Lec 5: Attachment & Entry Flashcards
general the process of virus replication: (7)
(AETTGAE):
- Attachment of a virion to a cell
- Entry into the cell
- Transcription of virus genes into messenger RNA molecules (mRNAs)
- Translation of virus mRNAs into virus proteins
- Genome replication
- Assembly of proteins and genomes into virions
- Exit of the virions from the cell.
Not all of the seven steps… (2)
- are relevant to all viruses,
- depending on type of genetic info they are (+/-)
- occur in the same order, and some have an additional step
attachment and entry of viruses into cells; mainly on the mechanisms used by
animal viruses
Receptors and co-receptors are…
that include… (2)
…cell surface molecules, usually glycoproteins, with a wide range of functions that include:
- acting as receptors for chemokines and growth factors;(chemokines, small proteins guide the migration of cells)
- mediating cell-to-cell contact and adhesion
The recognition of a receptor by a virion is
highly specific
Sometimes a second type of…
…cell surface molecule (a co-receptor) is needed in order for virus to infect a cell.
The virus-receptor binding causes a…
…conformational change in the virus protein that enables it to bind to the co-receptor
for attachment, what is more important? (DNA or protein)
protein!
- Protein binding = conformational change
- Diff protein structure = completely different action
How to prove a receptor is a virus binding cell surface protein? (4)
- mAb (monoclonal antibody)
- Soluble derivatives of the molecule block virus binding/infectivity.
- The normal ligand for the molecule blocks virus binding/infectivity.
- Introduction of the gene encoding the molecule into virus-resistant cells, and expression of that gene, makes those cells susceptible to infection.
Monoclonal antibody (mAb) recognizes:
single epitope
Polyclonal antibody (pAb) recognizes:
multiple epitopes
epitope =
part of antigen that’s recognized by immune system antibodies, B-cells, or T-cells
B cells =
makes antibody
epitope aka
“antigenic determinant”
mAb can help determine
viral specificity
Ab can bind to
virus surface receptor and block viral binding to cell
Drugs can bind to
virus AND cell to block viral binding
- however, virus surface protein is more likely to undergo mutation quicker than cell, t.f. its more efficient to design a drug that would bind to the cell instead of the virus
(animal viruses)
Each virion has
multiple sites that can bind to receptors
(animal viruses)
Each site is made up of
regions of one or more protein molecules
(animal viruses)
The virus attachment sites of naked viruses are on
- sometimes… (2)
the capsid surface (ex: picornaviruses)
- sometimes within depressions (poliovirus)
- sometimes on ridges (ex: foot & mouth disease)
Binding to receptors induces…
major structural changes in the virion
(virus attachment sites within depressions)
canyons on the virion surface, virus attachment sites located in…
…pockets at the canyon bases.
- The canyons are too narrow for access by antibodies — the virus attachment sites are protected from the host’s immune surveillance
Some virion surface proteins that bear the virus attachment sites are able to…
bind strongly to red blood cells of various species and cause them to clump, a phenomenon known as haemagglutination.
haemagglutinins =
The viral proteins responsible for haemagglutination
What causes the binding of a virus attachment site to a receptor? (3)
- hydrogen bonds,
- ionic attractions and
- van der Waals forces (No covalent bonds)
(Attachment of virions to receptors)
- Initially, a virion is…
- more…
- …weakly bound to a cell at only one or a few receptors = reversible attachment
- …virus attachment sites to bind to more receptors = irreversible.
Entry of animal viruses into cells: (2)
- may enter either at the cell surface (fuse directly with the plasma membrane)
- may cross the endosomal membrane
Some enveloped viruses require…
So, endoscope provides…
an acidic pH for fusion to occur and are unable to fuse directly with the plasma membrane.
- Endosome provides the acid environment.
Entry of NAKED viruses into cells: (2)
- through a pore in the plasma membrane
OR - endocytosis (more common)
Entry of ENVELOPED viruses into cells: (2)
- by membrane fusion at the cell surface AND by endocytosis,
OR - ONLY by endocytosis
(Intracellular transport)
Once in the cell, the virus (or its genome) may have to be…
- Most RNA viruses…
- Retroviruses, also RNA viruses…
- Most DNA viruses…
…delivered to a particular location, such as the nucleus.
- …replicate in cytoplasm (flu virus exemption)
- …need nucleus
- …need nucleus with a few exemptions
motor proteins: (2)
kinesin = draws cargo to + side dyne = draws cargo to - side
Genome uncoating =
The complete or partial removal of the capsid to release the virus genome.
Genome uncoating can take place: (4)
- at the cell surface, (the capsid remaining on the exterior surface of the cell)
- within the cytoplasm
- at a nuclear pore
- within the nucleus
successful entry of a virion into a cell is not always
followed by virus replication
The host’s intracellular defenses (such as lysosomal enzymes) may…
In some cases the virus genome may…
…inactivate infectivity before or after uncoating
…initiate a latent infection rather than a complete replication cycle
Like animal viruses, phages bind specifically to
receptors and coreceptors
On the cell side, some of the molecules are on…
On phage sides, many of the virus attachment sites are on…
…the surface of the host cell wall, some are on the surface of other structures (pili, flagella or capsules).
…particular virion structures, such as the tail fibres of phage T4.
For most animal and plant viruses…
the entire virion (or at least the nucleocapsid) enters the host cell.
