Induction of PERV antigen in porcine peripheral blood mononuclear cells by human herpesvirus 1

• Published in: Xenotransplantation (Københaven) Vol. 22; no. 2; pp. 144 - 150
• Main Authors: Kim, Jiyeon, Kim, Jung Heon, Hwang, Eung Soo
• Format: Journal Article
• Language: English
• Published: Denmark Blackwell Publishing Ltd 01.03.2015
• Subjects: Animals; Antigens, Viral - biosynthesis; Cell Line; Coinfection - immunology; Coinfection - virology; Endogenous Retroviruses - immunology; Endogenous Retroviruses - pathogenicity; Enzyme-Linked Immunosorbent Assay - methods; Gag; Gene Products, gag - biosynthesis; Gene Products, gag - immunology; HEK293 Cells; Herpesvirus 1, Human - pathogenicity; Heterografts - virology; human herpesvirus; Human herpesvirus 1; Humans; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - virology; porcine cells; Porcine endogenous retrovirus; Swine - virology; Swine, Miniature; Transplantation, Heterologous - adverse effects; xenotransplantation; xenotransplantation; human herpesvirus; porcine endogenous retrovirus; Gag; porcine cells
• ISSN: 0908-665X; 1399-3089; 1399-3089
• DOI: 10.1111/xen.12160

Background Xenotransplantation represents one of alternative candidates for allotransplantation due to the chronic shortage of suitable human tissues; however, many obstacles remain. Expression and release of endogenous retroviral antigens by porcine cells after transplantation may evoke adverse immune responses in human subjects. Here, we examined whether human herpesvirus 1 (HHV‐1) could induce the production of porcine endogenous retrovirus (PERV) antigens in porcine peripheral blood mononuclear cells (PBMCs). Methods Porcine PBMCs were infected with HHV‐1 and examined for the production of PERV Gag protein and HHV‐1 using antigen‐capture ELISA and quantitative real‐time polymerase chain reaction (PCR), respectively. Results HHV‐1 infection resulted in a 1.7‐ to 33.2‐fold induction of PERV Gag relative to mock infection controls, compared to a 2.9‐ to 12.9‐fold induction following treatment with PMA. Expression of PERV Gag was detected in porcine PBMCs and PK‐15 cells after HHV‐1 infection by double immunofluorescence staining of PERV Gag and HHV‐1 antigen. The viability of HHV‐1‐infected porcine PBMCs was significantly lower than that of mock‐infected cells. The HHV‐1 level in the culture supernatant increased 5.2‐fold relative to controls 24‐h post‐infection, indicative of active replication within these cells; decreased levels of HHV‐1 were detected 72‐h post‐infection. Conclusions These results suggest that HHV‐1 may be capable of infecting transplanted porcine cells, resulting in strong direct induction of PERV antigen.