Pathogens II Flashcards
How viruses enter cells - integral membrane proteins
Integral membrane proteins in envelopes of the enveloped viruses drive fusion with pm of target cells
How viruses enter cells - In some cases
The fusion with pm of target cells = involves immediate fusion with cell surface (hiv, measles)
How viruses enter cells - Common way of fusion
For enveloped viruses to only fuse with pm after exposure to low ph in endosomes - usually early endosomes
How viruses enter cells -Non enveloped viruses
Must usually disrupt endosome membrane to get their nucleic acid into the cytoplasm
How viruses enter cells - Enveloped ex image
HIV - aids = fusion with membrane
How viruses enter cells - Non evenloped ex image
Endocytosis
Inject nucleic acid directly or by break open lysosome
Name picornaviruses
Poliovirus
Rhino virus - do not replicate well at 37 degrees
Norovirus
Describe picornaviruses - ex
Endocytosis
Proteolytic processing
Genome replication - replication organelle
Virus particles assemble n cytoplasm
Then lytic release = get into cytoplasm
What happens when picornaviruses in endosome
Once in endosome = exposed to low ph
= inject rna genome into cytoplasm
picornaviruses = after endosome, describe their genome
Genome can function directly as a messenger rna, leading to synthesis of first virtual proteins including rna directed rna polymerase
picornaviruses = descrive what they do - after in endosome specifically
Rna genome threaded through wall of endosome and goes into cytoplasm
—> pore formation, genome release - virtual replciation
Describe replication organelle - picornaviruses
Arise from er membranes
Also - especially for poliovirus = virus modifies ribosome so it will recognize viral rna more = so cell with produce more viral rnas = boost virus replciation
What is propose of replciation organelle - picornaviruses
Replication in secluded area helps virus avoid detection by host cells
Prevent autophagy/apoptosis and antiviral measures
Describe picornaviruses - ps vesicles
Phosphotidyl serine rich surrounds autophagsome (maybe, looks like autophagosome but not sure)
Then fuse with cell surface
—> endocytosis by next cell = get many viral rna genomes = speeds up infection process
picornaviruses- late endosome
Can sometimes fuse with pm then release internal vesicles = exosomes
picornavirus life cycle = binds
Virus binds receptor on cell surface and is endocytosed
picornavirus life cycle = after endocytosis
= exposed to low endosomal ph
Viral rna is threaded through a pore made in endosomal membrane by a viral protein (vp4)
picornavirus life cycle = rna
The rna fed through pore = binds ribosomes and is translated, producing viral proteins, including rna directed rna poly
picornavirus life cycle = once viral replciation
Once viral rep begins = viral replciation organelles created that are associated with er membranes - modify er membranes
= viral particles - assembled in cytoplasm, do not actually have membrane
picornavirus life cycle = ribosomes
Modificed so that they preferentially translate viral mRNA
Most translation of cellular proteins stops - eventually leads to death host cell
picornavirus life cycle = viral structure proteins
Vp1, vp2, vp3 (viral protein) associate with viral rna in cytoplasm to form virus particles
Particles can be released when cell dies
picornavirus life cycle = process
Process where multiple virus particles are enclosed in a phosphoserine rich membrane
picornavirus life cycle = phosphoserine rich membrane
Phosphoserine rich membrane is itself enclosed in an autophagosome like structure, which fused with pm
Releasing phosphoserine rich vesicle while infected cell still alive
Vesicles can be endocytosed by adjacent cell = resulting in its infection
(Recall = non envelope virus)
Describe how sars cov 2 can enter cells - Gen
SARS cov 2 can enter plasma cells directly at pm (at cell surface, binds ace2r) or by fusion with endosomal membrane depending on variant!!!
Describe how sars cov 2 can enter cells - specifically fusion of membranes
Spike protein undergoes conformational change = exposes hydrophobic areas =destabilize area they are bound to = leads to membrane fusion
Also have rna that is directly recognizable that has ribosome binding sites = can get everything going
Describe how sars cov 2 can enter cells - spike protein
Spike protein on a virus particle binds to ace2 receptor at cell surface
Describe how sars cov 2 can enter cells - conformational Change
Conformational change in spike protein = causes virus envelope to fuse with cells membrane
Depends on variation =virus may fuse directly at cell surface (delta) or be endocytosed and fuse with endosomal membrane (omicron, for most variants)
Describe how sars cov 2 can enter cells - fusion results
Fusion results in entry of entire nucelocapsid including viral rna into cytoplasm
Genome of sars cov 2 virus can bind directly to a ribosome and be translated
How does hiv enter cell - enveloped vrisues
The env protein complex of hiv binds cd4 protein on surface of T cells
And virus fuses directly with pm
How does infleunza enter cell - enveloped vrisues
Ha protein of influenza virus binds to sialic acids on N-glycosylations of cell surface proteins
Virus then endocytsoed and a ph induced (low ph) conformational change in HA leads to fusion with endosomal membrane
Describe SARS cov 2 virus factories
Produces proteins that insert into er membrane and modify them
Integral membrane protein nsp6 = forms highly tabulated er membranes = dsdna hides in crevices = cell unlikely to detect it until too late
What does sars cov 2 do to er membranes
Recognizes er membranes to Shield viral rna during replication
= internal shielded space where viral dna replicates
multiple genomes - starts to produce viral structure protein - introduced into er with translocation apparatus - early infection - go to golgi/internal membranes
Describe ex of enveloped virus budding - integral membrane proteins
Integral membrane proteins found in virus envelope must use secretory pathway to reach destination where virus budding occurs
- usually (but not always) cell surface (ex - semliki forest virus)
Describe ex of enveloped virus budding - process
Capsid binds to e1e2 = protein at cell surface
Envelope proteins - synthesized in er —> golgi —> cell surface, reg secretory pathway
Describe ex of enveloped virus budding - image
Nucelocapsid induced assembly of evenlope proteins - upon signal
Then budding = can see in em
Budding of many enveloped viruses is very simple - nucleocapsid
Nucelocapsid composed of proteins associated with viral nucleic acids (rna/dna depending on virus)
= assembles in cytoplasm
Budding of many enveloped viruses is very simple - meanwhile
One or more viral integral membrane envelope proteins synthesized and translocated to er
- then traverse secretory Pathway normally and reach cell surface
Budding of many enveloped viruses is very simple - viral nucleocapsid
Binds to cytoplasmic domains of envelope proteins at cell surface - this interaction leads to budding
Is sars cov 2 a simple one
NAHHHH
Ex enveloped virus = sars cov 2 = gen
VIRAL envelope proteins found in Vtcs
Then viral nucleocapsid bind and viral particles bind into vtcs
Ex enveloped virus = sars cov 2 = theory 1
NOT SUPER CLEAR
Can find protein in golgi —> but after certain time in infection = do not have Golgi - cannot recognize morphologically = so cannot track
Ex enveloped virus = sars cov 2 = theory 2
Maybe =
SARS cov 2 = reported to bud into lysosomes, lysosomal ph = also modified to be less acid - so that lysosomal enzymes inactive, ion channel encoded by virus maybe be responsible for deacidifying endosomes (e protein)
Means that envelop proteins of sars cov 2 (spike and 3 smaller proteins) must be targeted to enodosome/lysosome system
Not worked how these proteins targeted here
Ex enveloped virus = sars cov 2 = theory 2 E protein specifically
Ion change
Accumulates in lysosomal membrane and renders it neutral = so lysosome neutral ph = harmless to virus
Then fuses with pm and releases vrisues out
How does sars cov 2 bud
Buds into multiple intracellualr membranes - including Ergic and vtcs
Describe sars cov 2 Virus particles
Virus particles may traverse Golgi - however = what happens in cell not clear
And Golgi highly disrupted during infection
Evidence for sars cov 2 - lysosome
Evidence that viral particles end up in lysosomes
One of envelope proteins - E acts as ion channel, collapsing ph gradient and deacidifying lysosome
Lysosome then fused with pm = releasing virus particles
sars cov 2- what is exact story
Exact story not universally accepted
Internal membranes are highly disrupted= making identification of organelles difficult
Something along these lines happens (recall- lysosome evidence)
sars cov 2 - if get diff variant
Still abs kinda effective
Helps lessen symptoms
