Mueller Nicolas J, Sulling Kristen, Gollackner Bernd, Yamamoto Shin, Knosalla Christoph, Wilkinson Robert A, Kaur Amitinder, Sachs David H, Yamada Kazuhiko, Cooper David K C, Patience Clive, Fishman Jay A
Infectious Diseases Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Am J Transplant. 2003 Sep;3(9):1057-64. doi: 10.1034/j.1600-6143.2003.00192.x.
In pig-to-baboon xenotransplantation, porcine cytomegalovirus (PCMV) causes viremia, consumptive coagulopathy, and tissue-invasive disease. Baboon cytomegalovirus (BCMV) is associated with invasive disease in xenograft recipients. The efficacy of prophylaxis with intravenous ganciclovir (GCV) was studied for prevention of PCMV and BCMV infections in pig-to baboon xenotransplantation. GCV prophylaxis did not alter the incidence of BCMV activation in recipients, but reduced the amount of virus in tissues (mean 8.38 x 10(2) vs. 3.24 x 10(5) copies/ micro g DNA without treatment) and prevented tissue-invasive infections. PCMV viral loads were unaltered by GCV prophylaxis (8.36 x 10(8) copies/ micro g DNA without prophylaxis vs. 1.20 x 10(9) copies/ micro g DNA with prophylaxis). In vitro, PCMV was relatively resistant to GCV [90% inhibitory concentration (IC90) of 10 micro m, IC50 = 3 micro m], acyclovir (100 micro m), and leflunomide (not achievable). Only cidofovir (IC90 1 micro m) and foscarnet (IC90 100 micro m) might have therapeutic efficacy for PCMV in vivo in achievable concentrations, although these agents often carry significant toxicity in transplant recipients. GCV has limited activity against BCMV and no therapeutic efficacy against PCMV at standard doses in vivo. GCV and other antiviral agents have limited activities against PCMV in vitro. Breeding of PCMV-free xenograft donors may be necessary to prevent PCMV infections in clinical trials.
在猪到狒狒的异种移植中，猪巨细胞病毒（PCMV）可引起病毒血症、消耗性凝血病和组织侵袭性疾病。狒狒巨细胞病毒（BCMV）与异种移植受者的侵袭性疾病有关。研究了静脉注射更昔洛韦（GCV）预防猪到狒狒异种移植中PCMV和BCMV感染的疗效。GCV预防并未改变受者中BCMV激活的发生率，但减少了组织中的病毒量（未治疗时平均为8.38×10²拷贝/μg DNA，治疗后为3.24×10⁵拷贝/μg DNA），并预防了组织侵袭性感染。GCV预防对PCMV病毒载量无影响（未预防时为8.36×10⁸拷贝/μg DNA，预防后为1.20×10⁹拷贝/μg DNA）。在体外，PCMV对GCV[90%抑制浓度（IC90）为10μm，IC50 = 3μm]、阿昔洛韦（100μm）和来氟米特（无法达到）相对耐药。只有西多福韦（IC90 1μm）和膦甲酸钠（IC90 100μm）在可达到的浓度下可能对体内PCMV有治疗效果，尽管这些药物在移植受者中通常具有显著毒性。GCV对BCMV的活性有限，在体内标准剂量下对PCMV无治疗效果。GCV和其他抗病毒药物在体外对PCMV的活性有限。在临床试验中，可能需要培育无PCMV的异种移植供体以预防PCMV感染。
