Trkola - general concepts of tropism and entry.

Question 1

Which factors influence viral tropism?

Answer 1

Entry receptors and cofactors.
Ts.
Environmental instability (pH, proteases)
Host factors
Immunity and restriction factors.

Question 2

Which sialic acid is mostly present in our lungs and in avian targets?

Answer 2

alpha2-3

Question 3

What is the difference between a permissive and a suceptible cell?

Answer 3

A suceptible cell is enabling entry of the virus, but doesn’t necessarily imply it’s permissive.
A permissive cell allows for a full replication cycle.

Question 4

Which are the three conditions for a virus to infect a cell?

Answer 4

It has to be suceptible.
It has to provide the cellular functions required for replication.
Its defense mechanisms are either not present or can be shut down by the virus.

Question 5

What are the three factors defining viral tropism?

Answer 5

Suceptibility, Permissivity, and ability to interact with the tissue.

Question 6

How is Rhinovirus tropism defined in humans?

Answer 6

their temperature sensitivity, allied with a lower concentration of RNaseL in these tissues, make Rhinoviruses tropism favor the URT.

Question 7

What is viremia?

Answer 7

When the virus is detected in the lymph and the blood and can spread either as free particles or as cell-associated entities (ex. migration of infected macrophages).

Question 8

Define pantropicn enterotropic, and neurotropic:

Answer 8

Pan: A virus that can replicate in many different cells and tissue types.
Entero: A virus that can replicate in the gastrointestinal tract. e.g. polio
Neuro: A virus that can replicate in the nervous system. e.g. polio and rabies

Question 9

What special mode of dissemination do certain virus possess?

Answer 9

They can do neuronal spread, taking advantage of the CNS mechanisms of transport. A neuroinvase virus can also cross the blood brain barrier and cause disease there. Examples: rabies, alpha-Herpesviruses.

Question 10

Give all 6 shedding modes for viruses.

Answer 10

• respiratory tract
• Intestinal tract
• Skin (HPV)
• Blood (HIV or Hepatitis)
• Milk (HIV)
• Mucosal secretions (HSV, EBV, HIV).

Question 11

The fuck does nosocomial mean?

Answer 11

Transmission of a virus through a hospital visit.

Question 12

What are the four types of mutations impacting the viral genomes?

Answer 12

Transitions (interchanging of structurally related bases, e.g. A->G)
Transversions: purines to purimidines
insertions and deletions.

Question 13

What’s the genetic variability of viral genomes useful for, and how is it achieved?

Answer 13

Adaptation to the new host and evading immune system or treatments. This can be achieved through mutations, but also recombination and reassortment.

Question 14

How can recombination occur for retroviruses?

Answer 14

Template switch from one strain to another during replication.

Question 15

How can recombination occur for DNA viruses?

Answer 15

recombination through cleavage and ligation between two strains during superinfection.

Question 16

What’s the difference between antigenic drift and antigenic shift?

Answer 16

Antigenic shift = reassortment, drift = accumulation of mutations.

Question 17

what is Cytopathogenesis and Immunopathogenesis?

Answer 17

Cyto: damage to the cells caused by a component of the virus or its propagation.
Immuno: damage of cells through the immune response to the virus.

Question 18

What can a virulence gene do?

Answer 18

Influence viral replication.
modulate host defence.
facilitate viral spread within and between hosts.
Direct toxicity (Rotavirus nsP4 gives you the shits)

Question 19

Besides lytic and non-lytic infections, what’s the third option for a viral infection to cause ?

Answer 19

Syncytium formation by fusing two cells.

Question 20

define genotype.

Answer 20

Virus genus with a specific sequence that can be distinguished from other genotypes.

Question 21

Why is determining genotype of clinical importance sometimes?

Answer 21

In some cases ( e.g. HIV) it can be useful to study the genotype to determine which treatment to use, either regarding resistance or suceptibility.

Question 22

By which two mechanisms can SARS2 enter cells?

Answer 22

Either by receptor-mediated fusion, when TMPRSS2 is present. If it’s absent, then it does receptor-mediated endocytosis.

Question 23

How does SARS2 initiate replication?

Answer 23

Its genomic RNA is positive. The first two orfs, pp1a and pp1b, serve as mRNA to generate the viral RdRp that will replicate the genome.

Question 24

Where does SARS2 replication take place?

Answer 24

In the cytoplasm, in specialised double-membrane vesicles created by the virus.

Question 25

Where are SARS2 virions assembled?

Answer 25

In the ER-Golgi apparatus, in the intermediate compartment. They then discharge by exo cytosis or cell lysis.

Question 26

What's the fastest metholody available to diagnose new virus infections?

Answer 26

Metagenomics.

Question 27

What are the diagnostics tools we have in store?

Answer 27

``` RT-PCR Ab detection Neutralisation assays Viral culture and isolation Sequencing Antigen test ```

Question 28

Is there cross-reactivity between seasonal CoV and SARS2?

Answer 28

Yep a little bit (Ab and T cell).

Question 29

What are the treatments against SARS2 available atm?

Answer 29

Remdesivir ( Monulpavir (nucleoside analog, hypermutations) Recombinant Antibody therapy Serum transfusion

Question 30

Which are the three steps of the entry process?

Answer 30

Attachment, entering, and uncoating.

Question 31

What's the general structure of a Viral Envelope Glycoprotein?

Answer 31

They're integral, containing an ectodomain responsible for the attachment and fusion, and an internal domain required for assembly. These proteins are oligomerics (dimers or trimers).

Question 32

What are the 4 things permitted by the interaction between the virus and the cellular receptor ?

Answer 32

Attachment to suceptible cell Inducing of cell signals to promote entry Inducing structural rearrangements in the virus necessary for entry Inducing structural rearrangements for uncoating.

Question 33

What types of cellular receptors is there?

Answer 33

Porteins, but also macromolecules (lypids, carbohydrates, proteoglycans and glycolypids.).

Question 34

Give an example of a virus needing a co-receptor and its implications.

Answer 34

HIV needs either CCR5 and CXCR4 in addition to CD4 to enter cells: this also defines its tropism between different strains (Transmitter R5 vs IS destroyer X4).

Question 35

What's the fun bit about MeV entry?

Answer 35

It first infects macrophages and DCs using the CD150 receptor then traffics through lymphatic organs while replicating. Finally it spreads to the airway by infecting epithelial cells using the nectin4 receptor for entry.

Question 36

What's the advantage of receptor mediated endocytosis compared to fusion?

Answer 36

The viral proteins don't stay exposed on the cell surface, which means the IS is blind to this means of entry.

Question 37

What's the advantage of fusion compared to RM endocytosis ?

Answer 37

It's two birds, one stone: it enters the virus and uncoats at the same time!

Question 38

Besides endocytosis, how can a naked virus enter the cell ?

Answer 38

It can either expose a hydrophobic moiety to pass through the membrane, or express lytic proteins that will degrade it.

Question 39

How does Adenovirus enter a cell ?

Answer 39

It binds to the CAR receptor, then interacts with integrins that trigger endocytosis and loss of fiber proteins. Then, pH-dependant disassembly begins and AdV leaves the endosome through insert of the hydrophobic protein VI into it.

Question 40

What are the steps for fusion?

Answer 40

Tethering, docking, initiation, hemifusion, pore formation and entry.

Question 41

Wat are the fusion peptides classes:

Answer 41

Class 1: Ebola GP2, HA and gp41 Class 2: Flavi E dimers Class 3: VSV-G Distinguished by main structures (helixes etc).