Viral induction of site‐specific chromosome damage
- 19 December 2002
- journal article
- review article
- Published by Wiley in Reviews in Medical Virology
- Vol. 13 (1), 21-37
- https://doi.org/10.1002/rmv.368
Abstract
The advent of advanced cell culture and cytogenetics techniques in the 1950s opened a new avenue for research on the pathogenic interactions between animal viruses and their hosts. Studies of many viruses revealed their ability to nonspecifically induce cytogenetic damage to their host cell's chromosomes. However, only three viruses, the oncogenic adenoviruses, herpes simplex virus (HSV) and human cytomegalovirus (HCMV), have been found to cause non‐random, site‐specific chromosomal damage. Adenovirus (Ad) type 12 induces fragility at four distinct loci (RNU1, RNU2, RN5S and PSU1) in many different types of human cells. A common feature of these loci is that they contain a repeated array of transcriptionally active genes encoding small structural RNAs. Site‐specific induction of breaks also requires the virally encoded E1B protein of Mr 55 000 and the C‐terminus of the cellular p53 protein. Analysis of the induction of damage by HSV and HCMV necessitates consideration of several factors, including the strain of virus used, the timing of infection, the type of cell used, and the multiplicity of infection. Both HSV strains 1 and 2 are cytotoxic, although the former seems to be more proficient at inducing damage. At early times post infection, HSV induces breaks and specific uncoiling of the centromeres of chromosomes 1, 9 and 16. This is followed at later times by a more complete severing of all of the chromosomes, termed pulverisation. Damage by HSV requires viral entry and de novo viral protein synthesis, with immediate early viral proteins responsible for the induction of breaks and uncoiling and early gene products (most likely nucleases) involved in the extensive pulverisation seen later. HCMV has been studied primarily in permissive human fibroblasts. Its ability to induce specific damage in chromosome 1 at two loci, 1q21 and 1q42, was only recently revealed as the cells must be in S‐phase when they are infected for the breaks to be observed. In contrast to adenovirus and HSV, HCMV induction of specific breakage requires only viral entry into the cell and not de novo viral protein expression. This latter point may be a factor in its ability to cause damage in the developing fetal brain, where the most severe clinical manifest ations of congenital infection are observed. Copyright © 2003 John Wiley & Sons, Ltd.Keywords
This publication has 77 references indexed in Scilit:
- Infection of Cells with Human Cytomegalovirus during S Phase Results in a Blockade to Immediate-Early Gene Expression That Can Be Overcome by Inhibition of the ProteasomeJournal of Virology, 2002
- Early induction of DNA single-stranded breaks in cells infected by herpes simplex virus type 1Archiv für die gesamte Virusforschung, 1992
- Fluorescence in situ mapping of the human nuclear NAD+ ADP-ribosyltransferase gene (ADPRT) and two secondary sites to human chromosomal bands 1q42, 13q34, and 14q24Cytogenetic and Genome Research, 1992
- Herpes simplex virus gene products involved in the induction of chromosomal aberrationsVirus Research, 1986
- The gene cluster for human U2 RNA is located on chromosome 17q21Experimental Cell Research, 1985
- Adenovirus 12 uncoiler regions of human chromosome 1 in relation to the 5S rRNA genesExperimental Cell Research, 1976
- Herpes viruses and chromosomal alterations seen with light and whole-mount electron microscopyExperimental Cell Research, 1972
- Adenovirus-induced Chromosome Aberrations in Human CellsJournal of General Virology, 1971
- Chromosome Changes in Human Cells induced by Herpes Simplex, Types 1 and 2Nature, 1969
- Viruses and mammalian chromosomes chromosome aberrations by human adenovirus type 12Experimental Cell Research, 1964