DNA Viruses Flashcards
Outline the 10 steps of DNA virus replication
- Attachment or adsorption
- Penetration
- Uncoating of virus & transport of genome to site of replication
- Early Transcription (mRNA)
- Early translation & early viral protein production
- Viral DNA synthesis
- Late transcription of further mRNA
- Late translation & synthesis of structural proteins
- Assembly
- Release
*If one step blocked then the other steps in replication process are also blocked
Describe the one step Growth Curve
- Viral attachment and penetration into cells
- shortly after infection - only low amounts of parental infectious virus identified
- Eclipse phase: virus replicates inside cells (but progeny virus not yet produced (seen as a plateau)
- Mature infectious progeny virions released = exponential phase (released into surrounding medium)
- after few hours cells infected become metabolically disordered and virus production ceases (plateau)
Step 1: Attachment
-neutralisation
- AKA adsorption
- virus attaches via surface protein and a complementary protein (receptor) on the surface of the cell
- occurs after random collision between virus and cell bearing right receptor
- Most of virus attaches in short period of time (mins), more time needed for residual virions to attach (hours)
- Viral attachment protein on surface of protein coat or inserted into envelope
- if antibody present - attaches to viral attachment protein and prevents virus from attaching to appropriate receptor = NEUTRALISATION
- right receptors not present on all cells - means cells exhibit tropism
- cellular receptor site usu. a glycoprotein
Step 2: Penetration
-2 ways;
-Fusion of envelop of virus w/ plasma membrane & direct release of nucleocapsid into cytoplasm [mediated by specific proteins or glyoproteins]
OR
-Engulfment of virus by cell in adsorptive endocytosis before the viral nuclei acid genome is released.
Step 3: Uncoating
Methods for;
- Poxvirus
- Herpesvirus
- Circovirus
-refers to freeing the viral genome
-occur in cytoplasm or in nucleus (where most DNA viruses replicate)
DIFF VIRUSES HAVE DIFF STRATEGIES:
-Poxvirus: replicate in cytoplasm - host factors induce disruption of virus core to release DNA
-Herpesvirus - replicate in nucleus - nucleocapsid migrates to cell nucleus via microtubules to nuclear pore and virus genomes released into nucleus
-Circoviruses replicate in nucleus - gain entry to nucleus during mitosis (Need cell division for replication to occur)
Step 4 & 5: Early transcription & translation of viral proteins
- Where these processes occur
- Early coded proteins
- formation of mRNA from virus DNA & early viral-coded proteins (translation)
- Most transcriptional events occur in nucleus - mRNA transported to cytoplasm where translation of coded proteins occurs using host cell ribosomes.
- proteins transported back to nucles where they are need before more steps can occur
- early coded proteins = enzymes necessary for DNA synthesis
- early transcription stops when viral DNA synthesis begins
Step 6: Viral DNA Synthesis
-e.g. of ones that use own polymerase & those that hijack cell’s polymerase
- Viral DNA synthesised to progeny viral DNA
- Some DNA virus families encode a DNA-dependent DNA polymerase (i.e. Herpesviridae, adenoviridae, poxviridae)
- Others rely on host cell’s DNA-dependent DNA polymerase (i.e. circoviridae, parvoviridae, polymaviridae, papillomaviridae)
Step 7 & 8: Late transcription and Translation
- Late transcriptional events occur AFTER DNA synthesis has occurred
- late mRNAs transported to cytopalsm for translation into structural proteins by host ribosomes
- May be translated as polyproteins & need to be cleaved by proteases
- May be glycoslated w/in trans-Golgi network
Step 9: Assembly of Virions
- Proteins & synthesized viral DNA packaged together = progeny virus
- inner core created first (ass. w/ DNA), capsid proteins last.
- Most DNA viruses assembled in nucleus
- Poxvirus: protein and DNA accumulate in common cytoplasm virus factory (inclusion body)
- Assembly occurs after structural proteins migrate back to nucleus where DNA replication & transcription have occurred
Step 10: Release of Viral Particles
-2 ways
2 ways to occur:
- Autolysis of cell: used by most DNA viruses (virus induced apoptosis may be involved)
- Herpesvirus mature by more complex process during which the viruses acquire an envelope and endocytosise out of cell
Parvoviruses;-
Genome virion enveloped replication target fragility host range
- 5kb, (-) single-stranded, linear DNA
- Icosahedral, 18-26 nm diameter
- No
- Intracellular
- Rapidly dividing cells
- V. resistant in enviro.
- Arthropods and mammals
Parvovirus - DNA in more detail
- Has hairpin (palindromic) structure at 3’ end - used as self-primer to start syn. of plus sense DNA (ss loop back on themselves) [unique to this family]
- dependent on cell division for replication (initiates division after host cell has completed S phase [uses cellular polymerases available in early G phase]
- replicate in nucleus - often producing intranuclear inclusions
Parvovirus: autonomous viruses & defective virus replication
-survival in enviro
Autonomous: need cells to pass through S-phase
Defective: require host machinery PLUS helper virus for replication (called dependoviruses - can’t replicate on own are not considered pathogenic)
-Very stable in enviro - survive pH 3-9 & at high temps
-susceptible to formaldehyde and chloramines and bleach
(though appropriate contact time necessary for inactivation)
-typically results in cell death (necrosis is common feature)
Parvovirus: Pathogenesis (where they infect)
*cells w/ high turnover rates, e.g.
- actively dividing cells in villi of intestine
- lymphoid tissue and bone marrow
- virus affects actively dividing Purkinje & cerebellar cortical cells in brain
Human Parvovirus (B19 Virus)
- major, medically relevant human parvovirus
- spread via respiratory route
- approx. 60% adults seropositive
- replicates in erythroid progenitor cells (found in bone marrow)
- results in rash & arthraligia/arthritis
*called B19 = blood sample no. that was first found to have virus in Australia
