRENTLY • • type A - H 1 N 1 type A - H 3 N 2 type B each year choose which variant of each subtype is the best to use for optimal protection 36

CDC 37

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