Virus Entry Flashcards
What are the 2 problems viruses need to solve in order to enter a cell?
1 - find the right cell
2 - penetrate plasma membrane to enter cell
What is the 3 stage process for viruses to deliver genomes into cells?
Attachment
Penetration
Uncoating
What are the 3 things involved in virus attachment?
Attachment factors
Virus receptors on cell surface
Cell tropism - determinant of disease causes and pathogenesis
What are features of virus attachment factors
Glycosaminoglycans (GAGs) Linear polysaccharides Unlinked/linked to surface proteins Neg charged bind viruses electrostatically
What is an example of virus receptors?
HRV14/16 - ICAM-1
HRV2 - LDLR
receptors have a normal function in the cell
How does HRV bind to the receptor?
receptor binding site at base of canyon
ICAM-1 can reach - antibodies cannot
What are HIV receptors?
Primary receptor - CD4 - normally binds to class II MHC on APCs
Chemokine receptors - 7TM helices - normally bind chemokines
What do HIV glycoproteins do?
multimerise to form spikes
surface protein - gp120
transmembrane protein - gp41
V3 variable tip
How do HIV receptor interactions occur?
gp 120 - neg charged GAGs on CD4
V3 loops interacts with 2nd receptor - chemokine recepro
How can receptors determine disease progression & pathogenesis?
V3 loop mutation - acidic to basic
change ability to infect certain cells
How can HIV infect different types of cells over time?
early - infect macrophages expressing CCR5
later - infect T cells expressing CxCR4
How can virus entry be targeted for HIV therapy?
Maraviroc - CCR5 antagonist - keeps virus at a low level and in the asymptomatic phase
What are influenza glycoproteins?
HA trimer gets cleaved into HA1 and HA2
HA binds to sialic acid
How does sialic acid linkage determines the host range of influenza?
Avian HA - 2,3 linkage to galactose
Human HA - 2,6 linkage to galactose
single mutation can change tropism
what is SARS-CoV-2 glycoproteins?
Spike glycoprotein trimer
cleaved into S1, S2
S1 contains receptor binding domain (RBD)
What is the receptor of SARS-CoV-2?
ACE-2
normal role in blood pressure & inflammation
cleaves angiotensin into Ang(1-9)
TMPRSS2 cleaves S protein to activate
How do bacteriophages penetrate the bacterial cell?
punch hole through wall to deliver genome
What is the cortical cytoskeleton?
cluster of actin and tubulin fibres - give integrity
What are the 3 mechanisms of endocytosis?
1 - Clathrin mediated endocytosis
2 - Non-clathrin dependent
3 - Macropinocytosis
What happens during clathrin mediated endocytosis?
clathrin cage membrane curvature pinched off vesicle targeted to endosomes acidification
What happens during non-clathrin dependent endocytosis?
caveolae formed from cholesterol rich lipid rafts
Targeted to ER
bunyaviruses
What happens during macropinocytosis?
membrane ruffling
large vesicles
used by large viruses e.g. herpes
How does influenza virus get into cytoplas?
drop to acidic pH in endosome
induces fusion of virus and membrane
capsid releases virus into cytoplasm
How does HIV get into the cytoplasm?
fusion of viral and plasma membranes
release capsid into cytoplasm
How can fusion of the virus and the membrane occur?
fusion peptide - short hydrophobic amino cid sequence
What can trigger the fusion peptide to be exposed?
- low pH - influenza
- binding to co-receptor - HIV
- after cleavage - SARS-CoV-2
- high K+ conc - Bunyavirus
How do intramolecular interactions force membranes together
fusion peptides originally hidden now stick out
interact with plasma membrane
glycoproteins contract to squeeze 2 membranes together
What are the 3 ways a non-enveloped virus can enter the cytoplasm?
1 - uncoating before endosome disruption
2 - endosome disruption before uncoating
3 - pore formation
What is virus uncoating and what triggers it?
exposure of genome for replication/translation
pH
Acidification
How does mimivirus uncoat?
stargate opens up to release genome
How does Influenza enter the nucleus?
transport of uncoated virus material
RNP complexes attch to nuclear protein
How does HIV enter the nucleus?
reverse transcription with partially uncoated capsid
How does herpes virus enter the nucleus?
taken along down microtubules
uncoating at nuclear pore - DNA inserted with associated proteins
