viral entry

Question 1

what is viral entry (what does it consist of)?

Answer 1

recognition of the host receptor (attachment) and a mechanism to release the genome into the cell!

Question 2

why can’t viruses passively diffuse thru the host cell membrane?

Answer 2

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!

Question 3

describe the stability of the viral particle as it enters the host cell

Answer 3

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

Question 4

how is attachment initiated?

Answer 4

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

Question 5

which viruses do not require host receptors?

Answer 5

viruses that infect yeast and plants

Question 6

what receptors does HIV use?

Answer 6

HIV can recognize CD4 and chemokine receptors (CC and CXC)

Question 7

what receptors does poliovirus use?

Answer 7

polio can recognize PVR (poliovirus receptor)

Question 8

what receptors does rhinovirus use? and what role does this receptor normally perform in the cell?

Answer 8

rhinovirus can recognize LDL-receptors, which is also used to regulate lipid metabolism in humans

Question 9

what is rhinovirus?

Answer 9

causes the common cold

Question 10

what receptor does measles virus use? and what role does this receptor normally perform in a cell?

Answer 10

measles virus can recognize CD46, which plays a role in human reproduction and in the immune system

Question 11

what receptor does SARS-CoV-2 use? and what role does this receptor normally perform in a cell?

Answer 11

SARS-CoV2 can recognize angiotensin-converting enzyme 2 receptor (ACE2), which is also used to regulate parts of the cardiac metabolism

Question 12

how does a non-enveloped virus attach to viral receptors? using the example poliovirus

Answer 12

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

Question 13

describe poliovirus (details!) and then it’s arrangement of proteins

Answer 13

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

Question 14

how does an enveloped virus attach to viral receptors? using the example influenza…

Answer 14

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

Question 15

what type of genome does influenza have

Answer 15

-ssRNA

Question 16

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?

Answer 16

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

Question 17

what are the mechanisms to release viral particles into the cell?

Answer 17

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

Question 18

what are the different locations of genomic release and what differentiates these locations?

Answer 18

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

Question 19

describe the release of genome for a reovirus, a non-enveloped virus

Answer 19

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

Question 20

what viruses will release their genomes at the plasma membrane

Answer 20

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

Question 21

what family does measles belong to?

Answer 21

paramyxoviridae