Lecture 13 Outline
Why can I get the flu every year but only get measles once? (antigenic drift, chicken flu)
Armand clamation sneezing movie
Influenza
caused by an orthomyxovirus
spherical, ssRNA, enveloped
Three types of influenza:
Type A - common in 5-19 year olds, epidemics occur most winters
Type B - generally smaller epidemic outbreaks
Type C - rare, but can cause serious health problems
Cell surface of influenza virus
protein spikes protrude from the capsid through the lipid envelope
the two critical spikes are : hemagglutinin and neuraminidase
hemagglutinin is critical for binding of the virus to animal cells
hemagglutinin binds specific receptors on red blood cells
binding of the red blood cells causes clumping called agglutination
this agglutination process can be used to test for the virus in serum samples
neuraminidase acts to cut off the cell's hemagglutinin receptors when the progeny (new) virus bud off of the host cell
neuraminidase is not important in binding the virus to animal cells
neuraminidase also acts to degrade mucous in the animals lungs and airways that usually help protect against invasion of the lungs
Influenza infection cycle
flu is usually contracted by exposure through an infected individual
the virus can be carried in aerosols from coughs or sneezes
once in the body, the virus uses hemagglutinin to bind to a cell surface
the viral and cellular membranes fuse and the capsid is released in the cell
the viral RNA then uncoats (the protein capsid disassembles)
the viral RNA takes over cellular functions and produces viral proteins and RNA copies
hemagglutinin and neuraminidase are made and migrate to the cell membrane
the virus then assembles near the cell membrane
new progeny virus bud off of the cell membrane
Antigenic changes
hemagglutinin is on the viral surface and critical for binding to cells and infection
if the immune system was to make antibodies against the hemagglutinin antigen then the virus would not cause infection and the person would be immune
unfortunately, the hemagglutinin can undergo changes that essentially cause it to be a new antigen and thus escape previous immunity to influenza virus
small changes in the viral genome can lead to small changes in the viral surface antigens
often times only a single nucleotide in one gene is changed - a "point mutation"
these minor changes lead to epidemics, since some populations have never seen an influenza virus with this slightly altered viral surface antigen
these minor changes in antigenicity are referred to as antigenic drift
drift is seen in both type A and type B influenza and is due to natural selection of variants
major changes are also seen in the surface antigens of influenza
here, large pieces of the viral genome are exchanged with genomic material from a different strain of influenza virus
the influenza virus has 8 segments, or eight pieces of RNA
if an animal cell is infected with two different strains of influenza the 8 RNA segments from each virus can intermix
this process is called reassortment
thus, if virus A has hemagglutinin type 1 (H1) and neuraminidase type (1) and the second virus, virus B, has hemagglutinin type 2 (H2) and neuraminidase type 2 (N2), the progeny virus could have these configurations:
H1N1, H2N2, H1N2, H2N1
if a population has never seen H1N2 then a massive epidemic, called a pandemic, could ensue
these large changes are called antigenic shift and are seen in type A only
it is likely that the new viral antigen derived from an animal virus
thus a person living in close contact with a pig might be infected with a pig influenza at the same time as being infected by a human influenza
reassortment can then occur and new type of influenza created
this may lead to a pandemic
Historical antigenic shifts
there have been several antigen shifts during the last century
1901-1917 - H3N2
1918-1928 - H1N1 - Spanish flu, 1918 pandemic, H1 from swine
1929-1946 - H0S1 - first isolated human influenza virus
1947-1956 - H1N1 -
1957-1967 - H2N2 - Asian flu pandemic
1967-current - H3N2 - Hong Kong flue pandemic
1977-current - H1N1 - recurrence of a virus seen earlier
1997-current - H5N1 - chicken flu
vaccines are prepared each year for the US by looking at what strains are prevalent in the southern hemisphere winter
this year's flu vaccine has specific variants of H3N2, H1N1, and Type B influenza
