SM L3 Flashcards
Symptoms of Influenza
Begin 24-48hr after infection, chills
Fever for a few days (38-39 o C), headache, fatigue due to cytokine release
Aches and pains, nasal congestion, irritated watery eyes
Nausea and vomiting
Possible complications….. Tissue damage, pneumonia, bronchitis, sinus and ear infections.
What type of virus is influenza?
Negative Sense RNA Viruse
Helical Capsid
Enveloped
Belongs to orthomyxoviridae family
True or False - Influenza can be divided into 3 types
True. Influenza A, B and C
There is no single genus of influenza, but rather a family of viruses that are divided into different types and subtypes based on their genetic and antigenic properties.
Influenza A is divided into subtypes based on which two surface proteins?
H: hemagglutinin (1 Host range: 15)
N: neuraminidase 19. e.g. H5N1
Describe Infleunza A
Can infect multiple species
most virulent and most important human pathogen
can be further defined based on serotypes
Describe Influenza B
Almost exclusively infect humans; also the seal!
Does not mutate to same degree as influenza A therefore less genetically diverse
1 serotype…..immunity at early age
Describe Influenza C
Can infect multiple species, humans, pigs
Severe illness and local epidemic
Host Range of Influenza A
Host range: Birds (avian), (Major reservoir) All H & N types Swine Humans Horses Ferrets, Mink Seals, Whales
How is influenza transmitted?
Aerosol, close contact
What is influenza sensitive to?
Sensitive to pH, heat and solvents.
What are the characteristics of Influenza?
100nm…roughly spherical, though filamentous forms do occur (pleomorphic)
Segment genome
single-stranded-sense RNA
Not a single strand of nucleic acid…it consists of 8 pieces of segmented -ve strand RNA (encode 11 proteins)
> 10 genes
overlapping reading frames
helical capsid and envelope
replicates in nucleus
Name the proteins that influenza encodes
Proteins (HA, NA, NP, M1, M2, NS1, NEP, PA, PB1, PB1-F2, PB2)
Neuraminidase (NA) 19
Glycoprotein found on outside of the viral particle
Enzyme involved in the release of viral particles from cell
These proteins are the target for antiviral drugs
Haemagglutin (HA) 1-15
Lectin that mediates binding and entry of the virus to target cells
This protein is a target for antiviral drugs
Influenza genome organisation
8 segmented ss Negative RNA genome
Influenza Replication Cycle
- Virus binds via HA to sialic
acid-lipid/protein on
susceptible cell & enters
via endocytosis - virus nucleocapsid
containing the –vRNA
transported to the
nucleus - -vRNA transcribed to
complementary viral
+mRNA via vRNA
polymerase (PA, PB1,
PB2) - Viral complementary
+mRNA either
exported to
cytoplasm and
Golgi/ER and
translated
OR
remains in the nucleus.
PA - NP, PA, PB and other
viral proteins return
to nucleus and
induce new –viral
RNA and
nucleocapsid PA,
PB vRNA
polymerases - HA, NA migrate to
plasma membrane - Matrix & NS2 shutoff
replication deliver
nucleocapsid to
plasma membrane
M - Virus
assembles and
buds from cell
Host cell dies!
Why are RNA viruses prone to error?
The replication machinery of RNA viruses is error
prone, giving rise to variation.
Enveloped viruses are more tolerant to mutation than
non-enveloped viruses (Plasticity), as the capsid has to
perform a variety of functions which can not be
compromised
Two mechanisms
Antigenic drift and shift
What are the two mechanisms to antigenic variation?
Antigenic drift and shift
Antigenic Drift
Antigenic Drift= Appearance of virus with minor
changes in antigen structure
Accumulation of
mutations that
facilitate evasion of
the host immune
response
Absence of RNA
proofreading
enzymes
vRNA polymerase
1/10,000 mutation rate
Antigenic Shift
Antigenic Shift= Appearance of virus with major
changes in antigen composition
- Occurs after viruses with
segmented genomes co
-
infect and exchange
components. * Occurs in areas with high
numbers of pigs, birds and
people. e.g. parts of Asia. * Sooner or later, a
recombinant strain as lethal
as the 1918 one will appear.
When does antigenic shift occur?
- Occurs after viruses with
segmented genomes co
-
infect and exchange
components. * Occurs in areas with high
numbers of pigs, birds and
people. e.g. parts of Asia. * Sooner or later, a
recombinant strain as lethal
as the 1918 one will appear.
Name the four different flu viruses which swine flu is made up of
North American swine influenza,
North American avian influenza,
human influenza, and swine influenza virus typically
found in Asia and Europe –
“an unusually mongrelised mix of genetic sequences.“
Sialic Acid Linkages
HA binds to sialic acid (which is attached
to galactose via linkage) on surface of
host cell membranes.
* Humans express a(2, 6) linkage ->infected
by human flu
* Birds express a(2,3) linkage -> infected
by bird flu
* Swine express both sialic acid link types -
>can be infected by both human and bird
flu.
