Báo cáo sinh học: Synergistic inhibition of human cytomegalovirus replication by interferon-alpha/beta and interferon-gamma

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành hóa học dành cho các bạn yêu hóa học tham khảo đề tài: Synergistic inhibition of human cytomegalovirus replication by interferon-alpha/beta and interferon-gamma
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Báo cáo sinh học: " Synergistic inhibition of human cytomegalovirus replication by interferon-alpha/beta and interferon-gamma"Virology Journal BioMed Central Open AccessResearchSynergistic inhibition of human cytomegalovirus replication byinterferon-alpha/beta and interferon-gammaBruno Sainz Jr†, Heather L LaMarca†, Robert F Garry and Cindy A Morris*Address: Department of Microbiology and Immunology, Program in Molecular Pathogenesis and Immunity, Tulane University Health SciencesCenter, 1430 Tulane Avenue, SL-38, New Orleans, LA, 70112, USAEmail: Bruno Sainz - bsainz@scripps.edu; Heather L LaMarca - hlamarc@tulane.edu; Robert F Garry - rfgarry@tulane.edu;Cindy A Morris* - cmorris2@tulane.edu* Corresponding author †Equal contributorsPublished: 23 February 2005 Received: 17 February 2005 Accepted: 23 February 2005Virology Journal 2005, 2:14 doi:10.1186/1743-422X-2-14This article is available from: http://www.virologyj.com/content/2/1/14© 2005 Sainz et al; licensee BioMed Central Ltd.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: Recent studies have shown that gamma interferon (IFN-γ) synergizes with the innate IFNs (IFN-α and IFN-β) to inhibit herpes simplex virus type 1 (HSV-1) replication in vitro. To determine whether this phenomenon is shared by other herpesviruses, we investigated the effects of IFNs on human cytomegalovirus (HCMV) replication. Results: We have found that as with HSV-1, IFN-γ synergizes with the innate IFNs (IFN-α/β) to potently inhibit HCMV replication in vitro. While pre-treatment of human foreskin fibroblasts (HFFs) with IFN-α, IFN-β or IFN-γ alone inhibited HCMV plaque formation by ~30 to 40-fold, treatment with IFN-α and IFN-γ or IFN-β and IFN-γ inhibited HCMV plaque formation by 163- and 662-fold, respectively. The generation of isobole plots verified that the observed inhibition of HCMV plaque formation and replication in HFFs by IFN-α/β and IFN-γ was a synergistic interaction. Additionally, real-time PCR analyses of the HCMV immediate early (IE) genes (IE1 and IE2) revealed that IE mRNA expression was profoundly decreased in cells stimulated with IFN-α/β and IFN-γ (~5-11-fold) as compared to vehicle-treated cells. Furthermore, decreased IE mRNA expression was accompanied by a decrease in IE protein expression, as demonstrated by western blotting and immunofluorescence. Conclusion: These findings suggest that IFN-α/β and IFN-γ synergistically inhibit HCMV replication through a mechanism that may involve the regulation of IE gene expression. We hypothesize that IFN-γ produced by activated cells of the adaptive immune response may potentially synergize with endogenous type I IFNs to inhibit HCMV dissemination in vivo. viral immediate early (IE), early and late genes occurs in aBackgroundHuman cytomegalovirus (HCMV) is a ubiquitous beta- stepwise fashion [2]. While generally asymptomatic inherpesvirus that affects 60–80% of the human population immunocompetent individuals, primary HCMV infection[1]. The lytic replication cycle of HCMV is a temporally may cause infectious mononucleosis and has been associ-regulated cascade of events that is initiated when the virus ated with atherosclerosis and coronary restenosis [3,4].binds to host cell receptors. Upon entry into the cell, the Furthermore, HCMV is the leading contributor of congen-viral DNA translocates to the nucleus, where expression of ital viral infections in the United States and Europe, Page 1 of 13 (page number not for citation purposes)Virol ...