Mechanistic antiviral studies on hemorrhagic fever viruses using global gene expression profiles

C. GARCÍA; C. SEPÚLVEDA; K. MARTIN; E. DAMONTE; I. BOSCH

Brujas, Bélgica

Congreso; XIV Negative Strand Virus Meeting; 2010

<!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman";} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> Several members of Arenaviruses such as Junín virus (JUNV) and Lassa virus cause hemorrhagic fevers in human beings. The virions contain bisegmented single-stranded RNA genomes that have ambisense coding strategy and express five different products: a nucleocapsid protein, an envelope glycoprotein precursor that is processed into GP1 and GP2, an RNA polymerase and the matrix protein called Z. In previous studies we have shown that disulfides compounds have antiviral and virucidal properties against arenaviruses. The present study was focused on the modulation of gene expression in a human hepatic cell lineage, HepG2, in response to Junín Virus infection and the treatment with disulfide antiviral compounds characterized in our laboratory. Using microarray data analysis, we investigated the global gene expression changes in HepG2-JUNV infected cells, after 24 and 48 h in the presence or absence of the disulfide compounds. The results showed that JUNV infection leads to alterations in numerous genes that constitute important signaling pathways in HepG2 cells. Among them, genes related to the innate immune response pathways and metallothioneins raised particular interest. To better explore their role during the course of JUNV infection, the expression pattern of several cellular antiviral genes were validated through real-time PCR technique. The results presented here comprise part of the initial steps to guide the efforts toward the elucidation of the mechanisms triggered by disulfide compounds to block JUNV infection in liver cells.