L17 - GL Smith - Influenza and Hepatitis viruses Flashcards
describe influenza’s genome
-ve sense ssRNA genome with 8 RNA segments.
does influenza hace a lipid ,membrane?
yep
which ion channel does flu have?
M2
which glyocoproteins does influenza express on its surface?
haemagglutinin (HA), neuraminidase (NA)
influenza:
Beneath the virus envelope is the ____(_) protein and within the nucleocapsid the _______ (NP) is associated with the RNA genome.
Beneath the virus envelope is the matrix (M1) protein and within the nucleocapsid the nucleoprotein (NP) is associated with the RNA genome.
describe influenzas polymerase
Virion core also has PB1, PB2 and PA that make up the virus RNA-dependent RNA polymerase (RdRp). The RdRp must be packaged within the virion to transcribe the –ve sense ssRNA genome into the virus mRNAs to initiate the infectious cycle
is influenza spherical?
yes, roughly, if grown in cell culture
However, fresh clinical isolates can have a filamentous morphology.
where does influenza replicate?
is this special
Unlike most –ve sense ssRNA viruses, influenza virus replicates in the nucleus.
flu:
There are __ HA types and _ NA types.
There are 18 HA types and 11 NA types.
Most HA sub-types have been found in _ that are the natural reservoirs of most influenza viruses.
Most HA sub-types have been found in birds that are the natural reservoirs of most influenza viruses.
describe influenza transmission characteristics
transmitted via aerosol and inhaled virions initiate infection in the respiratory tract.\
Influenza transmission is highly seasonal with epidemics occurring during winter months when people are closer together inside.
label
how does flu enter the cell?
HA binds sialic acid
endocytosis
acidification in endosome causes 2 changes
- a conformational change in the HA that promotes fusion of the virus and endosomal membrane.
- enabled by low pH is the import of protons into the virus core via the M2 ion channel. This destabilises the core and promotes un-coating.
label
is HA a dimer or trimer?
trimer
describe HA structure
trimer and each monomer is composed of HA1 and HA2 subunits that are derived by proteolytic cleavage from a precursor called HA0
HA:
The HA2 subunit provides ….
The HA2 subunit provides the stalk between the globular head and the virus membrane, in which it is anchored.
describe how acidification enables HA to cause fusion of virus and endosome
HA2 contains fusogenic peptide buried in trimer. Acidification causes conformational change, exposure of fusion peptide and its insertion into host membrane
just FYI
in flu’s entry to the cell - what channel enables the import of H+ ions
M2 channel
how do they drugs amantadine and rimantidine work?
block M2 pore
prevent protonation of the core and virion uncoating
describe the process of protein replication for flu
nucleocapsid transported to nucleus
RdRp transcribes each –ve sense ssRNA segment into a mRNA
each segment codes for one protein, but for RNA segments 7 and 8, the mRNA may be spliced to produce different proteins (M1 and M2 from segment 7, and NS1 and NS2 from segment 8).
describe cap snatching in flu
The 5’ end is derived by cap-snatching from host mRNAs. That is why host DNA-dependent RNA polymerase II activity is needed for influenza replication – to provide the supply of caps that influenza virus RdRp steals to synthesise virus mRNAs.
ngl im not all thta sure
how does influenza leave teh cell?
budding
why is NA essentail for releasE?
– NA removes sialic acid from cell surface
– So new virions not bound via HA to cell surface
– NA also removes sialic acid from virions. Prevents virions clumping: HA would bind to sialic acid on HA or NA (glycoproteins)
NA is the target of which drugs?
NA is the target of anti-influenza virus drugs tamiflu
(oseltamivir) and relenza
Release of the virus requires the neuraminidase (NA) that cleaves ________ ___ residues from proteins
Release of the virus requires the neuraminidase (NA) that cleaves sialic acid residues from proteins
how does tamiflu work?
Tamiflu is an analogue of sialic acid and inhibits neuraminidase so that influenza virus cannot be released from the infected cell
2 ways flu is able to cause repeat infections?
antigenic drift and shift
to escape antibodies
describe antigenic drift in HA for flu
is HA the target for antibodies?
yep
describe antigenic shift
cell infected with 2 flu viruses - eg humand and avian - reassortment can occur
what do yo uknow about the H5N1 flu virus
in birds
can spread to humans
60% mortality rate
not aquired human to human spread
PB2 mutations affecting influenza replication.
36
what do you know about NS1 (flu)
The non-structural protein 1 (NS1) confers resistance to interferon-mediated inhibition of influenza virus replication. Avian influenza virus NS1 proteins are well adapted to do this in the avian system, but may be less efficient in humans. So the NS1 protein may adapt and become a more potent inhibitor of human IFN system and so increase virus virulence for man.
are the hepatitis A B and C similar viruses?
no. theyre very differnet viruses - but they all infect the liver
Hepatitis A virus (HAV) - describe
A picornavirus transmitted by the faecal-oral route
describe the genome of HAV
+ve ssRNA genome
Is HAV envoloped?
nope
describe capsid strcuture of HAV
Icosahedral
stable at pH 1
describe HAV transmission
describe the disease cuased by the HAV
for HAV - what percentage of children are asymptomatic
90%
how do we prevent against HAV
what type of virus is Hep B
hepadnavirus
is Hep B a DNa or RNa virus?
DNA virrus
does Hep B replicate via reverse transcription>
yep
3 main things Hep B causes
It causes acute and chronic hepatitis and hepatocellular carcinoma (HCC)
describe Hep B strucutre / lipid envelope
Icosahedral capsid, lipid envelope,
surface glycoprotein (HBsAg)
does the Hep B virus grow in cultured cells?
Virus does not grow in cultured cells
HEP B pictuet
describe HBV genomes
The HBV genome is ____kb. The genome packaged into virions is ____ DNA, partially __, and has _ overlapping open reading frames, so making efficient use of the coding potential.
The HBV genome is 3.2 kb. The genome packaged into virions is circular DNA, partially ds, and has 4 overlapping open reading frames, so making efficient use of the coding potential.
what does the HBsAg do in HBV?
HBsAg gene encodes the surface glycoprotein (HBsAg) that comes in 3 forms with differing N termini, and the ORF X encodes a transactivating protein.
HBsAg binds to hepatocytes to start infection
is the target for neutrilising antibodies
(antigen used in HBV vaccine)
describe HBV genome replication
reverse transcription
differs from retroviruses in that:
- it packages DNA, not RNA, into the virus particle,
- it does not integrate its genome into the chromosome of the infected cell as part of its replication cycle, whereas this is an obligate step for retroviruses.
T or F
HBV cannot be grown in tissue culture
T
HBV cannot be grown in tissue culture.
why is this important
This prevented development of a live attenuated vaccine by passage of the virus in cell culture, and hindered study of virus replication.
describe 4 methods of HBV transmission
info: on HBV: a reversivirus
describe HBVs pathogenesis
give some factors which influence the outcome of HBV infeciton
age
sex
limitations of viral clearance
Males are more likely to develop chronic infection, and therefore HCC, than females.
describe HBV revention
what type of virus is HCV
flavivirus
6 points about the HCV particel
A flavivirus
50 nm diameter
Icosahedral capsid (C protein) Enveloped
Surface glycoproteins E1 and E2.
Genome +ve ssRNA 9.5 kb.
describe HCVs capsid
icosahedral capsid (C protein)
HCVs surface glycoproteins are?
E1 and E2
have vaccines been developed against HCV>
no - because theres such huge diversity
up to 30% nucleotide diversity
describe how HCV replicated
In hepatocytes. New virions are formed by internal budding into the endoplasmic reticulum and are released by exocytosis.
HCV in cell culture was not possible for a long time, but a virus clone that does replicate has been identified and has been invaluable for studying the replication cycle and for testing of anti-viral drugs.
describe HCV pathogenesis
HCV predisposes to what?
Predisposes to liver cirrhosis (10- 20% of cases) in next 30 years
and then Hepatocellular carcinoma (HCC)
HCV prevention and treatment?
Compare HBV and HCV
- HBV:agoodvaccine, but no good drugs
- HCV: no vaccine, but very good drugs
fat
mamba
