In:
Xenotransplantation, Wiley, Vol. 13, No. 3 ( 2006-05), p. 258-263
Abstract:
Miyagawa S, Nakatsu S, Hazama K, Nakagawa T, Kondo A, Matsunami K, Yamamoto A, Yamada J, Miyazawa T, Shirakura R. A novel strategy for preventing PERV transmission to human cells by remodeling the viral envelope glycoprotein. Xenotransplantation 2006; 13: 258–263. © Blackwell Munksgaard, 2006 Abstract: Background: Porcine endogenous retrovirus (PERV) released from pig cells is a main problem associated with clinical xenotransplantation. In a previous study, we demonstrated that the high mannose type of N ‐glycan of the envelope glycoprotein is closely related to PERV infectivity with respect to human cells. In this study, we addressed the effects of reducing the high mannose type of N ‐glycan on PERV infectivity. Methods: Pig endothelial cells (PEC) were transduced with the LacZ gene by a pseudotype infection to produce PEC( Z ). The PEC( Z )s were then further infected with PERV subtype B (PERV‐B) to produce PEC( Z )/PB. The PEC( Z )/PBs were next transfected with the α 1,2 mannosidase Ib (Man Ib), N‐acetylglucosaminyltransferase I (GnT‐I) or α ‐mannosidase II (Man II) gene in order to reduce the levels of high mannose type of N ‐glycan. HEK293 cells were inoculated with the PERV in each of the culture supernatants. The inoculated cells were histochemically stained and the LacZ ‐positive cells were counted. Results: In experiment I, PERV transmission from the PEC( Z )/PB with GnT‐I or Man II to HEK 293 cells was significantly reduced in comparison with control PEC( Z )/PB, while the PEC( Z )/PB with Man Ib was not. However, in experiment II, PERV transmission from the PEC( Z )/PB with ManIb to HEK 293 cells was also significantly reduced in comparison with control PEC( Z )/PB. Conclusion: The transfection of these genes to pig cells is effective in reducing the susceptibility of human cells to PERV infection. The results suggest that this represents a potentially useful strategy for further decreasing the likelihood of PERV infections.
Type of Medium:
Online Resource
ISSN:
0908-665X
,
1399-3089
DOI:
10.1111/xen.2006.13.issue-3
DOI:
10.1111/j.1399-3089.2006.00313.x
Language:
English
Publisher:
Wiley
Publication Date:
2006
detail.hit.zdb_id:
2011995-1
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