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Polyamine biosynthesis in cells infected with different clinical isolates of human cytomegalovirus
1Department of Medical Microbiology, St. Mary's Hospital Medical School, Paddington, London, England.
Abstract:
Previous work in this laboratory showed that polyamine biosynthesis was stimulated in fibroblasts following infection with the AD169 strain of human cytomegalovirus (HCMV) or with murine cytomegalovirus (MCMV) (Tyms et al: Biophysics Research Communications 86:312-318, 1979; Advances in Polyamine Research 4:507-517, 1983). Here we compare the affect of AD169 on polyamine production in infected fibroblasts with that of the unusual Colburn strain of HCMV. The Colburn virus is unusual in that it was isolated from a 7 year old boy with encephalitis and molecular studies indicated the virus was simian like (Huang et al: Journal of Virology 26:718-723, 1978). As a consequence of CMV infection a two to ten fold increase in the spermine content of fibroblast cells is observed. Radiolabel transfer experiments show that spermine is synthesized throughout virus infection. Indeed, spermidine and spermine are specifically incorporated into the purified virions of the AD169 and Colburn strains of HCMV. Furthermore, polyamine biosynthesis is stimulated in fibroblast cells infected with a number of low passage clinical isolates of HCMV. Inhibition of polyamine biosynthesis in HCMV infection may provide a specific and novel target for antiviral chemotherapy.
Insights
Human cytomegalovirus (HCMV) infection significantly increases polyamine production in fibroblasts, with spermine incorporated into viral particles. This suggests targeting polyamine biosynthesis could be a novel antiviral strategy.
Area of Science:
- Virology
- Molecular Biology
- Biochemistry
Background:
- Previous studies indicated polyamine biosynthesis is stimulated by human cytomegalovirus (HCMV) and murine cytomegalovirus (MCMV).
- The Colburn strain of HCMV is unusual, isolated from a child with encephalitis and exhibiting simian-like characteristics.
Purpose of the Study:
- To compare the effects of the AD169 and Colburn strains of HCMV on polyamine production in infected fibroblasts.
- To investigate the role of polyamines in HCMV replication and their potential as antiviral targets.
Main Methods:
- Fibroblast cell cultures infected with AD169 and Colburn HCMV strains.
- Measurement of polyamine content (spermine, spermidine) using radiolabel transfer experiments.
- Analysis of polyamine incorporation into purified HCMV virions.
Main Results:
- HCMV infection caused a two to ten-fold increase in fibroblast spermine content.
- Spermine synthesis occurred throughout the infection cycle.
- Spermidine and spermine were specifically incorporated into AD169 and Colburn HCMV virions.
- Polyamine biosynthesis was also stimulated by other clinical HCMV isolates.
Conclusions:
- HCMV infection profoundly affects cellular polyamine metabolism.
- Polyamines are essential components of HCMV virions.
- Inhibiting polyamine biosynthesis presents a promising novel target for HCMV antiviral chemotherapy.