viral entry Flashcards
what is viral entry (what does it consist of)?
recognition of the host receptor (attachment) and a mechanism to release the genome into the cell!
why can’t viruses passively diffuse thru the host cell membrane?
viruses may be smaller than ribosomes, but they are much larger than small molecules (such as Na+) that they cannot be passively transported thru the host cell membrane
they require channels on the host cell – made by the virus!
describe the stability of the viral particle as it enters the host cell
the virus must be stable when it first enters as it holds onto its structure and genome, but after entry, it can become unstable to release the genome
how is attachment initiated?
random electrostatic interactions (random collision events) do occur between virions and receptors but they do not initiate the infectious cycle
due to the degree of specificity of the virion, there must be a specific interaction between the virus and the receptor that will initiate the infectious cycle - this determines the virus’ host range
in most cases, a virus requires a second-receptor, the “co-receptor” – excluding viruses that infect yeast and plants
which viruses do not require host receptors?
viruses that infect yeast and plants
what receptors does HIV use?
HIV can recognize CD4 and chemokine receptors (CC and CXC)
what receptors does poliovirus use?
polio can recognize PVR (poliovirus receptor)
what receptors does rhinovirus use? and what role does this receptor normally perform in the cell?
rhinovirus can recognize LDL-receptors, which is also used to regulate lipid metabolism in humans
what is rhinovirus?
causes the common cold
what receptor does measles virus use? and what role does this receptor normally perform in a cell?
measles virus can recognize CD46, which plays a role in human reproduction and in the immune system
what receptor does SARS-CoV-2 use? and what role does this receptor normally perform in a cell?
SARS-CoV2 can recognize angiotensin-converting enzyme 2 receptor (ACE2), which is also used to regulate parts of the cardiac metabolism
how does a non-enveloped virus attach to viral receptors? using the example poliovirus
poliovirus has 3 types proteins which forms the compact triangles on the surface - 60 faces of 3 viral proteins each
- 60 VP1 (membrane insertion, forms the canyons)
- 60 VP2
- 60 VP3
the poliovirus will inject RNA directly across the plasma membrane after a conformational change in capsid proteins
2 VP1 from the virion will interact with a receptor, in this case PVR – then, the hydrophobic N-termini of VP1 will insert into the membrane creating that channel for genome insertion
- in this process VP4 is buried between the membrane and VP1
these can all be described as conformation changes in capsid proteins – viral genome injection occurs after
describe poliovirus (details!) and then it’s arrangement of proteins
poliovirus in the family: picornaviridae “small RNA virus family”
+ssRNA, thus, doesn’t require modification to be read by host ribosome
poliovirus has icosahedral symmetry. it has 3 types proteins which forms the compact triangles on the surface - 60 faces of 3 proteins each
- 60 VP1 (membrane insertion, forms the canyons)
- 60 VP2
- 60 VP3
how does an enveloped virus attach to viral receptors? using the example influenza…
hemagglutinin is glycoprotein found embedded in viral envelopes
hemagglutinin will bind to the host’s receptor, Sialic Acid, a sugar
sialic acid is almost always linked to a galactose molecule in either a 2-3 linkage or a 2-6 linkage
2-3 linkage: 2-C of sialic acid and 3-C of galactose
2-6 linkage: 2-C of sialic acid and 6-C of galactose
avian influenza viruses preferentially prefers 2-3 linkages
human influenza viruses have evolved to preferentially prefer 2-6 linkages
but we also have 2-3 linkages! just in our lower tract… so we can be affected by avian influenza viruses
variability in linkages determines what virus gets in and where - location is key!
sialic acid receptors with 2-6 linkages in upper and lower tract will bind human influenza viruses
sialic acid receptors with 2-3 linkages in lower tract (lungs) will bind avian influenza viruses
because of location, symptoms take longer to appear as viruses must travel a longer length; also, very deep breath of many virions are required to make this possible
what type of genome does influenza have
-ssRNA
why did COVID-19 originally require 2 weeks isolation but now doesn’t require a long period of isolation? and why was it less infectious before?
during early COVID times, infections were more rare and required longer isolation periods… because of the variability in ACE-2 receptors that SAR-CoV2 bonded to
SARS-Cov2 preferentially binds to ACE-2 found in the lower respiratory tract (aka lungs and this is more dangerous)
- it would take a while for symptoms to appear from the replication of viruses
as omicron, the evolved virus, came out, it could now preferentially bind to ACE-2 receptors in the upper tract
the virus became more contagious – it could just bind to the nose – and now not as capable of making it to the lungs, thus, less severe
human immune system is more effective in eliminating viruses in the upper tract
what are the mechanisms to release viral particles into the cell?
viruses enter the cell via common cellular mechanisms of endocytosis - invagination
receptor-mediated endocytosis (main method)
phagocytosis “cell-eating”
pinocytosis “cell-drinking”
transport vesicles move along track that are powered by molecular motors of the host – this is how viruses are moved inside the cell
a trigger will release virus/genomic contents in the cytoplasm
what are the different locations of genomic release and what differentiates these locations?
release can occur right at the cell surface (e.g. in bacteriophage)
pH = 7
release can occur at an early endosome
pH = 6.5-6
release can occur at a late endosome
pH = 5.5-5
note that the acidity increases as we go further in the cell
describe the release of genome for a reovirus, a non-enveloped virus
can use multiple receptors
the pH at the early endosome causes loss of capsid
the pH at the late endosome results in holes being created in the late endosome
– caused by low pH AND cysteine proteases (aka cathepsins) from the host – this promotes release of genome
what viruses will release their genomes at the plasma membrane
this is true for some enveloped viruses
the fusion events of the lipid-bilayers are regulated
the viral fusion proteins will behave differently depending on the specific pH
e.g. measles virus, an envelope virus of the paramyxoviridae family
what family does measles belong to?
paramyxoviridae
