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lördag 17 augusti 2013

Kertausta HIV genomista

http://www.mcld.co.uk/hiv/?q=HIV%20genome

HIV genomi

Kokopitkää HIV genomia koodaa yksi pitkä RNA säie. Vapaassa viruspartikkelissa on  varsinaisesti kaksi tällaista   erillistä, täysin samnlaista RNA säiettä. Tämä on se (tiivein)  muoto, mikä tällä viruksella on, kun se on vapaana viruspartikkelina. Mutta kun virus integroituu isännän omistamaan DNA- genomiin ( proviruksena),  viruksen genominen sisältö on koodautuneena myös DNA- muotoisena.

This is the form it has when it is a free virus particle. When the virus is integrated into the host's DNA genome (as a provirus) then its information too is encoded in DNA.

Alla on  yksinkertaisen kaavamaisesti kuvattuna, miten geenit ovat asettautuneena HIV virukseen. On muistettava, että HIV- 1 ja HIV-2 virukset ovat aika erilaisia. Alla on geenien nimet luettelona ja niistä saa lisätietoa klikkaamalla.

The following image shows roughly how the genes are laid out in HIV (remember that HIV-1 and HIV-2 are quite different). Click on a gene's name for more information.
A rough map of the genomic layout of HIV
This diagram is based on a fantastic map of the HIV-1, HIV-2, and SIV genomes, available at
hiv-web.lanl.gov/content/immunology/pdf/2000/intro/GenomeMaps.pdf

HIV genomin geenit ovat seuraavat:
The genes in HIV's genome are as follows:
  • gag (coding for the viral capsid proteins)
  • pol (notably, coding for reverse transcriptase)
  • (NB. gag and pol together can be expressed in one long strand called "gag-pol")
  • env (coding for HIV's envelope-associated proteins)
  • And the regulatory genes ( Säätelevät geenit ovat seuraavat) 
  • tat
  • rev
  • nef
  • vif
  • vpr
  • vpu (N.B. not present in HIV-2)
  • vpx (N.B. not present in HIV-1)
 HIV genomissa on myös  genomin molemman päädyn pitkä toistojakso  (LTR), mikä ei ole varsinainen geeni vaan RNA/DNA sekvenssi, mikä on samanlainen molemmissa päädyissä  ja sillä on joitain rakenteellisia ja säätelyllisiä tarkoituksia. 

The HIV genome also has a "Long Terminal Repeat" (LTR) at each end of its genome - not quite a gene, but a sequence of RNA/DNA which is the same at either end and which serves some structural and regulatory purposes.

tisdag 6 augusti 2013

HIV rokotteesta: Nef/Tat antigeenit huomioitu

http://www.ncbi.nlm.nih.gov/pubmed/21963936

måndag 5 augusti 2013

HIV 1 Nef kaappaa T-imusolun immunologisen vasteen päävaihteen. säätelyn.

HIV 1 Nef indusoi trans-Golgi-verkostoon liittyneen Lck signaloinnin, mikä vaikuttaa immunologisen synapsin modulatiota firuksen replikaation eduksi. Samalla ihmisessä tauti pahenee. Viruksen Nef- tekijä saattaa epäkuntoon immunologisten synapsien järjestyneisyyden, mikä vallitsee T-imusolujen CD4+ ja antigeeniä esittävän(APC) B- lymfosyytin kesken, mikä koskeen TCR t-soluresetroin proksimaalista signalointia. Paradoksaalisesti Nef samlla lisää distaalista TCR- signalointia infektoituneissa T- CD4 + soluissa, minkä vaikutuksen katsotaan edistävän AIDS taudin patogeneesiä. ....... Blood. 2012 Jan 19;119(3):786-97. doi: 10.1182/blood-2011-08-373209. Epub 2011 Nov 28. HIV-1 Nef compensates for disorganization of the immunological synapse by inducing trans-Golgi network-associated Lck signaling. Pan X, Rudolph JM, Abraham L, Habermann A, Haller C, Krijnse-Locker J, Fackler OT. SourceDepartment of Infectious Diseases, Virology, University Hospital Heidelberg, Germany Abstract The Nef protein of HIV-1 facilitates viral replication and disease progression in vivo. Nef disturbs the organization of immunological synapses between infected CD4(+) T lymphocytes and antigen-presenting B-lymphocytes to interfere with TCR proximal signaling. Paradoxically, Nef enhances distal TCR signaling in infected CD4(+) T lymphocytes, an effect thought to be involved in its role in AIDS pathogenesis. ......´ Nef aiheuttaa -solurespetorin solunsisäistä aitioitumista ja täten muuntaa tämän TCR reseptorin vastetta antigeenistimulaatioon. ..... Using quantitative confocal microscopy and cell fractionation of Nef-expressing cells and HIV-1-infected primary human T lymphocytes, we found that Nef induces intracellular compartmentalization of TCR signaling to adjust TCR responses to antigenic stimulation...... Nef suuntaa poispäin plasmakalvosta toiselle reitille T-soluresptorin (TCR) signaloivan päävaihteen Lck kinaasiaktiivit altaat ja johtaa ne trans-Golgiverkostoon (TGN) . Täten estyy aktiivien Lck -tekijöiden rekrytointi immunologisiin synapseihin TCR:n jo puututtua asiaan ja niin signaalin alkuunpano plasmakalvossa rajoittuu. Nef reroutes kinase-active pools of the TCR signaling master switch Lck away from the plasma membrane (PM) to the trans-Golgi network (TGN), thereby preventing the recruitment of active Lck to the immunological synapse after TCR engagement and limiting signal initiation at the PM. ..... Mutta sensijaan Nef triggeröi trans-golgin verkostoon (TGN) liittyvän Ras- Erk- signaloinnin Lck:sta riippuvan aktivaation , mikä jää nyt edistämään T-imusolujen elossapysymistekijää IL- 2 ja näin lisäämään viruksen leviämistä ( immunologisesti epätarkoiksi tehdyissä) T- imusoluissa. ..... Instead, Nef triggers Lck-dependent activation of TGN-associated Ras-Erk signaling to promote the production of the T lymphocyte survival factor IL-2 and to enhance virus spread. ..... Jos saadaan aikaan Lck plasmamembraanikuljettajan Unc119 yliexpressio, palautuu Nef tekijän aiheuttamat väärentymät Lck- kulkeutumisissa ja T-solureseptorin signaloinnissa. Overexpression of the Lck PM transporter Unc119 restores Nef-induced subversions of Lck trafficking and TCR signaling...... Siis: HIV 1- viruksen N ef- tekijä kaappaa Lck-tekijän ( päävaihteen) sorteerauksen aktivoimalla selektiivisesti trans-golgin verkostoon(TGN) liittyvät puolet aitioituneen T- imusolureseptorin (TCR) signalointifunktiosta.Räätälöimällä kokoon T-imusolun antigeenistimulaatiolle antamia vasteita Nef optimoi miljöön HIV- 1 virukwsen replikoitumisen eduksi. .....Nef therefore hijacks Lck sorting to selectively activate TGN-associated arms of compartmentalized TCR signaling. By tailoring T-lymphocyte responses to antigenic stimulation, Nef optimizes the environment for HIV-1 replication.

Miten HIV muuntaa endoplasmisen verkoston ja Golgin laitteen funktion?

Showing results for golgi apparatus in hiv infection. Your search for Golgi apparate in HIV infection retrieved no results. Results: 1 to 20 of 34 Select item 22711344 1.-----In vitro replication phenotype of a novel (-1G) hepatitis B virus variant associated with HIV co-infection. Cabuang LM, Shaw T, Littlejohn M, Colledge D, Sozzi V, Soppe S, Warner N, Thompson A, Preiss S, Lam N, Walsh R, Lewin SR, Thio CL, Matthews G, Locarnini SA, Revill PA. J Med Virol. 2012 Aug;84(8):1166-76. doi: 10.1002/jmv.23328. PMID:22711344[PubMed - indexed for MEDLINE] Free PMC Article Related citations Select item 22537596 -----2.Identification of a highly conserved valine-glycine-phenylalanine amino acid triplet required for HIV-1 Nef function. Meuwissen PJ, Stolp B, Iannucci V, Vermeire J, Naessens E, Saksela K, Geyer M, Vanham G, Arien KK, Fackler OT, Verhasselt B. Retrovirology. 2012 Apr 27;9:34. doi: 10.1186/1742-4690-9-34. PMID:22537596[PubMed - indexed for MEDLINE] Free PMC Article Related citations Select item 22123847 -----3.HIV-1 Nef compensates for disorganization of the immunological synapse by inducing trans-Golgi network-associated Lck signaling. Pan X, Rudolph JM, Abraham L, Habermann A, Haller C, Krijnse-Locker J, Fackler OT. Blood. 2012 Jan 19;119(3):786-97. doi: 10.1182/blood-2011-08-373209. Epub 2011 Nov 28. PMID:22123847[PubMed - indexed for MEDLINE] Free Article Related citations Select item 21567396 -----4.HIV-1 Nef perturbs the function, structure, and signaling of the Golgi through the Src kinase Hck. Hiyoshi M, Takahashi-Makise N, Yoshidomi Y, Chutiwitoonchai N, Chihara T, Okada M, Nakamura N, Okada S, Suzu S. J Cell Physiol. 2012 Mar;227(3):1090-7. doi: 10.1002/jcp.22825. PMID:21567396[PubMed - indexed for MEDLINE] Related citations Select item 21563830 -----5.Macrophage bridging conduit trafficking of HIV-1 through the endoplasmic reticulum and Golgi network. Kadiu I, Gendelman HE. J Proteome Res. 2011 Jul 1;10(7):3225-38. doi: 10.1021/pr200262q. Epub 2011 Jun 6. PMID:21563830[PubMed - indexed for MEDLINE] Free PMC Article Related citations Select item 20643940 -----6.Envelope glycans of immunodeficiency virions are almost entirely oligomannose antigens. Doores KJ, Bonomelli C, Harvey DJ, Vasiljevic S, Dwek RA, Burton DR, Crispin M, Scanlan CN. Proc Natl Acad Sci U S A. 2010 Aug 3;107(31):13800-5. doi: 10.1073/pnas.1006498107. Epub 2010 Jul 19. PMID:20643940[PubMed - indexed for MEDLINE] Free PMC Article Related citations Select item 20147389 -----7.CD317/tetherin is enriched in the HIV-1 envelope and downregulated from the plasma membrane upon virus infection. Habermann A, Krijnse-Locker J, Oberwinkler H, Eckhardt M, Homann S, Andrew A, Strebel K, Kräusslich HG. J Virol. 2010 May;84(9):4646-58. doi: 10.1128/JVI.02421-09. Epub 2010 Feb 10. PMID:20147389[PubMed - indexed for MEDLINE] Free PMC Article Related citations Select item 19838694 -----8.Assembly and intracellular trafficking of HLA-B*3501 and HLA-B*3503. Thammavongsa V, Schaefer M, Filzen T, Collins KL, Carrington M, Bangia N, Raghavan M. Immunogenetics. 2009 Dec;61(11-12):703-16. doi: 10.1007/s00251-009-0399-2. PMID:19838694[PubMed - indexed for MEDLINE] Free PMC Article Related citations Select item 19740980 -----9.Antagonism to and intracellular sequestration of human tetherin by the human immunodeficiency virus type 2 envelope glycoprotein. Le Tortorec A, Neil SJ. J Virol. 2009 Nov;83(22):11966-78. doi: 10.1128/JVI.01515-09. Epub 2009 Sep 9. PMID:19740980[PubMed - indexed for MEDLINE] Free PMC Article Related citations Select item 19648286 -----10.Golgi dysfunction is a common feature in idiopathic human pulmonary hypertension and vascular lesions in SHIV-nef-infected macaques. Sehgal PB, Mukhopadhyay S, Patel K, Xu F, Almodóvar S, Tuder RM, Flores SC. Am J Physiol Lung Cell Mol Physiol. 2009 Oct;297(4):L729-37. doi: 10.1152/ajplung.00087.2009. Epub 2009 Jul 31. PMID:19648286[PubMed - indexed for MEDLINE] Free PMC Article Related citations Select item 19448977 -----11.The functional antagonist Met-RANTES: a modified agonist that induces differential CCR5 trafficking. Kiss DL, Longden J, Fechner GA, Avery VM. Cell Mol Biol Lett. 2009;14(4):537-47. doi: 10.2478/s11658-009-0017-1. Epub 2009 May 14. PMID:19448977[PubMed - indexed for MEDLINE] Related citations Select item 17893228 -----12.Interaction between Hck and HIV-1 Nef negatively regulates cell surface expression of M-CSF receptor. Hiyoshi M, Suzu S, Yoshidomi Y, Hassan R, Harada H, Sakashita N, Akari H, Motoyoshi K, Okada S. Blood. 2008 Jan 1;111(1):243-50. Epub 2007 Sep 24. PMID:17893228[PubMed - indexed for MEDLINE] Free Article Related citations Select item 17331040 -----13.Molecular characterization of the HIV type 1 subtype C accessory genes vif, vpr, and vpu. Bell CM, Connell BJ, Capovilla A, Venter WD, Stevens WS, Papathanasopoulos MA. AIDS Res Hum Retroviruses. 2007 Feb;23(2):322-30. PMID:17331040[PubMed - indexed for MEDLINE] Related citations Select item 17034868 -----14.Binding kinetics, uptake and intracellular accumulation of F105, an anti-gp120 human IgG1kappa monoclonal antibody, in HIV-1 infected cells. Clayton R, Ohagen A, Goethals O, Smets A, Van Loock M, Michiels L, Kennedy-Johnston E, Cunningham M, Jiang H, Bola S, Gutshall L, Gunn G, Del Vecchio A, Sarisky R, Hallenberger S, Hertogs K. J Virol Methods. 2007 Jan;139(1):17-23. Epub 2006 Oct 10. PMID:17034868[PubMed - indexed for MEDLINE] Related citations Select item 16385629 -----15.HIV-1 down-regulates the expression of CD1d via Nef. Chen N, McCarthy C, Drakesmith H, Li D, Cerundolo V, McMichael AJ, Screaton GR, Xu XN. Eur J Immunol. 2006 Feb;36(2):278-86. PMID:16385629[PubMed - indexed for MEDLINE] Related citations Select item 15569716 -----16.HIV-1 Nef disrupts MHC-I trafficking by recruiting AP-1 to the MHC-I cytoplasmic tail. Roeth JF, Williams M, Kasper MR, Filzen TM, Collins KL. J Cell Biol. 2004 Dec 6;167(5):903-13. Epub 2004 Nov 29. PMID:15569716[PubMed - indexed for MEDLINE] Free PMC Article Related citations Select item 12747276 -----17.Autoantibodies and human immunodeficiency viruses infection: a case-control study. Chretien P, Monier JC, Oksman F, San Marco M, Escande A, Goetz J, Cohen J, Baquey A, Humbel RL, Sibilia J. Clin Exp Rheumatol. 2003 Mar-Apr;21(2):210-2. PMID:12747276[PubMed - indexed for MEDLINE] Related citations Select item 11983247 -----18.Analysis of the immune response and viral evolution during the acute phase of SIV infection. Horton H, Vogel T, O'Connor D, Picker L, Watkins DI. Vaccine. 2002 May 6;20(15):1927-32. PMID:11983247[PubMed - indexed for MEDLINE] Related citations Select item 11806977 -----19.Pathways for internalization and recycling of the chemokine receptor CCR5. Mueller A, Kelly E, Strange PG. Blood. 2002 Feb 1;99(3):785-91. PMID:11806977[PubMed - indexed for MEDLINE] Free Article Related citations Select item 11289809 -----20.HIV-1 Nef blocks transport of MHC class I molecules to the cell surface via a PI 3-kinase-dependent pathway. Swann SA, Williams M, Story CM, Bobbitt KR, Fleis R, Collins KL. Virology. 2001 Apr 10;282(2):267-77. PMID:11289809[PubMed - indexed for MEDLINE] Related citations