Viral Infection And Pathogenesis 2 Flashcards
What influences disease severity
Virus virulence and host susceptibility
Myxomatosis host res eg
Myxoma virus fatal in eu rabbit but not in natural hist rabbit
Used by aussies to control rabbit pop in ’50s had a 90% kill rate but selection against virulent strain and for a more attenuated strain occured over time along with selection for incr res rabbits
Viral genes affecting virulence
Affecting repl ability
Affecting subversion of host mech
Affectiong inter and intra host spread
Vaccinia and pox virus eg of genetic virulence determinants
Several genes IDed that affect virulence some fx by interfering with host D eg disrupt IFN, deact complem, disrupt Antig pres and T cell recog, inhib inflam resp
Vaccinia encode epidermal GF causing hyperplastic cell growth at infection site favouring viral growth
Mousepox res/susceptibility genetic determinants
3 distinct gene loci involved that map to chromosomal regions involving MHC complex, complement and NK cells
Flu virulence genetic determinants
Dep on ability for HA cleavage into 2 chains by proteases in as many different cells as poss
The linker region between the 2 chains is key responsible for virulence
Eg in avian flu these viruses become rapidly dissem causing widespread infection incl in CNS. 83 outbreak caused by single aa change in H5 cleavage region
Other factors incl NS pro that interferes with IFN alpha and beta and TNF alpha fx
Flue host suscept genetic determinants
Mx gene, induced by type 1 IFN and fx by blocking virus transcription eg of single host gene giving res
Imm med viral dis
Imm syst expression involves some inflam, cell infiltration and tissue dam aka immunopathological
In normal cond these changes are ltd but with some viral infection they are a key cause of viral induced dis
Imm complex dis
If excess Ab then Ab bind to and completely coats antigen, if in equal amount the AbAg lattices formed, if Ag in excess then smaller complexes formed
Normally AbAg complex recog and cleared by RE cells but when Ag circulates for prolonged time (persistent Antigenemia) complexes prod more quickly than theyre cleared so cont to circ and can localise in small blood vessels and organs with fenestrated epi eg glomeruli of kidney, choroid plexus of brain, spleen, l nodes
Possibly bia Fc or comp rec interaction
Chronic glomerulonephritis
Imm complexes in kidney filtered by glomerular capillaries and some reenter blood and others retained by local phagocytic cells(mesangial cells)
When imm cimplex form over long tine period, normal remival mech swamped and deposits accum with comp components just outside blood vessels
Mesangial cells enlarge and multiply, BM struct alters between glom cap and urinary compartmet causing filtration fx of glom to be impaired eventually can cease to fx - chronic glomerulonephritis
Other depostion disease and places of imm complexes
In walls of small blood vessels in skin and joints where they can induce type 3 hypersens and also in choroid plexus
Severe cases can for small red nodules in skin or blood vessels
Im complex dis aleutian dis virus of mink eg
Infection cause high Ab level with weakening neut ability
Get imm complex deposition in glom and blood vessels cause nephritis and haemorrhage
Im complex FeLV eg
35% of persist infected cats died of glomneph
25% of cats with lymphosarcoma had AbAgcomp complsxes in kidneys
Im complex EIAV eg
High levels of circ imm complex and corresponding kidney deposition causin glomneph
RBCs become coated in Ab/complem causing active haemolysis, incr osmotic fragility and erythrophagocytosis causing anaemia
Ab dep enhancement of virus infect eg EIAV
Bind of Ab to virus and subseq recog by Fc rec on macro causes phagocyt and infection of cell
So gives a means of more efficient infection than via normal viral rec
