Murine herpesvirus-68-related growth factors treatment correlates with decrease of p53 and HIF-1α protein levels

Abstract 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 replicati...

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Bibliographic Details
Published in:Pathogens and disease 2023-01, Vol.81
Main Authors: Supolikova, Miroslava, Novakova, Eva, Donatova, Karin, Olejnikova, Petra, Labudova, Martina
Format: Article
Language:English
Subjects:
Animals
Antineoplastic drugs
Chemotherapy
Cytoskeleton
Gammaherpesvirinae
Growth factors
Herpes viruses
Herpesviridae Infections - drug therapy
Herpesviridae Infections - pathology
Humans
Hypoxia
Hypoxia-inducible factor 1a
Mice
Mice, Nude
Neoplasms
p53 Protein
Proteins
Rhadinovirus
Spheroids
Transformed cells
Tumor Suppressor Protein p53
Tumors
Vascularization
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Summary:Abstract 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. The MHGF68 fractions treatment is accompanied by the lower expression of p53 and HIF-1α proteins, that leads to slower growth of tumours.
ISSN:2049-632X
2049-632X
DOI:10.1093/femspd/ftad004