Viral Replication Flashcards
Different types of replication cycles
Virus infect and then a complete cell cycle occurs releasing progeny virus. Can either lyse the cell (cytolytic and productive) or be noncytolytic and productive usually with persistence of infection
3 distinct phases in normal lytic cycle
Adsorption: virion count begins to drop as virus attaches to cells and initial repl stages begin
Eclipse: no virions as virus penetrates the cell, is uncoated and broken up to unmask the viral genome for viral component synthesis and replication to occur
Assembly and release: large virion number incr
Adsorption and attachment process
Spec parts of virus capsid (capsomeres) or surf glycopros if enveloped recognise spec rec on cell surf
What is a virus rec
A molecule (often a pp) on host cell surf that interacts with a component of the infecting virus in a spec way A pre existing rec with integral role in normal host fx
Rabies rec
Ach rec
Replicates in M cells
ach rec is next to neuromusc jctn
Rabies released and enter neuron via another rec. nucleic acid tracked up neuron to cell body and into brain
Flu rec
Scialic acid
Haemaglutanin binds
Diff shape in diff species chicken straight human bent so cause some species specificity
Influence of rec
Plays a role in disease type and pathogenesis
What cells are infected
Penetration and uncoating: fusion
Only enveloped
Virus mem fuses with CM and necleic acid enters the cell directly
Regulated by spec domains on envelope glycopros
Mem and virus envelope have similar structure
Not all enveloped enter by direct fusion
Penetration and uncoating: endocytosis
Felivers virus to endosomal vesicle with a lower pH than outside the cell Lower pH (higher H+ conc) causes conformational shape change of virus pros req for entry and uncoating (enveloped induce fusion to exit endosome) (nonenveloped exit via conformational revealing hydrophobic fusion peptide (part of a virus capsid pro) that acts to form a pore in the mem)
Fusion peptide action
Run of hydrophobic aas buried in 3D glycopro on virus. Virus bind rec, conformational change, fusion peptide freed, inserts into mem and brings mems together, splits the leaflets and fuses
Why evolved to use endocytosis
Only healthy cells endocytose so virus only enters a cell that can replicate
Endosome trafficks to spec regions
Endosome pumps H+ in so pH down so conformational change induced
Co receptors
Entry and uncoating often req a second or more cell surf molecules as well as the 1o rec (some viruses can have more than 1 1o rec)
If co rec not present then the infection wont proceed or will proceed very slowly
Co rec eg HIV
Bind CD4 but not penetrate, need 2nd rec to induce conformational change for uptake
Class 1 egs
Herpes
Adeno
Pox
Papo
Class 1 replication method
dsDNA (linear or circular) genome
Most (except pox) repl in nucleus and are able to use host mech for transcription. Translation occurs in cytoplasm and then viral pps return to nucleus to finish repl process
Each family has own seq of events but Gen pattern of early pp synth, DNA repl, late pp synth
Only make what they need when they need it
Why poxviridae not repl in nucleus
Very large and encode most of the enz req for repl. Repl in cytoplasm
Early phase v late phase class 1 pp synth
Early: enz req for repl of viral DNA as rare to rely on host enz for this
Higher priority than struct pros (late synth)
Class 2 egs
Parvo
Circo
Class 2 req
Need late s or early G2 to repl so cell must be actively dividing and so they only kill cycling cells which influences the disease
Class 2 repl process
ss DNA
Parvo eg: 2 grps repl autonomously and those that req a helper virus
Rely on cell DNA pol to make ss into ds
Parental DNA strand displaced and more compelmentary to new strand is synthed
Some steps dep on host cell fx only present in late S phase of cell division so autonomously dividing virus req actively dividng cells
mRNA transcribed from appropriate DNA strand and translated normally
Class 3 egs
Reo/rotoviruses
Birna
Class 3 repl process
dsRNA
Repl entirely in cytoplasm
Virus carries its own RNA dep RNA pol which transcribes -ve sense RNA strand to +ve sens mRNA (occurs within capsid)
mRNA extruded into cytoplasm and translated
dsRNA reformed by encapsidation of mRNA and synth -ve sense strand in new capsid
Class 4 egs
Calici Corona Flavi Picorna Toga
Class 4 repl process
+ve sense ssRNA
Genome same sense as mRNA and they code for all their repl fx themselves so genomic RNA infectious on its own
Picornaviridae is most studied and good eg
Picornaviridae repl process (4)
Following cell entry
Entire RNA length translated directly to make large pp pro, then cleaved proteolyticly in stages to yield struct (pps for capsid) and non struct (RNA pol and proteases) pros
RNA pol then use genomic RNA as template for -ve complementary strand synth, which then fx as template for +ve strand synth req for further translation and assembly into progeny viruses
Class 5 egs
Arena Bunya (seg) Filo Orthomyxo (seg) Rhabdo (nonseg) Paramyxo (nonseg)
Class 5 repl process
-ve ssRNA
All carry their own RNA dep RNA pol in virion to enable mRNA transcription
Diff members have diff methods as some have segmented genomes and some don’t (polycistronic)
After entry, viral pol initiates mRNA transcription from genomic RNA (in cell cytoplasm except orthomyxo which does it in nucleus)
Polycistronic genomes make monocistronic mRNAs and small no of polycistronic to be used as template for progeny -ve sense genome
Class 6 egs
Lenti
Retroviruses
Class 6 repl process
Genome +ve ssRNA
RNA dep DNA pol (reverse transcriptase) make cDNA from ssRNA and then as it also has an RNase fx removes original ssRNA leaving single stranded DNA.
Reverse transcriptase can also fx as a DNA pol so makes ssDNA into ds
Dna then integrated into host DNA wear insertion becomes stable and is repl durin normal cell cycle.
Normal RNA pol fron cell then transcr viral mRNA and viral genomic RNA from integrated DNA. Transl of mRNA makes pps to be processed further to produce pros for the virion
Class 7 reversivirus repl process
Hep B
DNA genome repl via RNA intermediate
Genome partially ss and partially ds
dsDNA to ssRNA to ssDNA to dsDNA
Dna virus assembly location
Mainly in the nucleus except pox and irido
RNA virus assembly location
Normally in cytoplasm
Procaspid
Caspid assembly without nicleic acid (as it appears to occur spontaneously) so and empty procaspid
Lipid cell envelope formation
Due to budding through lipid CM
Assembly process
Formation of capsomeres from viral pps that aggregate to form a procaspid
Nucleic acid inserted and may be proteolytic cleavage of some capsid pps
Release process
Naked and the enveloped ones that bud through the internal mems may be released by cell lysis, sometimes released in a less destructive manner via normal cellular transport mechs
Enveloped that bud through CM get released directly
Direct release of enveloped virus
Viral glycopros expressed on cellular plasma mem
Magrix pro binds to plasma men at base of viral glycopro acting as internal marker for ext viral pro presence
Matrix pro has role in organising spatial array of glycopros and acts as site for nucleocaspid to bind
Virus dev by invagination process of modified region of plasma mem causing release of complete virion
Tropisms displayed by viruses
Species
Tissue
Cellular
What determines virus tropism
All life cycle steps
Key: expression of viral rec by host cell and other cell factors altering susceptibility
Parvovirus tropism eg
Repl Req cell fx only in late S or early G2 phases of cell cycle so can only repl in actively dividing cells
How host cells may influence viral repl and vice versa
Action of transacting factors
What may determine virus infection outcome
Differentiation state eg visna virus
Infects macro and mono
In mono growth and repl restricted so accum virus nucleic acid in cell with little viral pp and infectious virus synth
When mature to macro or macro infected de novo the block to virus repl is removed so infection proceed as normal
