Karteikarten
Week 8 Viruses
Karten in diesem Stapel (47)
- 1Virus structureEnveloped - easily destroyed
non-enveloped - robust and stable - 2Componetns of virionsEnvelope - host derived lipid membrane containing viral derived proteins
Tegument - amorphous protein layer (Herpes)/matrix
Capsid - outer protectives protein coat
Nucleocapsid - inner protectivve protein coat
Genome/nucleic acid
Accessory proteins
Outer protective layer that mediates binding and entry of virion
Nucleic acid/genome - 3Classification of virusesThe way they look under EM
Diseases they cause
way they are transmitted
Do not reflect genetic relatedness - 4Baltimore classification of virusesDevised by David Baltimore
Based on kind of genetic material in virus
mRNA as central component of all life
DNA --> RNA --> mRNA --> proteins--> Function - 5Generalities about viral geneticsCompact
very little non-coding space
Overlapping reading frame
Translational read through
Alternative splicing
Co-ordinated expression - 6Generic viral replication cycleBinding and entry
Genome replication
Viral mRNA transcription and protein translation
Assembly and release - 7Attachment Viral replication cycleAttachment proteins on surface of viruses bind got specific receptors on surface of animal cells (glycoproteins or glycolipids)
Interaction between attachment proteins and receptors is determinant of host-range - 8Penetration virus replication cycleOnce bound to cell membrane, virus or at least its nucleic acid must enter the cell
endocytosis: enter via receptor mediated endocytosis
Virus binds to receptors at coated pits - coated pits pinch off to form coated vesicles
Endosomes become more acidic
Viral genomes must escape
Enveloped virus, occurs by membrane fusion mediated by fusion protein e.g. HA protein - 9Uncoating and targetingGenome is released from capsid during or after penetration (uncoating)
Capsids undergone some conformational changes during infection that allows viral gene expression or replication to begin - 10Gene expression and replication Virus replication cycleVirion components (proteins) must be produced
Viruses with DNA genomes: DNA viruses have genomes similar to host cell. DNA viruses replicate in cell nucleus
Viruses with RNA genomes: Most replicate in cytoplasm of infected cells. High levels of recombination - 11Virus assembly and releaseNew viral genomes have been produced they are assembled into new viriosn
Viral capsid is partially assembled - 12Hepatitis B virusorthohepadnavirus
Hepadnaviridae family of virus
Consists of outer lipid envelope and nucleocapsid core composed of protein
Nucleocapsid encloses viral DNA and DNA polymerase - reverse transcriptase activity
Genome of HBV is made of circular double stranded DNA - 13Vaccinia virusBinding and entry
mRNA production and protein translation
Genome replication
mRNA production and protein translation
Assembly and release - 14Flavivirus Life CycleBinding and entry
mRNA production and protein translation
Genome replication
mRNA production and protein translation
Assembly and release - 15Viral replication Binding and entryVirus entry
- receptor mediated
- specific receptor
- multiple receptors
- non specific binding e.g. glycans
- non receptor mediated e.g. phagocytosis or direct
Target cell determined by
- entry - presence of receptors or mechanisms for uptake
- post entry replication determinants - 16Target cells and entry mechanismsHIV - receptor mediated surface fusion and/or phagocytosis
CD4+ T cells, Monocytes/macrophages/dendritic cells
CD4+ chemokine co-receptor (CCR5, CXCR4)
Hepatitis C - receptor-mediated endocytosis.
Influenza - receptor mediated endocytosis - 17Cell target can determine dsieaseReceptor usage determines site of infection and disease outcome
Examples: HIV
CCR5: macrophage tropic, slow, non-cytolytic infection (early stage disease)
CXCR4 = T cell, rapid, cytolytic infection - 18Viral genome replicationCan be complex, virus specific, cytoplasmic or nuclear
Virus has its own polymerase
DNA virus - DNA dependent DNA polymerase
RNA virus - RNA dependent RNA polymerase
Reverse transcribing viruses (Retroviridae and Hepadnaviruses)
RNA dependent DNA polymerase = reverse transcriptase RNA is copied into DNA - 19Viral Replication - mutation an diversityDNA viruses
- stable genomes
- Homologous and non-homologous recombination
RNA viruses
- variable genomes
- error prone replication
- homologous and non-homolgous recombination
- quasispecies - 20Viral replication - transcription and translationProduction of mRNA using host cell enzymes, DNA dependent RNA polymerase (DNA viruses) or viral RdRPol (RNA viruses)
- processing, splicing
- transcriptional control via viral promoters (untranslated regions of genome)
- Co-ordinated gene expression
- important point of control - 21Viral growth characteristicsActive infection: one virus in = many viruses out
Acute = infection quickly resolved
Latent = virus lies dormant with very little replication and can be reactivated
HIV and retroviruses = permanent integratation of viral genome
Chronic = persistent long-term infection - 22Viral growth characteristicsUsing host cellular pathways
- Golgi secretion pathways (e.g. flaviviruses)
Cytolytic and destroy the cell (e.g. Rotavirus)
Budding and release
- From outer membrane, from internal vesicles (e.g. Herpes virus, Rotavirus, Vaccina virus)
- Assisted release (e.g. influenza) - 23Virus replication: Assembly and release- Using Host cellular pathways
- Golgi secretion pathways (e.g. flaviviruses)
- Cytolytic and destroy the cells (e.g. Rota virus)
Budding and release
- from outer membrane, from internal vesicles
- creation of double membrane vesicles (e.g. Herpes virus, Rotavirus, Vaccina virus) - 24Viral diversityOne virus does not equal one genetic sequence
In the population = different serotypes and genotypes
Individual person = quasispecies
Different subtypes within the population e.g. 6 different HCV genotypes
Quasispecies within the one patient: a swarm of viruses sequence variations - 25Viral QuasispeciesDiverse population, unselected, many variants
Most fit = major consensus
Selection pressure (drug, immune)
Most fit = major consensus - 26Viral quasispecies and drug resistanceQuasispecies allows genetic diversity
Random mutation generates drug resistant variants
Drug resistant variants are selected by drug pressure = treatment failure within patient
Transmission of drug resistance = treatment failure within the population - 27Viral epidemoiology and surveillanceSerology and virus detection by PCR
- in human population
- in animal reservoir - 28Respiratory virus - influenzaClinical Disease: upper respiratory tract illness
- infects respiratory epithelium
- fever, sore throat, malaise
Influenza B and C = human
Influenza A = zoonoses from water birds - 29Influenza A virus (IAV)Orthomyxoviridae
Negative sense single stranded RNA (-ssRNA)
Segmented genome
Subtypes - based on different haemaglutanin and neuramiidase proteins (e..g H1N1)
- vaccine preventable, antiviral treatments - 30Influenza A virus structure- Enveloped virus
- 80-120 nm virion
HA spikes - 31Influenza A virus GenomeSegmented genome
- 8 segments, 11 proteins, 0.9 - 3 kB
Spliced transcripts, different reading frames, overlapping reading frames - 32Influenza A virus - functions of protiensHA = haemagglutin, cell binding
NA = neuraminidase, cleavage and release from cell
NP = nucleoprotein, protection of RNA
M1 and M2 = matrix protiens
Non structural
NS1, NEP, NA = non structural proteins
PA, PB1, PB1-F2, PB2 = RNa polymerase, replication - 33Diversity of Influenza A virusNew strains by genome re-assortments = antigenic shift
Strain variation by genome mutation = antigenic drift - 34Antigenic shiftMajor change in virus, epidemic and pandemic outbreaks due to completely 'new' virus seen by immune system
- 35Antigenic driftMinor gradual change in virus, some new infections but not general evasion of herd immunity
- 36Other respiratory pathogensRespiratory syncytial virus (RSV)
Metapneumovirus
Parainfluenzavirus
Adenovirus
SARS coronavirus
Rhinovirus (common cold) - 37Arbovirus: West Nile virusArbovirus = athropod borne virus
Febrile illness and encephalitis as severe outcome
No vaccine
No anti-viral therapy
Flavivirus, positive ssRNA - 38West Nile virus: Life cycleMosquito Vector
Secondary bird reservoir
Maintenance vector, bridge vectors - 39West Nile virus: replication cycleBinding entry: receptor mediated endocytosis
Transcription and translation: involvement of ER for virus production
Genome replication: Involvement of the Golgi for virus release
Assembly and release - 40Important viruses that are related to West Nile VirusFlavivirus of Flaviviridae family
Hepatitis C virus = Hepacivirus of Flaviridae family - 41Other important arbovirusesAlpha Viruses: positive sense RNA viruses
Barmah Forest virus (BFV) - Australian
Ross Rover Virus (RRV) - Australian, arthritic virus
Chikungunya virus (CHKV) - emerging disease, arthritic virus - 42Hepatitis C VirusSingle Stranded RNA virus
Family Flaviviridae
Consists of a core genetic material (RNA) surrounded by icosahedral protective shell of protein
Further encased in lipid (fatty) envelope of cellular origin
Replication of HCV. Hepatocytes of the liver
Replicate in peripheral blood mononuclear cells
High error rate on virus' RNA dependent RNA polymerase
Mutation rate produces so many variants of virus is considered a quasispecies - 43HCV replicaiton cycleEntry: Receptor mediated endocytosis - multiple receptors
Involvement of Golgi for virus release
Involvement of ER for virus production - 44Hepatitis C virus: Diversity6 Different HCV genotypes (1-6)
Heterogeneity within genotypes
Quasispecies within patients
Signficance: Estimated that in most infections there already exists variants that can yield drug resistance - 45HCV and other hepatitis virusesAcute liver disease, 20% of people will clear the infection
Chronic disease
Long term persistence of virus, liver failure, can progress to hepatocellular carcinoma - 46Gastroenteritis: RotavirusGlobally most significant cause of gastroenteritis in children
Treatment = supportive
Vaccine available
Reoviridae (dsRNA)
Rotavirus A-E = mostly A in humans - 47Rotavirus: genomeNon-enveloped virus
Detectable in fecal samples in EM
Segmented genome
Post-translational cleavage of polyprotein
Alternative initiation sites
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- Immunology Karteikarten am Week 8 Viruses, erstellt von Paras Chrysostomou am 01/11/2016.
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