VIRUSOLOGIJA

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VIRUSOLOGIJA (VIRUSI UN ARPUSHROMOSOMU GENETISKIE
ELEMENTI)
VIRUSU UN ARPUSHROMOSOMU ELEMENTU GRUPAS Virusi
un laundabigie audzeji
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• Laundabigie audzeji
• šunas cikls
• audzeju attistiba
• onkogeni
• tumoru supresori
• virusu onkogeneze
• virusi genu terapija

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Šunas cikla regulacija
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Normala šuna kultura (primara šunu
kultura) Morfologiskas un molekularas
diferenciacijas pazimes Atkariba no audu tipa
specifiskiem augšanas faktoriem Piesaistišanas
atkariga (adheranta) augšana Augšanas
kontaktinhibicija (monoslanis) Neliels
metabolisma atrums Diploids hromosomu
skaits Ierobežots dališanas ciklu skaits
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Audzeja attistibas etapi
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Audzeja indukcija Hromosomu aberacijas
(Filadelfijas hromosoma 9 - 22 translokacija)
Audzeja indukcija 8 Oksoguanozins /
oksoguanozina glikozilaze
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Virusu ierosinata onkogeneze
RNS virusi Permisivas, dalošas un virusu
producejošas šunas Akuti transformejoši
retrovirusi (onkogenu transdukcija) Protoonkogeni
- virusu onkogeni (c-myc / v-myc) Defektivi,
repliceties nespejigi virusi Atškiribas nav
intronu var but saisinati (v-src) nest
mutacijas (v-ras) veidot vienotu proteinu ar
virusa gag vai env genu produktiem, tiek aktivi
ekspreseti LTR kontrole.
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Michael Bishop, Harold Varmus Nobela premija
medicina un fiziologija, 1989 Par virusu onkogenu
šunas izcelsmes atklašanu
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Virusu ierosinata onkogeneze
Leni transformejoši virusi (inserciju
mutageneze) Repliceties spejigi virusi. ALV,
MMTV Leni transformejoši virusi
(transaktivacija) Repliceties spejigi virusi.
HTLV, BLV (tax) Transformacijas testi RSV, NIH
3T3
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Transformacija un morfologija
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Virusu onkogenu izcelsme
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Virusu onkogenu šunu analogu funkcijas
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Virusu onkogenu šunu analogu funkcijas
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DNS virusu onkogenais potencials
HPV HBV EBV HHV-8 SV-40 JK BK
TRAFs - TNF receptor associated factors, family
of proteins primarily involved in the regulation
of inflammation, antiviral responses and
apoptosis. PP2A - Protein phosphatase 2.
Bergonzini et al. Infectious Agents and Cancer
2010, 511 http//www.infectagentscancer.com/conte
nt/5/1/11
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Antionkogeni (tumoru supresori, piemers RB
proteins)
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Šunas cikla regulatori antionkogeni
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Ar cilveka audzejiem saistitie virusi
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RNS virusu regulatoro proteinu onkogenais
potencials
PKB. Akt - a serine/threonine-specific protein
kinase that plays a key role in multiple cellular
processes p300 - E1A binding protein p300 CBP,
CREB-2 - CREB binding protein STAT5 - proteins
involved in cytosolic signalling and in mediating
the expression of specific genes Telomerase
reverse transcriptase - hTERT in humans
Bergonzini et al. Infectious Agents and Cancer
2010, 511 http//www.infectagentscancer.com/conte
nt/5/1/11
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Dzivnieku dsDNS virusi
Adenovirusu onkogeneze
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Pieradita loma cilveka onkogeneze klinika
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HPV un cilveka laundabigie audzeji
mucosal cutaneous (glotadu un adas) HPV long
control region (LCR) HPV traskribe tikai vienu
DNS kedi
JOURNAL OF VIROLOGY, Nov. 2004, p. 1145111460
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HPV un cilveka laundabigie audzeji
Minimalais HPV 16 genoms pec integracijas
saimniekšunas hromosoma
JOURNAL OF VIROLOGY, Nov. 2004, p. 1145111460
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HPV un cilveka laundabigie audzeji
JOURNAL OF VIROLOGY, Nov. 2004, p. 1145111460
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Poliomas viruss JK un cilveka laundabigie audzeji
Oncogene (2006) 25, 52945301
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D.J. Kenan et al. The oncogenic potential of BK-
polyomavirus is linked to viral integration into
the human genome J Pathol 2015 237 379389
The insertion resulted in fusion of the VP1
coding sequences with MYBPC1 exonic sequences,
redicting a fusion protein consisting of the
first 309 codons of VP1, followed by six
out-of-frame codons in MYBPC1 exon 26, followed
by a stop codon.
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Poliomas virusi un cilveka laundabigie audzeji
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Poliomas virusi un cilveka laundabigie audzeji
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Poliomas virusi un cilveka laundabigie audzeji
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Poliomas viruss SV40 un cilveka laundabigie
audzeji
Expert Rev Respir Med. 2011 October 5(5)
683697.
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HBV HCV virusi un cilveka laundabigie audzeji
Adrian M. Di Bisceglie, M.D. Hepatitis B And
Hepatocellular Carcinoma Hepatology. 2009 May
49(5 Suppl) S56S60.
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HBV un HCV virusu genoma struktura
NATURE REVIEWS CANCER VOLUME 13 FEBRUARY 2013
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NATURE REVIEWS CANCER VOLUME 13 FEBRUARY 2013
123
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HBV viruss un hepatocelulara karcinoma (HCC)
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EBV HHV8 virusi un cilveka laundabigie audzeji
http//digitalunion.osu.edu/r2/summer06/pepple/res
earch/index.html
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EBV HHV8 virusi un cilveka laundabigie audzeji
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EBV HHV8 virusi un cilveka laundabigie audzeji
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HTLVI HTLVII virusi un cilveka laundabigie
audzeji
M Boxus and L Willems Mechanisms of HTLV-1
persistence and transformationBritish Journal of
Cancer (2009) 101(9), 1497 1501
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HTLVI HTLVII virusi un cilveka laundabigie
audzeji
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HTLVI HTLVII virusi un cilveka laundabigie
audzeji
www.intechopen.comHuman T-Cell Lymphotropic
Virus (HTLV-1) and Adult T-Cell Leukemia
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Genu terapijas principi
D. Ibraheem et al. / International Journal of
Pharmaceutics 459 (2014) 70 83
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Virusu genu terapijas vektori
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Adenovirusu genu terapijas vektori
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Adenovirusu genu terapijas vektori
http//www.tankonyvtar.hu/hu/tartalom/tamop425/001
1_1A_Molekularis_terapiak_en_book/images/image025.
png
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AAV genu terapijas vektori
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http//cmr.asm.org/content/21/4/583/F2.large.jpg
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Herpevsirusu genu terapijas vektori
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Herpesvirusu genu terapijas vektori
9-(4-18 F-Fluoro-3-hydroxymethylbutyl)guanine
(18 F-FHBG) is a sensitive and specific PET
reporter probe for imaging the PET reporter
genes, herpes himplex 1 thymidine kinase
(HSV1-tk)
http//jnm.snmjournals.org/content/45/9/1560/F1.la
rge.jpg
http//www.slideshare.net/Aparajitha_Anne/gene-del
ivery-system
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Cerepro 2004, Ark Therapeutics Group
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Lentivirusu genu terapijas vektori
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Lentivirusu genu terapijas vektori
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Rerovirusu genu terapijas vektori
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Nevirusu genu terapijas instrumenti
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Genu terapijas virusu vektori
T. Wirth et al. / Gene 525 (2013) 162169
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Genu terapijas izmeginajumu merki