AWAREmed Health and Wellness Resource Center offers to Doctors and patients alike a simple solution to combating the Flu Naturally. Using food as Medicine, Herbs and botanical as medicine, Exercise and laughter as Medicine. How to Prevent and combat the flu naturally by understanding how the viruses behave?
8. TRANSMISSION
s AEROSOL
s 100,000
TO
1,000,000
VIRIONS
PER
DROPLET
s 18-‐72
HR
INCUBATION
s SHEDDING
8
9. Influenza: Who s at risk?
s Everybody
s People with greater risk:
Ø ≥ 65 years old
Ø Patients with chronic diseases
Ø Asthma/Lung chronic disease
Ø Chronic Heart Disease
s ≤ 5 years old
10. s DECREASED
CLEARANCE
s RISK
BACTERIAL
INFECTION
s VIREMIA
RARE
10
Lycke
and
Norrby
Textbook
of
Medical
Virology
1983
11. RECOVERY
s INTERFERON
-‐
SIDE
EFFECTS
INCLUDE:
s FEVER,
MYALGIA,
FATIGUE,
MALAISE
s CELL-‐MEDIATED
IMMUNE
RESPONSE
s TISSUE
REPAIR
s CAN
TAKE
SOME
TIME
11
12. interferon-‐alpha,
interferon-‐beta
interferon
receptor
induction
of
induction
of
induction
of
a
2ʼ’5ʼ’oligo
A
synthase
ribonuclease
L
protein
kinase
ds
RNA
2ʼ’5ʼ’oligo
A
ds
RNA
activated
activated
activated
2ʼ’5ʼ’oligo
A
synthase
ribonuclease
L
protein
kinase
ATP
ATP
phosphorylated
initiation
2ʼ’5ʼ’oligo
A
factor
(eIF-‐2)
mRNA
degraded
inhibition
of
protein
synthesis
12
13. ORTHOMYXOVIRUSES
HA
-‐
hemagglutinin
NA
-‐
neuraminidase
helical
nucleocapsid
(RNA
plus
NP
protein)
lipid
bilayer
membrane
polymerase
complex
M1
protein
type
A,
B,
C
:
NP,
M1
protein
sub-‐types:
HA
or
NA
protein
13
16. CAUSE:
RNA
Virus
s file:///Users/outreach/ s
The
influenza
virus,
Desktop/DESKTOP commonly
known
as
the
%202008/curr flu,
is
an
infectious
%20project/Image-‐3D disease
of
birds
and
%20Influenza%20virus
mammals
caused
by
RNA
viruses.
Commonly
confused
with
a
cold,
the
flu
is
a
much
more
severe
disease
and
http://en.wikipedia.org/wiki/Image:3D_Influenza_virus.png
caused
by
a
different
virus.
17. Key Influenza A Viral Features
Two Surface proteins(major antigens)
s Hemagglutinin (HA)
HA
s Site of attachment to host cells
• Antibody to HA is protective
s Neuraminadase (NA)
• Helps release virions from cells
NA Antibody to NA can help modify disease
•
17 severity
24. Pandemic Influenza 2009 - Natural history of swine influenza
North American Swine Influenza Eurasian Swine Influenza
(~last 12 years)
trH3N2
trH3N2
cH1N1
trH1N2
H3N2
cH1N1
trH1N1
PB2 = North Am. Avian
H1N1
PB1 = Human
PA = North Am. Avian PB2 = H3N2 swine
HA = Human PB1 = H3N2 swine
2009 swine-like H1N1
NP = Classical swine PA = H3N2 swine
American flu
NA = Human HA = Classical swine
M = Classical swine NP = Classical swine
NS = Classical swine NA = Eurasian swine
M = Eurasian swine
NS = Classical swine
25. 1918
H1N1 Spanish flu
>20 million deaths
1957
H2N2 Asian Flu
Pandemic influenza strains contain
~2 million deaths
genes from the avian reservoir
1968
H3N2 Hong Kong Flu
~700,000 deaths
1977
? H1N1 Russian Flu
2009
H1N1 American Flu
26. Neuraminidase Inhibitors
Surface glycoprotein genes “Tamiflu” “Relenza”
HA and NA
X
Release
HA NA
Master donor ER - Golgi
strain genes
AAAA
PB2 PB1 PA AAAA
AAAA
NP M
NS Packaging and Budding
Transfection of plasmids
into cells
Nucleus
AAAA
X
IFN
AAAA
Host mRNAs
Receptor binding and Entry
Uncoating
Amantadine X+
H
Endocytosis
“Symmetrel”
“Flumadine”
27. Influenza virus Reverse Genetics
viral protein
translation
cap AAAA
mRNA
RNA polymerase II (pol II)
pIICMV pABGH
ATG--------- viral cDNA -------TAA
tI pIh
RNA polymerase I (pol I)
(-) vRNA ppp
3‘ 5‘
28. why
do
we
not
have
influenza
B
pandemics?
s so
far
no
shifts
have
been
recorded
s no
animal
reservoir
known
28
35. Fusion Schematic
Fusion
Schematic
1)
HA
binds
a
cell
GP
at
a
Sialic
Acid
Binding
Site
http://ubik.microbiol.washington.edu/microm-‐pabio445/MM_445_lec3_2002_files/MM_445_lec3_2002.ppt
36. Fusion Schematic
Fusion
Schematic
1)
HA
binds
a
cell
GP
at
a
Sialic
Acid
Binding
Site
Low
pH
2)
Clathrin-‐Coated
pit
endocytoses
virion
http://ubik.microbiol.washington.edu/microm-‐pabio445/MM_445_lec3_2002_files/MM_445_lec3_2002.ppt
37. Fusion Schematic
Fusion
Schematic
1)
HA
binds
a
cell
GP
at
a
Sialic
Acid
Binding
Site
3)
Conformational
Change:
Hydrophobic
binding
of
HA
to
vesicle
membrane
Low
pH
2)
Clathrin-‐Coated
pit
endocytoses
virion
http://ubik.microbiol.washington.edu/microm-‐pabio445/MM_445_lec3_2002_files/MM_445_lec3_2002.ppt
38. Fusion Schematic
Fusion
Schematic
1)
HA
binds
a
cell
GP
at
a
Sialic
Acid
Binding
Site
3)
Conformational
Change:
Hydrophobic
binding
of
HA
to
vesicle
membrane
Low
pH
2)
Clathrin-‐Coated
pit
endocytoses
virion
4)
RNPs
are
released
into
cytoplasm
for
replication
and
transcription
(vRNA
and
mRNA)
http://ubik.microbiol.washington.edu/microm-‐pabio445/MM_445_lec3_2002_files/MM_445_lec3_2002.ppt
39. Cellular
targets
B)
Inhibitors
of
cellular
factors
that
regulate
the
virus
life
cycle
Hillaire
et
al.
(P-‐452)
Collectin
pSP-‐D
Nicol
et
al.
(P-‐449)
FLUPEP
DAS181 Budding
Adsorption
"
Packaging
Entry Posttranslational Actin
Processing Rab 11
Endocytosis Translation
Rabs, V-type ATPases
PKC
Fusion and
Release
RNP-
mRNA
Export
vRNA (-)
CRM1
Hsc70
Import
Importins
cRNA (+)
NUP153
NUPs
40. Cellular
targets
Viral
penetration
of
cellular
barriers
is
controlled
by
cellular
signaling
cascades
Budding
Adsorption
RTKs (e.g. EGFR)
Eierhoff et al. (2010)
PLoS Pathog (in press)
Packaging
PI3K Posttranslational Raf/MEK/ERK
Processing
Entry Pleschka et al. (2001) Nat Ce
Endocytosis Translation
IKK/NF-kB
Wurzer et al. (2004) Cell Micr
Wurzer et al. (2003) EMBO J.
Fusion and
Release
RNP-
mRNA
Export
vRNA (-)
Import
cRNA (+)
58. Education
and
Awareness
s Consult their physician before taking other medication, including
OTCs
s Good hygiene
s Antiviral drugs are not cures but help manage
symptoms