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Göteborgs universitets publikationer

Virus-induced appearance of the selectin ligand sLeX in herpes simplex virus type 1-infected T cells: Involvement of host and viral factors.

Författare och institution:
Rickard Nordén (Institutionen för biomedicin, avdelningen för infektionssjukdomar); Kristina Nyström (Institutionen för biomedicin, avdelningen för infektionssjukdomar); Johan Aurelius (Institutionen för biomedicin, avdelningen för infektionssjukdomar); Mikael Brisslert (Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning); Sigvard Olofsson (Institutionen för biomedicin)
Publicerad i:
Glycobiology, 23 ( 3 ) s. 310-321
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
Circulating leukocytes that express selectin ligands such as the carbohydrate epitope sialyl Lewis X (sLeX) may interact with endothelial selectins, resulting in transmigration of the leukocyte across the endothelial wall to adjacent tissue. Due to the potential of selectin-ligand interactions as targets in viral pathogenesis, we aimed at determining whether herpes simplex virus type 1 (HSV1) is able to induce appearance of sLeX at the surface of infected leukocytes. We found that HSV1 infection of a T cell line resulted in transcriptional activation of human fucosyltransferase genes FUT3, FUT6 and FUT7, the two latter genes encoding fucosyltransferases rate limiting for sLeX synthesis. Flow cytometry and confocal microscopy demonstrated that HSV1 infection resulted in a two-fold rise in the proportion of sLeX-positive cells. Increased levels of FUT3, FUT6 and FUT7 RNA were detected already at 3 h post infection, and treatment with cycloheximide, a translation inhibitor, blocked HSV1-induced increase in expression of FUT3, FUT6 and FUT7 RNA, suggesting involvement of viral or cellular proteins. Studies with infectious viral mutants indicated that the viral immediate early (α) protein ICP0 is essential for initiation of FUT7 though not for FUT3 or FUT6 transcription. In CD3+ cells, derived from peripheral blood mononuclear cells, HSV1 infection induced expression of FUT3, FUT5 and FUT6, whereas FUT7 was not altered. The mean sLeX fluorescence intensity of CD3+ cells was significantly higher in HSV1-infected CD3+ cells. This suggests that infected leukocytes during HSV1 viremia may express selectin ligands with possible but as yet unproven roles in viral pathogenesis.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Annan medicin och hälsovetenskap
FUT6/FUT7, herpesvirus, selectin ligands, sialyl Lewis X
Postens nummer:
Posten skapad:
2012-12-18 09:05
Posten ändrad:
2013-03-05 08:23

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