10 Orthomyxoviridae Flashcards
what is M2
core protein, has a channel through it
what are the single-stranded negative strand RNA viruses like
analysis RNA-dependent
RNA- polymerases
Many branches harbour human pathogens
what is the order of Orthomyxoviridae Family
unassigned
what is the family of orthomyxoviridae like
Straight, mucus, RNA Viruses
how many genera are there
7 genera of Orthomyxoviridae
what are the genera of orthomyxoviridae
› Influenza virus A › Influenza virus B › Influenza virus C › Influenza virus D › Thogotovirus › QuaranJAvirus › Isavirus (ISA: infectious salmon anaemia)
what can influenza type A viruses infect
man, horses, pigs, bats and birds
what can influenza type A cause
pandemics
what can influenza type B viruses infect
man and seals
what can influenza type B cause
human disease but generally not a severe as A types
Re-assortment with type A can lead to pandemics
how are influenza A and B differentiated
they are not able to be distinguished by electron microscope
what does influenza C infect
man
pig
dog
what does influenza C cause
doesn’t cause infection
how is influenza C distinguished
EM - distinguishable structures
what does influenza D infect
pigs
cattle
what is the orthomyxoviridae genome like
Segmented single stranded (-) sense RNA (8 A, B:7 C,D) (-ve sense = opposite to mRNA, cant translate directly – has to make an mRNA to translate)
what is the orthomyxoviridae lipid envelope like
- spherical sometimes filamentous (pleomorphic, change shape)
- glycoproteins + major antigenic determinants
what is the M1 protein in orthomyxoviridae like
Matrix Protein (M1) - between envelope and core
what is the core in orthomyxoviridae like
- RNP (ribonucleoprotein) complex
- ve sense RNA has various proteins that surround it: polymerase basic protein (PB1, PB2) polymerase acid protein (PA) nucleoprotein (NP)
what do viral glycoproteins bind with
Glycoproteins + major antigenic determinants haemagglutinin, trimer (Ha or H)
Binds sialic acid
what are viral glycoproteins involved in
in attachment, entry and fusion
what must happen to viral glycoproteins on exit
must be cleaved – done by neuraminidase, tetramer (NA or N)
how if flu infection caused
- virus droplets circulate in air following a sneeze
- FLU circulating in air for over an hour
- aerosol directly contact with nose/mouth
Or - aerosol directly contact fomite e.g. mobile phone and then you touch phone and then your face
what are flu symptoms
fever, headache, extreme muscular tiredness, vomiting
difference between flu and cold
- flu = fever characteristic high temperature for few days (host cell response)
- flu = severe aches
- cold = usually more stuffy nose
where does flu droplets attach
Aerosol transmission to respiratory tract via droplets attached to Sialic Acid receptors on epithelial cells
what does influenza virus cause after 1-3 days of infection
- damaged cells release cytokines (storm) causing chills, malaise, fever and muscular ache
- additional respiratory symptoms: runny nose and cough
what does influenza virus restricted to respiratory tract cause
- no viremia or spread to other tissues
- Direct viral damage
- Indirect through inflammatory
= possible bronchitis and interstitial pneumonia
what are the virus life cycle stages
- attachment
- endocytosed
- fusion and uncoating
- viral -ve sense RNA released – goes into nucleus
- post-translational processing and packaging
- budding
what happens at attachment stage
- HA binds to sialic acid (neuraminic acid) on host cell
- adapted to host sialic acid host /cell specificity
what happens at endocytosed stage
Endocytosis engulfs virion = endocytotic vesicles
what happens at fusion and uncoating stage
- Cleavage of haemagglutinin 2. Under low pH induces fusion of the 2 membranes (assisted by M2 protein)
effect of fusion of the 2 membranes in virus life cycle
Opens a pore = release virion content into cytoplasm
- RNA travel to and into the nucleus (function of the NP protein)
what is the effect of M2
affects pH (uncoating) as allows H ions through
what is the effect of antiviral amantadine
blocks this release of the vRNA by acidification
what is viral RNA
-ve sense strand
what happens when -ve viral RNA released
must make (+) sense mRNA (protein production) PB1, PB2 and PA (polymerase) - in nucleus needs to make mRNA and cRNA - RNAs helped out of nucleus into cytoplasm by NEP and M1
what is RNA always in association with
viral proteins (vRNP)
what is mRNA made for
translation
what is cRNA
copy RNA
what is cRNA made for
serves as a template for replication
what happens to mRNA segments in post-translational processing and packaging
translated
what happens to cRNA segments in post-translational processing and packaging
replicated/packaged
what happens in post-translational processing and packaging
Exit nucleus => reach assembly site => package segments (NEP-Nuclear Exit Protein)
unknown if packaging is a random or selective
what happens if packaging is random in post-translational processing and packaging
If random: (expect to get >8) 12 segments in a single flu as suggested by some scientists would suggest that any 12 go in an then 10% of the viruses would be viable
what happens if packaging is selective post-translational processing and packaging
If selective: 8 different segments would need to be packaged by a specific mechanism
what happens in budding stage
Assemble and Bud out from the apical cell membrane
reverse of entry sequence
= Cell membrane Provides envelope
what happens in budding stage when released
Need releasing as HA anchors to sialic acid receptors
NA activity for removal of sialic acid
= hence NA inhibitor as anti-virals (Oseltamir, Zanamir)
what are PB2, PB1, PA
RNA-dependent RNA polymerase complex
what do PB2, PB1, PA require
ve sense RNA to make more +ve sense RNA from the -ve sense
what is HA
receptor-binding protein haemagglutinin
what is NP
nucleoprotein
what is NA
sialic acid-destroying enzyme neuraminidase
what is M
matrix protein M1 and ion channel M2
what is NS
nuclear export protein (NEP/NS2)
host antiviral response antagonist non-structural protein 1 (NS1)
mRNA synthesis
starts 3’ end to 5’ end
+ve sense being made by -ve sense
Has a cap
what is an epidemic
localised cluster of cases
what is a pandemic
worlswide epidemic
what is antigenic drift
changes in protein by genetic point mutation and selection
what happens to virus in antigenic drift
changes shape
what is antigenic shift
changes in proteins through genetic-reassortment (nucleic acids)
what causes antigenic shift
Due to segmented genome (influenza has 8 segments)
= allows rapid and constant re-assortment between genes of different influenza viruses (“mixed/co-infections”)
what does the segmented genome of influenza mean
sudden acquisition of a gene for a completely new HA or NA
= novel subtype that spreads rapidly around the world as most or all humans have no immunity to it
= BIG CHANGE (pandemic?)
how can influenza be prevented
Vaccines
- Epidemics can be controlled by vaccines based on HA
polyvalent vaccine of several strains circulating based on surveillance data
