Hoc protein regulates the biological effects of T4 phage in mammals

• Published in: Archives of microbiology Vol. 187; no. 6; pp. 489 - 498
• Main Authors: Dabrowska, Krystyna, Zembala, Maria, Boratynski, Janusz, Switala-Jelen, Kinga, Wietrzyk, Joanna, Opolski, Adam, Szczaurska, Katarzyna, Kujawa, Marek, Godlewska, Joanna, Gorski, Andrzej
• Format: Journal Article
• Language: English
• Published: Heidelberg Berlin/Heidelberg : Springer-Verlag 01.06.2007; Berlin Springer; Springer Nature B.V
• Subjects: Animals; Antibacterial activity; Antiinfectives and antibacterials; Antineoplastic Agents - pharmacology; Bacteriology; Bacteriophage HAP1; Bacteriophage T4; Bacteriophage T4 - classification; Bacteriophage T4 - genetics; Bacteriophage T4 - physiology; Bacteriophage T4 - ultrastructure; Biological and medical sciences; Biological effects; Cancer; Capsid Proteins - genetics; Capsid Proteins - metabolism; Electrophoretic mobility; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Viral; Hoc protein; Ionic strength; Liver; Male; Mammals; Melanoma; Melanoma, Experimental - secondary; Melanoma, Experimental - therapy; Melanoma, Experimental - virology; Metastases; Mice; Mice, Inbred C57BL; Microbiology; Miscellaneous; Muscles; Mutants; Mutation; Organ Specificity; Phages; Proteins; Spleen; Tumors; Viral Proteins - genetics; Viral Proteins - metabolism; Virology; Virus; T even phage; Vertebrata; Regulation(control); Mammalia; Hoc protein; Myoviridae; Protein; Bacteriophage T4, Bacteriophage HAP1; Phage; Phage T4
• ISSN: 0302-8933; 1432-072X
• DOI: 10.1007/s00203-007-0216-y

We previously investigated the biological, non-antibacterial effects of bacteriophage T4 in mammals (binding to cancer cells in vitro and attenuating tumour growth and metastases in vivo); we selected the phage mutant HAP1 that was significantly more effective than T4. In this study we describe a non-sense mutation in the hoc gene that differentiates bacteriophage HAP1 and its parental strain T4. We found no substantial effects of the mutation on the mutant morphology, and its effects on electrophoretic mobility and hydrodynamic size were moderate. Only the high ionic strength of the environment resulted in a size difference of about 10 nm between T4 and HAP1. We compared the antimetastatic activity of the T2 phage, which does not express protein Hoc, with those of T4 and HAP1 (B16 melanoma lung colonies). We found that HAP1 and T2 decreased metastases with equal effect, more strongly than did T4. We also investigated concentrations of T4 and HAP1 in the murine blood, tumour (B16), spleen, liver, or muscle. We found that HAP1 was rapidly cleared from the organism, most probably by the liver. Although HAP1 was previously defined to bind cancer cells more effectively (than T4), its rapid elimination precluded its higher concentration in tumours.