Human cytomegalovirus (HCMV) components are often found in tumors, but the precise relationship between HCMV and cancer remains a matter of debate. Pro-tumor functions of HCMV were described in several studies, but an association between HCMV seropositivity and reduced cancer risk was also evidenced, presumably relying on recognition and killing of cancer cells by HCMV-induced lymphocytes. This study aimed at deciphering whether CMV influences cancer development in an immune-independent manner. Using immunodeficient mice, we showed that systemic infection with murine CMV (MCMV) inhibited the growth of murine carcinomas. Surprisingly, MCMV, but not HCMV, also reduced human colon carcinoma development in vivo. In vitro, both viruses infected human cancer cells. Expression of human interferon-β (IFN-β) and nuclear domain (ND10) were induced in MCMV-infected, but not in HCMV-infected human colon cancer cells. These results suggest a decreased capacity of MCMV to counteract intrinsic defenses in the human cellular host. Finally, immunodeficient mice receiving peri-tumoral MCMV therapy showed a reduction of human colon cancer cell growth, albeit no clinical sign of systemic virus dissemination was evidenced. Our study, which describes a selective advantage of MCMV over HCMV to control human colon cancer, could pave the way for the development of CMV-based therapies against cancer.

人巨细胞病毒（HCMV）成分通常在肿瘤中发现，但是HCMV与癌症之间的确切关系仍存在争议。几项研究描述了HCMV的促肿瘤功能，但也证实了HCMV血清阳性与降低癌症风险之间的关联，大概是依靠HCMV诱导的淋巴细胞识别和杀死癌细胞。这项研究旨在破译CMV是否以免疫独立的方式影响癌症的发展。使用免疫缺陷小鼠，我们显示了鼠CMV（MCMV）的全身感染抑制了鼠癌的生长。出人意料的是，MCMV而非HCMV也减少了人结肠癌在体内的发展。体外，这两种病毒都感染人类癌细胞。在MCMV感染的人结肠癌细胞中诱导了人干扰素-β（IFN-β）和核结构域（ND10）的表达，但在HCMV感染的人结肠癌细胞中未诱导。这些结果表明，MCMV抵抗人类细胞宿主内在防御的能力降低。最后，尽管没有证据表明全身性病毒传播的临床迹象，但接受肿瘤周围MCMV疗法的免疫缺陷小鼠表现出人类结肠癌细胞生长减少。我们的研究描述了MCMV在控制人结肠癌方面优于HCMV的选择性优势，这可能为基于CMV的抗癌疗法的发展铺平道路。