Vandaag is rood… de kleur van een virus.
Het vergeten neefje van de herpesfamilie
Of we het nu leuk vinden of niet, bijna iedereen is wel bekend de herpesfamilie, de meesten wellicht door de beruchte koortslip. Er is echter een virus in deze familie dat nooit zo in de belangstelling heeft gestaan, ondanks dat zo’n 85% van de mensheid ermee besmet is: humaan herpesvirus type 7 (HHV-7). Dat betekent dat jij - ja jij - dus hoogstwaarschijnlijk ook besmet bent met dit virus. Maar er is nog geen reden tot paniek. Voor een lange tijd werd HHV-7 beschouwd als een onschadelijk virus, dat in enkele uitzonderlijke gevallen uitslag kan veroorzaken bij kinderen, roseola infantum genaamd. Het virus zit het liefst in de witte bloedcellen van je immuunsysteem, waar het al redelijk snel in slaap valt en ongevaarlijk wordt.
Correlatie of causaliteit?
Voor sommige mensen, zoals immuungecompromitteerde personen die leven met HIV/AIDS of net een orgaantransplantatie hebben ondergaan, is dit virus wel gevaarlijk. Wanneer je immuunsysteem verzwakt, wordt HHV-7 weer wakker en kan het ernstige ziektes veroorzaken, zoals ontstekingen en afstotingen van het getransplanteerde orgaan. Er komt ook steeds meer en meer bewijs dat HHV-7 niet zo onschadelijk is in gezonde mensen. Zelfs in gezonde mensen kan HHV-7 lijden tot koorts, luchtwegaandoeningen, oogzenuwontsteking, braken, diarree, en zelfs hersenontsteking. Maar de meningen zijn verdeeld of HHV-7 daadwerkelijk de dader is, of maar een onschuldige toeschouwer. Dit wordt ook niet geholpen door het feit dat zoveel mensen besmet zijn met HHV-7, dat je het altijd wel zal terugvinden in een ziek persoon.
De aanzet tot ons onderzoek
Ondanks dat de rol van HHV-7 onduidelijk is, raakt het wel steeds meer betrokken bij gevallen van ernstigere ziektes, zoals koorstuipen, hersenontsteking, en zelfs verlammingen. HHV-7 zou een mogelijke oorzaak kunnen zijn, maar het is nog niet duidelijk hoe. Deze ziektes zijn voornamelijk neurologisch en hebben dus te maken met ons zenuwstelsel. Onderzoekers hebben het virus in hersenweefsel gedetecteerd, wat extra bewijs geeft voor deze link tussen HHV-7 en neurologische aandoeningen. Hoewel deze verbanden nog zwak zijn, roepen ze intrigerende vragen op over de impact van het virus op het zenuwstelsel. Toch blijft het onduidelijk of HHV-7 inderdaad zenuwcellen kan infecteren. En deze vraag was de aanzet tot mijn masterthesis, waarin ik een manier wilde vinden om makkelijk te zien welke cellen (zenuwcellen, huidcellen, bloedcellen, …) HHV-7 allemaal kan binnendringen.
Onder de loep
Dan kwam de grote vraag: hoe ga ik dit aanpakken? Virussen zijn namelijk zo klein, dat je hele speciale apparatuur nodig hebt om ze te kunnen zien. Gelukkig is er nu een revolutionaire techniek om snel en goedkoop veranderingen aan te brengen in het DNA van virussen: CRISPR/Cas9. Met behulp van deze techniek heb ik, samen met andere wetenschappers van het HIV Cure Research Center in Gent, virussen gemaakt die een rood fluorescent eiwit permanent hebben ingebouwd in hun partikels, waardoor ze rood licht gaan uitstralen en dus makkelijker te zien zijn onder een fluorescentiemicroscoop. Zodoende, als wij onze rode virussen zouden loslaten op verschillende soorten cellen, en wij kunnen onder de microscoop rode stipjes zien binnen de cellen, kunnen we besluiten dat het virus deze cellen kan binnen dringen. Wanneer we een toename zien in het aantal rode virussen binnen deze cellen, kunnen we ervan uitgaan dat het virus zich ook kan vermenigvuldigen binnen de cellen. Als we dit zouden zien in zenuwcellen, geeft dat al wat meer argumenten voor de rol van HHV-7 in sommige gevallen van hersenontsteking of andere zenuwziektes.
Resultaten
De beste manier om rode virussen te maken, is om het rode eiwit vast te laten hangen aan een eiwit waar het virus niet zonder kan leven. Ik heb gekozen voor eiwitten die nodig zijn voor de structuur van het virus, en dus altijd aanwezig zijn. Onder een fluorescentiemicroscoop kan je het rode licht zien met behulp van een groene laser. Het eiwit neemt het groene licht op en straalt rood licht weer terug uit. Deze fluorescerende virussen werden eerst gebruikt om te kijken of ze SupT1 cellen, die heel erg lijken om je eigen immuuncellen maar veel langer leven, kunnen binnendringen. En zoals verwacht, zag ik mooie rode bolletjes verschijnen van cellen gevuld met HHV-7 (afbeelding 1. Boven). Daarna heb ik geprobeerd een andere celsoort te infecteren: HEK293T cellen. Dit zijn een soort niercellen, die ook mooi rood kleurden nadat HHV-7 ze had binnengedrongen (afbeelding 1. Onder). Dit bewijst dat HHV-7 zowel een soort witte bloedcellen als niercellen kan infecteren, wat kan helpen in het ontrafelen van bepaalde ziektes.
Afbeelding 1. Boven: witte bloedcellen die door rode HHV-7 partikels zijn geïnfecteerd. Onder: niercellen die door de rode HHV-7 partikels zijn geïnfecteerd. De HHV-7 infectie in deze cellen kan aanleiding geven tot bepaalde ziektes.
Voor de toekomst
Deze rode virussen zijn het begin van een heel interessant onderzoek naar het potentieel van HHV-7 als dader in vele verschillende ziektes. De volgende stap zou het infecteren zijn van zenuwcellen met het rode HHV-7, om te zien wat nu de rol is van HHV-7 in niet alleen hersenontsteking, maar ook andere zenuwziektes. Op deze manier zal HHV-7 niet lang meer mysterieus blijven.
Conclusie
Humaan herpesvirus type 7, een wijdverspreide maar verborgen ziekteverwekker, blijft wetenschappers en medische experts verbijsteren. Naarmate de rol ervan bij verschillende ziekten duidelijker wordt, neemt de nood toe om te begrijpen hoe een HHV-7 precies in elkaar zit. Onderzoeksinspanningen moeten worden voortgezet om licht te werpen op het raadsel van HHV-7, de mysteries ervan te ontrafelen en de weg vrij te maken voor verbeterde diagnostiek, behandelingen en uiteindelijk betere gezondheidsresultaten voor iedereen.
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