Orthomyxoviruses
Influenzae A,B
&C
4/3/13
A
and B cause disease in humans, C infects humans, but does not cause disease
A
also frequently infects animals
B
only infects humans and causes less severe symptoms
-RNA
viruses-means they are enveloped
Very
similar to Paramyxoviruses except genome is segmented
8
segments-encoding 10 products
Have HA-plays role in attachment and
fusion
Neuraminidase-cleaves sialic
acid of host molecules
Both HA and N exist as trimers
Ortho enters through coated pit
formation.
Infection
and replication-
Attach
to host sialic acid by Hemagglutinin
Taken
in by endocytic vesicle
Decrease
in pH causes conformational change in HA that facilitates fusion
of viral envelope with vesicle wall
M2 (found only in type A)
promotes further acidification which allows
dissociation of NP from matrix and RNA
Genome
released into cytoplasm
RNA
migrates to nucleus where transcription takes place (mRNA & cDNA)
mRNA goes back to cytoplasm for translation
Replication
using + strand template takes place in nucleus
High
concentrations of NP will shift production to cDNA
NP,
PA, PB1 and PB2 migrate into nucleus and attach to -RNA
segments
HA,
NA and M2 go via endoplasmic reticulum for surface expression
Matrix
protein lines the inside of cell
Assembly
and budding-not very effective due to random assortment of segments
Flu-
Respiratory tract infection
ÒStomach
fluÓ is usually rotavirus, enterovirus, or adenovirus
symptoms include severe malaise, fever, myalgia,
substernum pain, photophobia
Can
lead to bacterial or viral pneumonia
Causes
loss of ciliate tissue in URT
Host
response directed against HA and NA molecules
Both
undergo genetic drift-subtle mutations
Occasionally
undergo genetic shift-rapid only in A
Designation-
There
are 15 known serotypes of hemagglutinin and 9
serotypes of neuraminidase
These
can occur in random combinations (some are much more prevalent than others)
Includes
virus type; location, month, and year of initial isolation; specific hemagglutinin and neuraminidase types if known
A/Bangkok/1/79
(H3N2)
B/HongKong/2/83
(H2N1)
A/HongKong/7/03
(H5N1)
Host
specificity, co-infection and antigenic shift
Host specificity is determined by sialic acid binding of HA
Single amino acid seems to determine
specificity
If HA aa 226 is leucine humans
can be infected
If HA aa 226 is glutamine birds can be infected
Pigs can be infected by
both
Coinfection happens when a single cell is infected
with two different viruses
Typically
pigs infected with human and avian viruses
Allows
genetic rearrangement and genetic shift
Genetic
Shift-
Result
of segmented genome and packaging
Associated
with epidemics
Dramatically
different virus emerges in short time
Prevention
and treatment
Vaccine-produced
annually based on three most likely serotypes
Very
young and very old should be vaccinated
Those
in the middle need to balance risk/benefits
Hand
washing during flu season
Virus
is very labile and will become noninfectious within 2 hours
Frequent
hand washing will decrease transmission from surfaces
Treatment-
Amantadine and rimantadine
Inhibit
ability of M2 to decrease pH
May
effect ion channels
Tamiflu and Zanamivir inhibit neuramindase activity
Zanamivir is
inhaled, Tamiflu is taken orally
Both
diminish the severity and duration of infection
Must
be taken within first 12 hours of symptoms
Avian Flu
Binding affinity to SA 2,3 Gal rather than SA 2,6 Gal from avian strains
Strains from infected humans demonstrate mutations allowing binding to SA 2,6 Gal
Already resistant to Amantadine and rimantadine
5/1/05 President signed executive order authorizing strict quarantine measures if strains capable of causing pandemic flu come to U.S.