Author/Editor		Trevisan, Marta; Matkovič, Urška; Cusinato, Riccardo; Toppo, Stefano; Palu, Giorgio; Barzon, Luisa
Title		Human cytomegalovirus productively infects adrenocortical cells and induces an early cortisol response
Type		članek
Source		J Cell Physiol
Vol. and No.		Letnik 221, št. 3
Publication year		2009
Volume		str. 629-41
Language		eng
Abstract		Following our recent findings on the presence of human cytomegalovirus (HCMV) in the normal human adrenal cortex and in adrenocortical tumors, especially in cortisol-secreting tumors, aim of the present study was to investigate the direct effects of HCMV infection on human adrenocortical cells. To this aim, both clinical isolates and laboratory strains of HCMV were used to assess the early effects of infection on human adrenocortical cell morphology, proliferation, gene expression, and steroidogenic function. Both clinical and laboratory HCMV strains could infect and replicate in primary human adrenocortical cell cultures and in adrenocortical carcinoma cell lines, leading to cytopathic changes. Most importantly, in the first hours post-infection (p.i.), adrenocortical cells showed a significant increase of cortisol and estrogen production, paralleled by up-regulation of steroidogenic acute regulatory protein and expression of steroidogenic enzymes involved in the last steps of adrenal steroidogenesis. This effect was probably due to HCMV immediate-early gene expression, since it was most evident in the early phases p.i. and UV-inactivated viral particles did not affect hormone production. Moreover, the effect on steroidogenesis was HCMV specific, since it was not observed after infection with herpes simplex virus. These data suggest that human adrenocortical cells are permissive to HCMV infection and acutely respond to infection with increased cortisol production. An acute glucocorticoid response is typically triggered by infections and is considered to be critical to host defense against pathogens, although, in the case of HCMV infection, it might also enhance viral replication and reactivation from latency.
Descriptors		CYTOMEGALOVIRUS INFECTIONS CYTOMEGALOVIRUS ADRENAL CORTEX DISEASES HYDROCORTISONE OLIGONUCLEOTIDE PROBES AMINOGLUTETHIMIDE CELL LINE CELL SURVIVAL CYTOPATHOGENIC EFFECT, VIRAL ESTRADIOL FIBROBLASTS GENE EXPRESSION HERPESVIRUS 1, HUMAN VIRUS REPLICATION KINETICS PHOSPHOPROTEINS TUMOR CELLS, CULTURED VIRAL ENVELOPE PROTEINS VIRAL MATRIX PROTEINS VIRAL PROTEINS APOPTOSIS