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Miyagawa, S. et al.

Miyagawa, Nakatsu, Hazama, Nakagawa, Kondo, Matsunami, Yamamoto, Yamada, Miyazawa, Shirakura,

A novel strategy for preventing PERV transmission to human cells by remodeling the viral envelope glycoprotein.

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 alpha 1,2 mannosidase Ib (Man Ib), N-acetylglucosaminyltransferase I (GnT-I) or alpha-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.[1]

References

A novel strategy for preventing PERV transmission to human cells by remodeling the viral envelope glycoprotein. Miyagawa, S., Nakatsu, S., Hazama, K., Nakagawa, T., Kondo, A., Matsunami, K., Yamamoto, A., Yamada, J., Miyazawa, T., Shirakura, R. Xenotransplantation (2006) [Pubmed]

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