U94 of human herpesvirus 6 is expressed in latently infected peripheral blood mononuclear cells and blocks viral gene expression in transformed lymphocytes in culture

U94 of human herpesvirus 6 is expressed in latently infected peripheral blood mononuclear cells and blocks viral gene expression in transformed lymphocytes in culture

^*Department of Experimental and Diagnostic Medicine, Section of Microbiology, University of Ferrara, Via Borsari, 44100 Ferrara, Italy; and ^‡Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642

Edited by Bernard Roizman, The University of Chicago, Chicago, IL, and approved September 15, 1998 (received for review July 16, 1998)

Abstract

Human herpesvirus 6 (HHV-6) like other herpesviruses, expresses sequentially immediate early (IE), early, and late genes during lytic infection. Evidence of ability to establish latent infection has not been available, but by analogy with other herpesviruses it could be expected that IE genes that regulate and transactivate late genes would not be expressed. We report that peripheral blood mononuclear cells of healthy individuals infected with HHV-6 express the U94 gene, transcribed under IE conditions. Transcription of other IE genes (U16/17, U39, U42, U81, U89/90, U91) was not detected. To verify that U94 may play a role in the maintenance of the latent state, we derived lymphoid cell lines that stably expressed U94. HHV-6 was able to infect these cells, but viral replication was restricted. No cytopathic effect developed. Furthermore, viral transcripts were present in the first days postinfection and declined thereafter. A similar decline in the level of intracellular viral DNA also was observed. These findings are consistent with the hypothesis that the U94 gene product of HHV-6 regulates viral gene expression and enables the establishment and/or maintenance of latent infection in lymphoid cells.

Footnotes

↵ † A.R. and T.R. contributed equally to this work.
↵ § To whom reprint requests should be addressed at: Department of Experimental and Diagnostic Medicine, Section Microbiology, University of Ferrara, Via Borsari 46, 44100 Ferrara, Italy. e-mail: dil{at}dns.unife.it.
This paper was submitted directly (Track II) to the Proceedings Office.
ABBREVIATIONS:

PBMC,

peripheral blood mononuclear cell;

HHV,

human herpesvirus;

HSV,

herpes simplex virus;

IE,

immediate early;

LAT,

HSV latency-associated transcript;

RT-PCR,

reverse transcription–PCR