Infectious Disease & Pathogenicity 2: Viruses Flashcards
Structure of viruses?
-GM - DNA/RNA
-Protein coat - capsid (ALL)
–> making them - helical/icosahedral…
-Lipid memb - envelope (ALL)
HIV structure?
-Retrovirus
-Enveloped (from host cell)
-ssRNA
-Nucleocapsid
-Capsid
-Matrix
-Recs (host derived) –> gp41 & gp120
What is sense of RNA?
+ve = the strand of RNA can be directly converted to protein (prot biosyn)
-ve = must convert to +ve before get prot biosyn
What is a bacteriophage?
Viruses that infect bacteria - spread pathogenicity genes
How do viruses replicate?
-Infect cell - enter cell, colonise…
-Early enzymes - already in virus - in cell = uncoats virus & involved in early genome rep
-Nucleic acid - prot biosyn (make coat & more) & genome replicates (have many gens)
-Self-assembly = prots adhere (have adhesion points) - will trap nuc acids - euk DNA in some of virus when assembled
-Released = as new virus formed
-Latent period = no viral produced/released
-Then - rapid production/release of virus - all cells infected are at point for this to occur
-Levels off again
–> continual
-Viral rep = step wise process
-Up to 1000 viruses released per infected cell
What are the 3 phases in viral replication?
-Absorption phase (binding & internalisation of virus)
-Eclipse phase (process nuc acids & prot biosyn, genome being replicated)
-Maturation phase (virus formed & released)
DNA based virus replication.
-Recognition, absorption, penetration
-DNA of virus released via uncoating (by early enzymes)
-DNA incorporated into host DNA
-Latent period - rep delay
-DNA replicated - some converted to RNA (RNA polymerase)
-Translation of RNA = proteins for viral formation
-Synthesise viral subunits
-Protease action on polypeptides (proteins)
-Assemble viruses
-Lysis of host cell
-Virus released
-Virus goes to infect more cells
Outcome of viral infection of host cells?
-Release of virus = host cell damage/death
–> via lysis
-Viruses incorporate their genome into host genome –> can become silent (dormant form) for some time
–> stress = re-starts replication
What is viral pathogenesis?
-Process that viral infection leads to disease
-No use to virus
–> virus doesn’t ‘aim’ to kill host
Outcomes of viral infection?
-Acute infection - clearance
-Chronic infection - persistence
What is an acute infection caused by virus?
-Recover w/ no remaining side-effects - or some (neurological deficits)
-Death
-Rapid infection process but will disappear - period of time pre-infection (no symptoms) symptoms for few days then recover
-Can lead to chronic infection
-Are 2 extremes - based on virus
VIRUS WILL CLEAR
What is a chronic infection caused by virus?
-Subclinical infection - low level of viral rep - no real symptoms
-Long dormant phase - once genome of virus incorporated into host genome
–> can be reactivated = acute disease
–> i.e., have relapses & excerbations
-Cancers
VIRUS PERSISTS
Factors - i.e., process of viral pathogenesis (viral infection leading to disease)?
-Viral infection effects cells
-Enters host
-Course of infection - primary rep, systemic spread to other sites of body (MAYBE), secondary rep (dormancy - reactivated - stress = new virus)
-Target specific cell types (a virus’s tropism)
-Cause damage to cells
-Get a host imm resp (unless virus targets imm cells)
-Virus cleared (self-clear due to imm resp) or persists (virus always present where host imm system can’t access)
How do cells respond to viral infection - cellular pathogenesis?
-No change - often latent period - no obvious impact on cell but later could be
-Death - most common - some cell damage
-Transformation
Why do cells die/are damaged by viral infection - DIRECTLY?
–> as virus infects & hijacks cellular machinery
-Divert cell’s energy - to rep viral nuc acids & prots - apoptosis when cell energy levels not at constant level
-Stops cell’s macromolecule syn - viruses divert macromolecule syn from cell prolif (stops cell div) - use cell’s rep (DNA/RNA) machinery for self rep
-Competition of viral mRNA for ribosomes - outcompetes host - so no prots - so damage to remaining prots = induces cell death (apoptosis)
-Competition of viral promoters and transcriptional enhancers for cellular transcriptional factors e.g., as RNA polymerases, and inhibition of the interferon defence mechanisms.
–> makes cell stress - more at risk of lytic death (extreme stress - env of virus lipid from memb - not make enough lipid to maintain - incomplete memb = lysis) & apoptosis
Why do cells die/are damaged by viral infection - INDIRECTLY?
-Integrate viral genome
-Induce mutations in host genome - increased muts in hots genome as rep process taken over by virus - (may reduce proofreading)
-Inflamm - due to lysis/apoptosis of cells & due to PAMPs - virus RNA/DNA
-Host imm resp
Process of HBV infection?
-HBV binds to NTCP rec - is internalised into hepatocyte host (liver) cell - endocytosis
-Virus forms vesicle - interacts w/ lysosomes
-HBV uncoated - then capsid digested by proteases = releases rcDNA
-rcDNA moved to nucleus
-Ligation converts rcDNA into covalently closed circular DNA (cccDNA)
—> gives stable form of HBV so can be persistent
-Can be transmitted to progeny cells (daughter cells from hepatocyte dividing)
-Convert cccDNA into mRNA - transcription (RNA polymerase)
-mRNA into proteins (translation) - prots for capsid, & replicating genome (forms viral/HBV polymerase)
-Reverse transcription - RNA converted to DNA - (genome can come from RNA - more likely to accumulate muts - error prone)
-ve sense DNA syn from RNA (by polymerase activity)
+ve sense DNA syn (from -ve)
2 parts of DNA join = get incomplete ds DNA (not fully match - gap between -ve strand & +ve strand)
-Encapsulate proteins (for capsid or rep of genome)
-Prots for viral env incorporated into viral env in ER - virus buds off from ER
-Virus formed - externalised by ER - viral env made by ER & outer memb
(exocytosis)
General virus disease progression?
-Latency = period between your infection & when you become infectious
-Incubation period = period between are infected & when are symptomatic - so don’t show symptoms yet BUT are infectious!
-Infectiousness = between when start being infectious & when stop (included asymptomatic & symptomatic part)
-Recovery period = live/recover or die
Process of influenza A replication?
-Binds to resp ep cell recs
-Absorbed to resp ep cell - by hemagglutinin spikes
-Fuses w/ memb
-Endocytosis of virus into a vacuole
-Uncoated = releases 8 RNA segments into cytoplasm
-RNA (nucleocapsids) moved to nucleus
-ve sense strand = transcribed to +ve sense strand (uses viral RNA polymerase)
+ve sense strand = translated = viral prots (for capsid & spikes)
+ve sense strand = for glycoprot syn - inserts into memb of host - env forms
+ve sense strand used to syn -ve sense strand
-ve sense strand assembled - put into (nucleo)capsid
-Move (nucleo)capsid to memb (from nuc)
-Mature virus released - exocytosis - buds off - env forms containing spikes (as previously glycoprot spikes inserted into host memb)
Process of COVID replication?
-Binds to ACE2 rec (on MANY cell types - not just resp! - but does have tropism)
-Cleavage of S glycoprot between S1 & S2 (by TMPRSS2)
-Cathepsin route –> cathepsin prots bind to virus = internalises (as cathepsin prots enables memb fusion & release)
—> releases RNA & RNA associated proteins
This is either done by:
1 = pore made in virus - RNA/RNA-assoc prots move into cytoplasm
2 = virus internalised (endocytosis), uncoated due to acidic lysosome env, ssRNA released into cytosol
Replication of genome & translation:
-ve sense RNA converted to +ve (viral polymerase used)
+ve sense RNA translated = viral prots (uses host machinery)
+ve sense used to syn new -ve sense - put into nucleocapsids
-Env glycoprots made (above) - processed in golgi
-Exocytosis after further viral particle assembling
