Infectious Disease Division and MGH Transplant Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Columbia Center for Translational Immunology, Departments of Medicine and Surgery, Columbia University, New York, NY, USA.
Xenotransplantation. 2018 Sep;25(5):e12395. doi: 10.1111/xen.12395. Epub 2018 Apr 6.
Studies of xenotransplantation from swine have identified porcine viruses as potential barriers to clinical trials. The biology of these viruses has not been extensively investigated in the in vivo xeno-environment. Enhancement of viral gene expression by viral and cellular factors acting in trans has been demonstrated for certain viruses, including bidirectional interactions between human herpesviruses and endogenous (HERV) and exogenous (HIV) retroviruses. Both porcine cytomegalovirus (PCMV) and porcine endogenous retrovirus (PERV) infections have been identified in xenografts from swine. PERV receptors exist on human cells with productive infection in vitro in permissive human target cell lines. PCMV is largely species-specific with infection restricted to the xenograft in pig-to-baboon transplants. It is unknown whether coinfection by PCMV affects the replication of PERV within xenograft tissues which might have implications for the risk of retroviral infection in the human host.
A series of 11 functioning, life-supporting pig-to-baboon kidney xenografts from PERV-positive miniature swine were studied with and without PCMV co-infection. Frozen biopsy samples were analyzed using quantitative, real-time PCR with internal controls.
PERV replication was not altered in the presence of PCMV coinfection (P = .70). The absence of variation with coinfection was confirmed when PERV quantitation was expressed relative to simultaneous cellular GAPDH levels with or without PCMV coinfection (P = .59).
PCMV coinfection does not alter the replication of PERV in life-supporting renal xenotransplantation in vivo in baboons.
从猪进行异种移植的研究已经确定了猪病毒作为临床试验的潜在障碍。这些病毒的生物学在体内异种环境中尚未得到广泛研究。某些病毒的病毒和细胞因子的反式作用增强了病毒基因的表达，包括人类疱疹病毒和内源性（HERV）和外源性（HIV）逆转录病毒之间的双向相互作用。在来自猪的异种移植物中已经鉴定出猪巨细胞病毒（PCMV）和猪内源性逆转录病毒（PERV）感染。PERV 受体存在于具有体外在允许的人类靶细胞系中产生感染的人类细胞上。PCMV 主要是种特异性的，感染仅限于猪到狒狒移植中的异种移植物。尚不清楚 PCMV 共同感染是否会影响 PERV 在异种组织中的复制，这可能对人类宿主中逆转录病毒感染的风险产生影响。
研究了一系列来自 PERV 阳性迷你猪的 11 个功能齐全、维持生命的猪到狒狒肾异种移植，有无 PCMV 合并感染。使用定量实时 PCR 并使用内部对照对冷冻活检样本进行分析。
PCMV 合并感染时 PERV 复制没有改变（P=0.70）。当 PERV 定量表达相对于同时存在或不存在 PCMV 合并感染的细胞 GAPDH 水平时，合并感染时没有变化得到确认（P=0.59）。
PCMV 合并感染不会改变体内在支持生命的肾异种移植中 PERV 的复制。
