小鼠疱疹病毒-68相关生长因子治疗与p53和HIF-1α蛋白水平降低相关。

IF 2.7 4区 医学 Q3 IMMUNOLOGY Pathogens and disease Pub Date : 2023-01-17 DOI:10.1093/femspd/ftad004
Miroslava Supolikova, Eva Novakova, Karin Donatova, Petra Olejnikova, Martina Labudova
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引用次数: 0

摘要

鼠疱疹病毒68 (MHV-68)属于疱疹病毒科γ疱疹病毒亚科。这种特殊的鼠疱疹病毒是研究人类伽玛疱疹病毒感染的一个极好的模型。在不允许病毒复制的条件下,被MHV-68感染的细胞产生被称为MHV-68生长因子(MHGF-68)的物质,这种物质可以引起细胞的转化,或者另一方面,将转化的细胞变为正常细胞。已经有人提出,MHGF-68部分会导致裸鼠肿瘤的转化、细胞骨架的破坏和肿瘤生长的减慢。在这里,我们检测了新提取的MHGF-68的F5和F8部分。这两种成分都被证明能抑制球体的生长,也能抑制裸鼠诱导的肿瘤。此外,各组分引起wt - p53和HIF-1α蛋白水平的降低。p53和HIF-1α活性水平的降低导致血管化减少,肿瘤生长减慢,对缺氧条件的适应能力降低。这将提出MHGF-68部分,或其人类疱疹病毒等同物,作为联合化疗中潜在的抗癌药物。
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Murine herpesvirus-68-related growth factors treatment correlates with decrease of p53 and HIF-1α protein levels.

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.

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来源期刊
Pathogens and disease
Pathogens and disease IMMUNOLOGY-INFECTIOUS DISEASES
CiteScore
7.40
自引率
3.00%
发文量
44
期刊介绍: Pathogens and Disease publishes outstanding primary research on hypothesis- and discovery-driven studies on pathogens, host-pathogen interactions, host response to infection and their molecular and cellular correlates. It covers all pathogens – eukaryotes, prokaryotes, and viruses – and includes zoonotic pathogens and experimental translational applications.
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