Department of Microbiology and Virology, Faculty of Natural Sciences, Comenius University, Ilkovicova 6, Mlynska dolina B2, 84215 Bratislava, Slovakia.
Institute of Virology, Biomedical Research Center of the Slovak Academy of Sciences, Dubravska cesta 9, 84505 Bratislava, Slovakia.
Pathog Dis. 2023 Jan 17;81. doi: 10.1093/femspd/ftad004.
Murine herpesvirus 68 (MHV-68) belongs to the subfamily Gammaherpesvirinae of the family Herpesviridae. This exceptional murine herpesvirus is an excellent model for the study of human gammaherpesvirus infections. Cells infected with MHV-68 under nonpermissive conditions for viral replication produce substances designated as MHV-68 growth factors (MHGF-68), that can cause transformation of the cells, or on the other side, turn transformed cells into normal. It was already proposed, that the MHGF-68 fractions cause transformation, disruption of the cytoskeleton and slower growth of the tumors in nude mice. Here, we examined newly extracted fractions of MHGF-68 designated as F5 and F8. Both fractions proved to inhibit the growth of the spheroids and also tumours induced in nude mice. What more, the fractions caused the decrease of the protein levels of wt p53 and HIF-1α. Decreased levels of p53 and HIF-1α activity leads to decreased vascularization, slower tumour growth, and lower adaptation to hypoxic conditions. This would propose MHGF-68 fractions, or their human herpesvirus equivalents, as a potential anticancer drugs in combined chemotherapy.
鼠疱疹病毒 68（MHV-68）属于疱疹病毒科疱疹病毒亚科。这种特殊的鼠疱疹病毒是研究人类γ疱疹病毒感染的极好模型。在不允许病毒复制的条件下感染 MHV-68 的细胞会产生被称为 MHV-68 生长因子（MHGF-68）的物质，这些物质可以导致细胞转化，或者将转化细胞转化为正常细胞。已经有人提出，MHGF-68 分数会导致转化、细胞骨架破坏和裸鼠中肿瘤生长缓慢。在这里，我们检查了新提取的 MHGF-68 级分 F5 和 F8。这两种级分都被证明可以抑制球体和裸鼠诱导的肿瘤的生长。更重要的是，这些级分导致 wt p53 和 HIF-1α 蛋白水平降低。p53 和 HIF-1α 活性的降低会导致血管生成减少、肿瘤生长缓慢和对低氧条件的适应能力降低。这将表明 MHGF-68 级分或其人类疱疹病毒等效物作为联合化疗中的潜在抗癌药物。
