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Review
. 2012 Sep;4(9):1569-91.
doi: 10.3390/v4091569. Epub 2012 Sep 13.

Host cell factors as antiviral targets in arenavirus infection

Florencia N Linero  1 , Claudia S Sepúlveda, Federico Giovannoni, Viviana Castilla, Cybele C García, Luis A Scolaro, Elsa B Damonte
Affiliations
Review

Host cell factors as antiviral targets in arenavirus infection

Florencia N Linero et al. Viruses. 2012 Sep.

Abstract

Among the members of the Arenaviridae family, Lassa virus and Junin virus generate periodic annual outbreaks of severe human hemorrhagic fever (HF) in endemic areas of West Africa and Argentina, respectively. Given the human health threat that arenaviruses represent and the lack of a specific and safe chemotherapy, the search for effective antiviral compounds is a continuous demanding effort. Since diverse host cell pathways and enzymes are used by RNA viruses to fulfill their replicative cycle, the targeting of a host process has turned an attractive antiviral approach in the last years for many unrelated virus types. This strategy has the additional benefit to reduce the serious challenge for therapy of RNA viruses to escape from drug effects through selection of resistant variants triggered by their high mutation rate. This article focuses on novel strategies to identify inhibitors for arenavirus therapy, analyzing the potential for antiviral developments of diverse host factors essential for virus infection.

Keywords: Junin virus; antiviral; arenavirus; hemorrhagic fever; host cell target.

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Figures

Figure 1
Figure 1
Main host factors involved in arenavirus multiplication analyzed as potential antiviral targets. In an infected cell the cellular factors discussed in this article (IMPDH: inosine monophosphate dehydrogenase; CTPS: cytosine triphosphate synthetase; SAHH: S-adenosylhomocysteine hydrolase; OMPD: orotidylic acid decarboxylase; hnRNPs: heterogeneous nuclear ribonucleoproteins; PI3K/Akt: phosphatidylinositol-3-kinase/protein kinase B; MEK/ERK:mitogen-activated protein kinase/extracellular signal-regulated kinase; IRF-3: interferon regulatory factor 3; IKKε: inhibitor of nuclear factor kB kinase–related kinase; NF-κB: nuclear factor kappa B; RIG-I: retinoic acid-inducible gene I protein; PKR: protein kinase R; PML: promyelocytic leukemia protein; DG: dystroglycan; TfR: transferrin receptor) are indicated in red; other factors not discussed here (TSG101: tumor supresor gene 101; NMT: N-myristoyltransferase; SKI-1/S1P: subtilisin kexin isozyme-1/site 1 proprotein convertase; ATF-2: activating transcription factor 2; CREB: cAMP response element-binding [30,31,32,33] are in blue.
Figure 2
Figure 2
(a) Effect of PML on infectious particle production. Control-siRNAs, PML-siRNAs and pcDNA-PML transfected A549 cells were infected with an attenuated strain of JUNV. At 24 h post infection (p.i.) viral yields were determined by a standard plaque assay; (b) Determination of PML-mRNA expression levels. JUNV infected A549 cells were harvested at 24 h p.i. for qRT-PCR. PML-mRNA expression was represented as fold difference relative to mock infected cells and normalized to β-actin-mRNA; (c) Effect of JUNV infection on PML-NBs distribution. JUNV infected A549 cells were fixed 24 h p.i. and a double immunofluorescence was performed using monoclonal anti-nucleoprotein antibody visualized by fluorescein isothiocyanate and monoclonal anti-PML antibody visualized by tetramethyl rhodamine isothiocyanate. Cell nuclei were stained with 4',6-diamidino-2-phenylindole (DAPI) (400X).
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