SAMMANFATTNING PÅ SVENSKA

Endogena retrovirus - våra inneboende virus Är de till nytta och/eller skada för människan?

Människans arvsmassa består av så kallat DNA, som i sin tur bygger upp våra gener. Gener överför olika egenskaper från generation till generation. De “inneboende” virus jag har undersökt, så kallade endogena virus, finns precis som gener i vår arvsmassa och ärvs på samma sätt. Kännetecknet för ett endogent virus är en viss kombination av olika gener av samma sort som finns hos retrovirus. Det mest kända exemplet på retrovirus är HIV, som ger den dödliga sjukdomen AIDS. HIV-viruset kan ta sig in i en cell och sätta sig i arvsmassan. Däremot kommer inte HIV att ärvas till nästa generation utan istället smitta från person till person. För att ett retrovirus ska bli ett av de inneboende retrovirusen krävs att en spermie eller ett ägg infekteras. Då kommer retroviruset vidare till nästa generation och kommer att finnas i varje cell.

De virus som vi redan bär på verkar inte vara farliga för oss människor. Istället kan vi se dem som spår efter urgamla infektioner som våra förfäder fick för flera miljoner år sedan. Det som är intressant med dessa “fotspår” är att en del fortfarande kan tillverka ämnen (virusproteiner) som behövs för att ett virus ska kunna förflytta sig, och således infektera en ny individ. En del forskningsresultat tyder på att de endogena virusen skulle kunna vara till nytta för oss. Efter att ha levt i symbios med “våra” virus så länge som flera miljoner år, kan det vara så att vi människor till slut dragit nytta av en del av virusets egenskaper.

I ett försök att komma närmare en lösning på vad retrovirus gör i arvsmassan hos människan har jag försökt besvara följande frågor;

1. Var finns virus i arvsmassan och hur många är de?

2. I vilka organ och vävnader är de aktiva (när tillverkar de virusämnen)? Hur mycket virusproteiner tillverkas i jämförelse med andra kända proteiner?

3. Vid vilka hälsotillstånd är de aktiva?

4. Kan svaren från ovanstående frågor ge en vägledning om de inneboende virus kan spela någon viktig roll för oss? Är de sjukdomsalstrande eller behöver vi dem för överlevad?

För att ta reda på om virus kan starta sjukdomar måste det först finnas uppgifter om vad som är normalt. Resultat jag fått fram i avhandlingen visar bl. a. hur aktiva virus är i friska individer och i vilka kroppsorgan. Det ger en bakgrundskunskap som är viktig

t.ex. vid eventuella framtida transplantationer. Kunskapen behövs för att kunna bedöma risken för att grisens inneboende virus kan smitta människa.

ACKNOWLEDGEMENTS

This work was carried out at the department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University Hospital. Financial support was provided by the Swedish Cancer Society, Lions Uppsala, and Selanders Foundation.

I would like to express my sincere gratitude to:

Prof. Erik Larsson, my supervisor, for your genuine enthusiasm concerning science and particularly endogenous retroviruses, for encouragement, for contributing to the other 50% of our research group, and for the many times you trusted me to represent it;

Prof. Jonas Blomberg, my part-time mentor for the last two years, for sharing your wide knowledge about retroviruses and bioinformatics; having time for discussions and for providing excellent virology seminars;

Associate Prof. Göran Andersson, my molecular biology-mentor, who, luckily, returned to Sweden, for co-authorship and good “HERV”-collaboration;

my collaborators and co-authors in alphabetical order;

Johan Botling, Anna Dimberg, Lars Eriksson, Graham Forrest, Jan Grawé, Simon Gronowitz, Fredrik Hedborg, Angela Horsfall, Patric Jern, Claes Källander, Per-Uno Malmström, Malik Merza, Ove Nilsson, Fredrik Pontén, Petter Ranefall, Shirley Rigby, Charlotte Rolny, Niclas Setterblad, Jürgen Scherer, Johan Sundström, Ann-Cathrin Svensson, Ralf Tönjes, Zhihong Yun and Fredrik Öberg;

Dr. Maurice Cohen, for the opportunity to visit you and your research group at Abbott Laboratories, Chicago; many thanks to you and your family;

Prof. Patrick Venables and PhD. Tracey Mitchell, for inviting me to the Kennedy Institute of Rheumatology, London, and for their hospitality, welcoming me in their home during my visits; Prof. Dixie Mager and PhD. Patrik Medstrand for their kind permission to use the HERV-tree in this thesis (Figure 3);

all people, from the Clinic and the University, who I had the pleasure to meet during my years at the unit of Pathology, Uppsala, among others; Görel, Ulrika L, Erik B., Pernilla E Ulf T. and Micke K;

William and Viktor for a variety of computer assistance, whenever needed, William also for have being a nice room mate;

Rehné E, Gunilla T, Gunilla Å, and especially Eva B, for all sorts of help concerning administration;

Frank Bittkowski for teaching micro photographing;

Annika Hermansson and Marianne Kastemar for your expertise in cell culture, among other things;

Sten-Sture lab; Anna D, Anna H, Lina, Inger, Karolina, Pernilla M, Fredrik, Thomas, Helena JW, Helen, Karin and Simon; for Friday gatherings and good company; especially I would like to thank Prof. Kenneth Nilsson for inviting me to the haematology lab, and together with Anna Dimberg, Fredrik Öberg and Inger Karlberg, having fruitful collaborations;

the Virology seminar group at the department of Clinical Virology; Patric, Anna F, Zhihong, Göran, Amal, Nahla, Dimitrij, Widar and others for a friendly atmosphere;

former members of “hörnfamiljen” The Busch-Larsson-lab, Ingrid Backlund, Eva Wahlund, Kenneth Wester, Lila Shokohideh, Ann-Christin Melén Boudin, Katarina Engström and Levent Akyürek for immunohistochemical expertise, friendship and a lot of humour throughout the years;

Kenneth Wester, for fruitful collaborations and co-authorship, a lot of fun conversations and for becoming a dear friend during our (sometimes long) way becoming PhD students;

Ann-Christin Melén Boudin, my sectioning mentor and sincere friend, for good times in the lab, horseback riding, and great hospitality from you and your family;

the “chicks” Mia and Marie for your happy lab-mood, and Mia also for being my WW friend; Åsa, Anna D, Göran and Thomas S for pep talks and company during late nights in the lab; Åsa also for our superb habit of having “fruktstunder”;

my room mates from “Kardborren”; Göran, Åsa, Magnus, Jessica and Lina;

the poker(?) club; Monica, Lotta, Susanne and the NY exile-members Lene and Ulrica for sharing fun and unpredictable evenings;

Carolina Rydin, Lene Uhrbom and Ulrica Westermark, all of which I first met in the lab, for dear friendship and fabulous family-dinners with a lot of bumping around in the kitchen;

Anna-Carin, Lena, and Karin, for friendship, countless hospital-lunches; and together with Dan, Peter and Erik, for a lot of fun and memorable times;

Maria and Viktoria, for “togetherness” and for keeping my dialect;

my relatives Mimmi, Ginge, Ecke, Kajsa Torbjörn, Liselotte, Lina, Ylva and Therese for pleasant family events at Tallmas and elsewhere;

the Lorant family, Gizella, Stefan, Eva, Urban, and Margit for welcoming me in their family and for taking so good care of me;

my parents Boel and Rolf for your love and encouragement; my brother Niklas for being just the brother I want; Anna-Karin, my dear sister in law, for taking good care of Niklas and Lovisa; Tomas, with lots of love, for your support and for being the one you are.

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