Ebola:
The large viral particles attach to the cell surface
They are taken up by a process called macropinocytosis and end up in an endosome
Catapsins (human proteins) cut the glycoprotein and the endosome acidifies (pH drops)
Rearrangement of the glycoprotein allowing interaction with a receptor (NPC1) in the endosome
The virus can escape the endosome and the viral RNA is released into the cytoplasm
The (-) RNA is transcribed into mRNA and these are translated on the ribosomes into proteins
The (-) RNA is also replicated into (+) RNA which serves as a template for more (-) RNA which is incorporated in
new virus particles when they leave the host cell
They leave the cell by budding at the cell membrane
Marburg: see Ebola
Lassa:
The virus attaches to the cell surface by binding a receptor there (αDG)
Once it is in the endosome (and the endosome acidifies causing reorganization of the glycoprotein) it switches to
another receptor (LAMP1) which drives the fusion of the viral membrane with the endosomal membrane
The content of the virus particle is released
You get early transcription and translation (of the L-gene and the nucleoprotein)
Then you get late transcription and translation (of the glycoproteins, matrixproteins and the nucleoprotein)
New virus particles are made
They leave the cell by budding at the cell membrane
SARS-CoV-2:
The spike needs activation first by a human protease (furin) that splits some amino acids.
Then it can attach to the ACE-2 (angiotensine converting enzyme-2) receptor. To be able to fuse, there is a second
activation by TMPRSS2 (transmembrane protease, serine 2) which is also present on the external membrane of
some cells. This entry is called the membrane fusion (happens at neutral pH).
The second way of entering the cell is by endocytosis where you only need the ACE-2 receptor. Inside the cell the
endosomes acidify. There is another human protease (cathepsin L) present in these endosomes which cleaves the
spike proteins and activates the fusion peptide.
After the RNA is “given to” the cytoplasm, the translation takes place on the ribosomes. Only the orf 1 (which
contains the enzymes) is directly translated into proteins.
The polymerase produces an antigenome (negative strand mRNA). From this antigenome you have transcription
the full genomic positive strand RNA and subgenomic mRNA for structural proteins (spike, envelope, membrane,
nucleoprotein) and some non-structural proteins.
Through budding at the ER and further migration to the Golgi apparatus, the full virus is made and liberated as an
enveloped virus.
Dengue:
It starts of course with the entry process. Multiple attachment vectors have been described. The real entry
receptor on cells has not been identified yet.
The virus particle is taken up in an endosome.
These will acidify (the pH will drop) which is a trigger to rearrange the E-proteins of the virus particle (the
organisation of this dimer is rearranged into a trimer). The virus can then escape the endosome.
The (+)ssRNA is immediately translated on the ribosomes and a large polyprotein is produced. This is cleaved into
individual viral proteins to make up virus particles.
They go through a maturation process.
They bud into the endoplasmic reticulum and then follow the Golgi pathway to be released from the cell surface.
For Flaviviruses there is an alternative entry pathway which is antibody dependent. If you have antibodies against
a flavivirus from a previous infection or through vaccination, they can do 2 things. They can neutralise the virus
particle or they can bind the virus particle but not fully neutralize it and actually play against you. The Fc parts can
bind Fcγ receptor on antigen presenting cells, bringing the virus particles in close proximity with these cells. We
thus get antibody dependent uptake of virus particles.
Zika, Yellow fever, West Nile, Japanese encephalitis and Tick-borne encephalitis: see Dengue
The large viral particles attach to the cell surface
They are taken up by a process called macropinocytosis and end up in an endosome
Catapsins (human proteins) cut the glycoprotein and the endosome acidifies (pH drops)
Rearrangement of the glycoprotein allowing interaction with a receptor (NPC1) in the endosome
The virus can escape the endosome and the viral RNA is released into the cytoplasm
The (-) RNA is transcribed into mRNA and these are translated on the ribosomes into proteins
The (-) RNA is also replicated into (+) RNA which serves as a template for more (-) RNA which is incorporated in
new virus particles when they leave the host cell
They leave the cell by budding at the cell membrane
Marburg: see Ebola
Lassa:
The virus attaches to the cell surface by binding a receptor there (αDG)
Once it is in the endosome (and the endosome acidifies causing reorganization of the glycoprotein) it switches to
another receptor (LAMP1) which drives the fusion of the viral membrane with the endosomal membrane
The content of the virus particle is released
You get early transcription and translation (of the L-gene and the nucleoprotein)
Then you get late transcription and translation (of the glycoproteins, matrixproteins and the nucleoprotein)
New virus particles are made
They leave the cell by budding at the cell membrane
SARS-CoV-2:
The spike needs activation first by a human protease (furin) that splits some amino acids.
Then it can attach to the ACE-2 (angiotensine converting enzyme-2) receptor. To be able to fuse, there is a second
activation by TMPRSS2 (transmembrane protease, serine 2) which is also present on the external membrane of
some cells. This entry is called the membrane fusion (happens at neutral pH).
The second way of entering the cell is by endocytosis where you only need the ACE-2 receptor. Inside the cell the
endosomes acidify. There is another human protease (cathepsin L) present in these endosomes which cleaves the
spike proteins and activates the fusion peptide.
After the RNA is “given to” the cytoplasm, the translation takes place on the ribosomes. Only the orf 1 (which
contains the enzymes) is directly translated into proteins.
The polymerase produces an antigenome (negative strand mRNA). From this antigenome you have transcription
the full genomic positive strand RNA and subgenomic mRNA for structural proteins (spike, envelope, membrane,
nucleoprotein) and some non-structural proteins.
Through budding at the ER and further migration to the Golgi apparatus, the full virus is made and liberated as an
enveloped virus.
Dengue:
It starts of course with the entry process. Multiple attachment vectors have been described. The real entry
receptor on cells has not been identified yet.
The virus particle is taken up in an endosome.
These will acidify (the pH will drop) which is a trigger to rearrange the E-proteins of the virus particle (the
organisation of this dimer is rearranged into a trimer). The virus can then escape the endosome.
The (+)ssRNA is immediately translated on the ribosomes and a large polyprotein is produced. This is cleaved into
individual viral proteins to make up virus particles.
They go through a maturation process.
They bud into the endoplasmic reticulum and then follow the Golgi pathway to be released from the cell surface.
For Flaviviruses there is an alternative entry pathway which is antibody dependent. If you have antibodies against
a flavivirus from a previous infection or through vaccination, they can do 2 things. They can neutralise the virus
particle or they can bind the virus particle but not fully neutralize it and actually play against you. The Fc parts can
bind Fcγ receptor on antigen presenting cells, bringing the virus particles in close proximity with these cells. We
thus get antibody dependent uptake of virus particles.
Zika, Yellow fever, West Nile, Japanese encephalitis and Tick-borne encephalitis: see Dengue
