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Hasslung, Frida, 2003. Interferon-α-modulatory sequences from the genome of porcine circovirus type 2. SLU, Dept. of Molecular Biosciences, Uppsala. Uppsala: SLU, Dept. of Molecular Biosciences

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Abstract

Porcine circovirus (PCV) type 2 is an emerging pathogen among pigs, which has been associated with several severe disease syndromes. To date little is known of the pathogenesis and epidemiology of PCV, and how the virus affects the immune system of the host. To evaluate one possible mechanism of pathogenesis, the genome of PCV-2 was examined for content of CpG-motifs. Five 20 nucleotide long sequences from the genome were tested for their ability to induce production of IFN-a by porcine peripheral blood mononuclear cells (PBMC). One of the oligodeoxynucleotides (ODNs) proved to inhibit the IFN-a production induced by the other ODNs that were stimulatory. The inhibitory ODN (PCV-2/1) was tested against other known inducers of IFN-a and showed a variable degree of inhibitory action depending on the construct of the inducer. ODNs containing phosphorothioate backbone and poly- G- sequences seemed more resistant to inhibition. Also, the inhibitory activity of ODN PCV-2/1 differed against the viral inducers Aujeszky´s disease virus (ADV) and Sendai virus (SV), and the plasmid pcDNA3. Inhibition was most effective against ADV, moderately effective against pcDNA3, but did not affect the IFN-a production induced by SV. The variation in sensitivity to inhibition among the agents could be due to differences in target cell populations. The presence of immune modulatory sequences in the genome of PCV-2 could possibly explain parts of the pathogenesis of the virus.

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Porcint circovirus (PCV) typ 2 har på senare tid uppmärksammats i växande
omfattning, och har associerats med flera allvarliga sjukdomssyndrom hos gris.
Man vet fortfarande mycket lite om virusets patogenes och epidemiologi, och hur
det påverkar immunsystemet i värddjuret. För att undersöka en möjlig mekanism i
patogenesen studerades genomet av PCV-2 med avseende på förekomst av CpGmotiv.
Fem sekvenser om 20 nukleotider vardera valdes ut från genomet och deras
förmåga att inducera IFN-a i perifera mononukleära blodceller (PBMC) testades.
En av oligonukleotiderna (oligos) visade sig kunna hämma IFN-a produktionen
som inducerats av de övriga fyra oligos. Den hämmande oligon (PCV-2/1) testades
mot andra typer av kända inducerare och visade en varierande förmåga att inhibera
IFN-a produktion beroende på konstruktionen av induceraren. Oligo vars kedja till
en del utgjordes av fosfotioater istället för fosfodiestrar, samt innehöll upprepade
G- sekvenser I 3´- änden verkade mer resistenta mot den inhibitoriska aktivitet hos
PCV-2/1. Dessutom var PCV-2/1 inhiberande i varierande grad mot olika typer av
virala och bakteriella inducerare. Aujeszky´s disease virus (ADV) hämmades
effektivt medan plasmiden pcDNA3 bara hämmades delvis. IFN-a produktionen
inducerad av Sendaivirus (SV) påverkades inte av PCV-2/1. Mekanismerna bakom
denna variation är inte känd, men kan bero på vilka cellpopulationer som aktiveras
av induceraren. Fyndet att PCV-2-genomet innehåller IFN-a-modulerande
sekvenser kan bidra till ökad förståelse av virusets patogenes.

Main title:Interferon-α-modulatory sequences from the genome of porcine circovirus type 2
Authors:Hasslung, Frida
Supervisor:Fossum, Caroline
Examiner:UNSPECIFIED
Series:Examensarbete / Sveriges lantbruksuniversitet, Fakulteten för veterinärmedicin och husdjursvetenskap, Veterinärprogrammet
Volume/Sequential designation:2003:19
Year of Publication:2003
Level and depth descriptor:Other
Student's programme affiliation:3050A Veterinary Medicine Programme (admitted before July 1, 2007) 330 HEC
Department:(VH) > Dept. of Molecular Biosciences
Keywords:interferon, porcine circovirus, PCV-2, CpG, inhibitory
URN:NBN:urn:nbn:se:slu:epsilon-s-7318
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-s-7318
Subjects:Veterinary science and hygiene - General aspects
Animal diseases
Language:English
Deposited On:02 Oct 2017 07:20
Metadata Last Modified:02 Oct 2017 07:20

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