Lecture 21. Consequences of Viral Infection Flashcards
What is pathogenesis?
The ability/capability of the virus to cause disease
What is virulence?
Quantitive or relative measure of the pathogenesis of the infecting virus
What does avirulent mean?
Attenuated virus
How can virulence be quantitated?
Virus titre
Mean time to death
Mean time to appearance of disease
Measurement of fever, weight loss
Measurement of pathological lesions (poliovirus)
Reduction in CD4 T cell (HIV)
Case fatality ratio/hospitalisation rate
What is the mechanism of viral injury and disease?
Direct cytotoxicity of the virus
Virus-induced immunopathogenesis
Virus-induced immune suppression
Virus-induced transformation
What does poliovirus kill?
Neurons: paralysis of muscles innervated by those neurons
What does ebola virus damage?
Vascular endothelial cells cause haemorrhage
What is direct virus killing (cytotoxic diseases)?
Damage to the host may be a consequence of viral replication
What is virus-induced immunopathogenesis?
Tissue injury may reflect host defence mechanisms that include apoptosis or immune responses that target virus-infected cells
What is virus-induced immune suppression?
Some viruses can specifically target and infect cells of the immune system causing immunodeficiency.
The most prominent of these is HIV infection, which is known to cause AIDS
What causes cancers associated with some viral infections?
Indirect effects of immunosuppresion associated with HIV infection
What is associated with HBV or HPC infection?
Chronic inflammation
What family of viruses does HIV belong to?
Retroviruses
What are the two human pathogens that cause HIV?
HumanImmunodeficiencyVirus(HIV)
HumanT‐LymphotropicVirus(HTLV)
What is HIV enveloped by?
Two surface glycoproteins
How does HIV replicate?
Interaction between the viral attachment proteins which is known as gp120 and the cellular receptor CD4
Entry of the virus into the host cells
The viral nucleic acid is released from the capsid
Synthesis of viral proteins
Replication of nucleic acid
Assembly
What is the acute phase of HIV infection?
IscharacterisedbyinfectionofactivatedCD4+Tcellsin mucosallymphoidtissuesandthedeathofmanyinfected cells.
AtthisstageamodestreductioninCD4+Tcellcounts,butthenumberofbloodCD4+TcellsoftenreturnstonormalastheindividualmaycontinuetomakenewCD4+Tcells,andthereforethesecellscanbereplacedalmostasquicklyastheyaredestroyed.
What is the chronic phase of HIV infection?
VirusspreadsthroughoutthebodytoinfecthelperTcells,macrophages,anddendriticcellsinperipherallymphoidtissues.
Thischronicphasemaylastformanyyears.
Duringthistime,thevirusiscontainedwithinlymphoidtissues,andthelossofCD4+Tcellsisreplenishedfromprogenitors
Patientsareasymptomaticorsuffer fromminorinfections.
What is the AIDS phase of HIV infection?
Lymphnodesandthespleenaresitesof continuousHIVreplication
CelldestructionandthenumberofcirculatingbloodCD4+Tcellssteadily declines
NumberofcirculatingCD4+Tcellsthatare infectedatanyonetimemaybelessthan0.1%ofthetotalCD4+Tcellsinanindividual.
Eventually,thecontinuouscycleofvirusinfection,Tcelldeath,andnewinfectionleadstolossofCD4+Tcells: AIDSstage=CD4+Tcell<200cells/mm3
What are the clinical features of Acute HIV disease?
Fever, headaches, sore throat with pharyngitis, generalised lymphadenopathy, rashes
What are the clinical features during the clinical latency period of HIV?
Declining blood CD4+T cell count
What increases the membrane permeability?
Theproductionofviralproteinsincludinggb41,andgp120intheplasmamembraneandbuddingofviralparticles
What does a lethal influx of calcium cause?
Apoptosis
What causes osmotic lysis of the cell?
Influx of water
What targets infected CD4 cells?
Specific cytotoxic T cells
What are viral virulence genes?
Gene/genesproductsthataffectviralreplication
Geneencodingtoxins
Genesencodingmodulatorsoftheimmuneresponse
Gene/gensproductsthatenablethevirustospreadin thehost
What host gene protects against HIV infection?
CCR5:delta32mutation
How does being very young influence virulence?
Immatureimmuneresponses
How does being old influence virulence?
Lesselasticalveoli
Weakerrespiratorymuscles
Diminishedcoughreflex
Reducedrateofproductionofnewimmunecells
