Recruitment of herpes simplex virus type 1 transcriptional regulatory protein ICP4 into foci juxtaposed to ND10 in live, infected cells

Everett, R.D., Sourvinos, G. and Orr, A. (2003) Recruitment of herpes simplex virus type 1 transcriptional regulatory protein ICP4 into foci juxtaposed to ND10 in live, infected cells. Journal of Virology, 77(6), pp. 3680-3689. (doi: 10.1128/jvi.77.6.3680-3689.2003)

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Publisher's URL: http://dx.doi.org/10.1128/jvi.77.6.3680-3689.2003

Abstract

At the early stages of herpes simplex virus type 1 (HSV-1) infection, parental viral genomes have a tendency to become juxtaposed to cellular nuclear structures known as PML (promyelocytic leukemia) nuclear bodies or ND10, while the immediate-early (IE) protein ICP0 precisely colocalizes with these structures. Previous indirect-immunofluorescence studies observed that the HSV-1 transcriptional regulator ICP4 has a mainly diffuse nuclear distribution early in infection and is later recruited into viral replication compartments. We have constructed HSV-1 variants expressing ICP4 and ICP0 linked to ECFP and EYFP, respectively, both singly and in combination. Coupled with an efficient method of expressing autofluorescent PML in ND10, we have studied the dynamics of ICP0, ICP4, and ND10 in live, infected cells. The greater sensitivity and lower background signals in live cells revealed that early in infection, ICP4 forms discrete foci, some of which are juxtaposed to ND10, while ICP0 was found to colocalize precisely with PML. As expected from these results, using a double-labeled virus, we observed that foci of ICP0 and ICP4 were also juxtaposed but not colocalized early in infection. Some of the ICP4 foci must have contained parental viral genomes, because they developed into replication compartments. We propose that a proportion of the ND10-associated ICP4 foci represent ICP4 molecules being recruited onto parental viral genomes, a process likely to be a critical step early in lytic infection. These results may be analogous to the localization of IE1 and IE2 during human cytomegalovirus infection, suggesting a principle common to the alpha- and betaherpesviruses.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Everett, Professor Roger and Orr, Mrs Anne
Authors: Everett, R.D., Sourvinos, G., and Orr, A.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:Journal of Virology
Journal Abbr.:J. Virol.
ISSN:0022-538X
ISSN (Online):1098-5514

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