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INFLUENZA VIRUS

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‘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’

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South Carolina 1996-1997 medical bulletin

http://www.state.sc.us/dhec/LAB/labbu017.htm

no virus

influenza A

influenza B

CULTURE RESULTS

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1918-19 Spanish flu 500,000 US20,000,000 world

1957-58 Asian flu 70,000 US

1968-69 Hong Kongflu

34,000 US

THE IMPACT OF INFLUENZAPANDEMICS

Deaths:

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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)

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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

What virus causes influenza?

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ORTHOMYXOVIRUSES

• Pleomorphic – can alter shape in response to environment

• influenza types A,B,C• febrile, respiratory

illness with systemic symptoms

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ORTHOMYXOVIRUSES

M1 protein

helical nucleocapsid (RNA plus NP protein)

HA - hemagglutinin

polymerase complex

lipid bilayer membrane

NA - neuraminidase

HA allows for viral entry into host cell NA allows for viral exit from host cell

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TRANSMISSION

• AEROSOL– 100,000 TO

1,000,000 VIRIONS PER DROPLET

• 18-72 HR INCUBATION

• SHEDDING

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NORMAL TRACHEAL MUCOSA

3 DAYS POST-INFECTION 7 DAYS POST-INFECTION

Lycke and Norrby Textbook of Medical Virology 1983

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• DECREASED CLEARANCE

• RISK BACTERIAL INFECTION

• VIREMIA (when virus enters blood stream) - rare

Lycke and Norrby Textbook of Medical Virology 1983

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RECOVERY

• INTERFERON - SIDE EFFECTS INCLUDE:– FEVER, MYALGIA (muscle pain), FATIGUE,

uneasiness/discomfort

• CELL-MEDIATED IMMUNE RESPONSE

• TISSUE REPAIR– CAN TAKE SOME TIME

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An immunological diversion

INTERFERON

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INTERFERON

timecourse of virus production will vary from virus to virus

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INTERFERON

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INTERFERON

antiviral stateantiviral state

antiviral state

antiviral state

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INTERFERON

antiviral stateantiviral state

antiviral state

antiviral state

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INTERFERON

antiviral stateantiviral state

antiviral state

antiviral state

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INTERFERON

• induce various proteins in target cells

• many consequences, not all fully understood

• only made when needed

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EFFECTS OF INTERFERONS

– INCREASE amount of cytotoxic T-cells resent/active

– ACTIVATE NK cells– ACTIVATE helper T cells

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THERAPEUTIC USES OF INTERFERONS

• ANTI-VIRAL • MACROPHAGE ACTIVATION

– interferon-gamma has been tried for e.g. lepromatous leprosy, leishmaniasis, toxoplasmosis

• ANTI-TUMOR• MULTIPLE SCLEROSIS

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Viral response to host immune system

Viruses may :

block interferon binding

inhibit NK function

interfere with cytotoxic T cell response

inhibit apoptosis

etc!

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SIDE EFFECTS OF INTERFERONS

• FEVER

• DISCOMFORT/UNEASINESS

• FATIGUE

• MUSCLE PAINS

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BACK TO INFLUENZA

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PROTECTION AGAINST RE-INFECTION

• IgG and IgA– IgG less efficient but lasts longer

• antibodies to both HA and NA important– antibody to HA more important (can

neutralize)

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SYMPTOMS

• FEVER

• HEADACHE

• MYALGIA

• COUGH

• RHINITIS (inflammation of mucous membrane

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CLINICAL FINDINGS

• SEVERITY– VERY YOUNG– ELDERLY– IMMUNO-

COMPROMISED– HEART OR LUNG

DISEASE

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PULMONARY COMPLICATIONS

• CROUP (YOUNG CHILDREN)• PRIMARY INFLUENZA VIRUS

PNEUMONIA• SECONDARY BACTERIAL

INFECTION– Streptococcus pneumoniae– Staphlyococcus aureus– Hemophilus influenzae

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MORTALITY

• MAJOR CAUSES OF INFLUENZA VIRUS- ASSOCIATED DEATH– BACTERIAL PNEUMONIA– CARDIAC FAILURE

• 90% OF DEATHS IN THOSE OVER 65 YEARS OF AGE

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ANTIGENIC DRIFT

• HA and NA accumulate mutations– RNA virus

• immune response no longer protects fully

• sporadic outbreaks, limited epidemics

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ANTIGENIC SHIFT

• “new” HA or NA proteins

• pre-existing antibodies do not protect

• may get pandemics

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INFLUENZA A PANDEMICS

Ryan et al., in Sherris Medical Microbiology

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where do “new” HA and NA come from?

• 13 types HA• 9 types NA

– all circulate in birds

• pigs– avian and human

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where do “new” HA and NA come from?

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VACCINE

• ‘BEST GUESS’ OF MAIN ANTIGENIC TYPES– CURRENTLY

• type A - H1N1• type A - H3N2• type B• each year choose which variant of each

subtype is the best to use for optimal protection

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CDC

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