Involvement of proteases in porcine reproductive and respiratory syndrome virus uncoating upon internalization in primary macrophages

Misinzo, Gerald; Delputte, Peter; Nauwynck, Hans

doi:10.1051/vetres:2008031

Cited by 22 publications

(15 citation statements)

References 45 publications

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“…Upon a pH drop, PRRSV is uncoated and its genome is released from the endosomes into the cytoplasm, which allows virus replication 22. After HP-PRRSV infection the ATP6V1B2 gene, which encodes a component of vacuolar ATPase (V-ATPase) that mediates acidification of endosomal organelles 23, was upregulated (Figure 3).…”

Section: Resultsmentioning

confidence: 99%

Molecular Characterization of Transcriptome-wide Interactions between Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus and Porcine Alveolar Macrophages in vivo

Zhou¹,

Zhai²,

Zhou³

et al. 2011

Int. J. Biol. Sci.

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Porcine reproductive and respiratory syndrome virus (PRRSV) infects mainly the porcine alveolar macrophages (PAMs) and causes porcine reproductive and respiratory syndrome (PRRS). Previous studies have analyzed the global gene expression profiles of lung tissue in vivo and PAMs in vitro following infection with PRRSV, however, transcriptome-wide understanding of the interaction between highly pathogenic PRRSV (HP-PRRSV) and PAMs in vivo has not yet been established. In this study, we employed Affymetrix microarrays to investigate the gene expression patterns of PAMs isolated from Tongcheng piglets (a Chinese indigenous breed) after infection with HP-PRRSV. During the infection, Tongcheng piglets exhibited typical clinical signs, e.g. fever, asthma, coughing, anorexia, lethargy and convulsion, but displayed mild regional lung damage at 5 and 7 dpi. Microarray analysis revealed that HP-PRRSV infection has affected PAMs in expression of the important genes involved in cytoskeleton and exocytosis organization, protein degradation and folding, intracellular calcium and zinc homeostasis. Several potential antiviral strategies might be employed in PAMs, including upregulating IFN-induced genes and increasing intracellular zinc ion concentration. And inhibition of the complement system likely attenuated the lung damage during HP-PRRSV infection. Transcriptomic analysis of PAMs in vivo could lead to a better understanding of the HP-PRRSV-host interaction, and to the identification of novel antiviral therapies and genetic components of swine tolerance/susceptibility to HP-PRRS.

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Section: Resultsmentioning

confidence: 99%

Molecular Characterization of Transcriptome-wide Interactions between Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus and Porcine Alveolar Macrophages in vivo

Zhou¹,

Zhai²,

Zhou³

et al. 2011

Int. J. Biol. Sci.

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“…In addition, successful infection is dependent on proteases that reside in the endosome, including cathepsin E and a yet unidentified serine protease (Misinzo et al, 2008). The role of the proteases is most likely to cleave and release the fusion peptide from the envelope proteins in order to initiate membrane fusion (Harrison, 2008).…”

Section: Virus Entrymentioning

confidence: 99%

The structural biology of PRRSV

2010

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Porcine reproductive and respiratory syndrome virus (PRRSV) is an enveloped, positive-sense single-stranded RNA virus belonging to the Arteriviridae family. Arteriviruses and coronaviruses are grouped together in the order Nidovirales, based on similarities in genome organization and expression strategy. Over the past decade, crystal structures of several viral proteins, electron microscopic studies of the virion, as well as biochemical and in vivo studies on protein-protein interactions have led to a greatly increased understanding of PRRSV structural biology. At this point, crystal structures are available for the viral proteases NSP1α, NSP1β and NSP4 and the nucleocapsid protein, N. The NSP1α and NSP1β structures have revealed additional non-protease domains that may be involved in modulation of host functions. The N protein forms a dimer with a novel fold so far only seen in PRRSV and other nidoviruses. Cryo-electron tomographic studies have shown the three-dimensional organization of the PRRSV virion and suggest that the viral nucleocapsid has an asymmetric, linear arrangement, rather than the isometric core previously described. Together, these studies have revealed a closer structural relationship between arteri- and coronaviruses than previously anticipated.

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“…The scavenger receptor CD163 has been shown to be essential for virus uncoating [40],[41]. A pH drop within the endosome is required [37],[42] and also the aspartic protease cathepsin E and a yet unidentified trypsin-like serine protease [43] have been implicated in this process.…”

Section: Introductionmentioning

confidence: 99%

The M/GP5 Glycoprotein Complex of Porcine Reproductive and Respiratory Syndrome Virus Binds the Sialoadhesin Receptor in a Sialic Acid-Dependent Manner

et al. 2010

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The porcine reproductive and respiratory syndrome virus (PRRSV) is a major threat to swine health worldwide and is considered the most significant viral disease in the swine industry today. In past years, studies on the entry of the virus into its host cell have led to the identification of a number of essential virus receptors and entry mediators. However, viral counterparts for these molecules have remained elusive and this has made rational development of new generation vaccines impossible. The main objective of this study was to identify the viral counterparts for sialoadhesin, a crucial PRRSV receptor on macrophages. For this purpose, a soluble form of sialoadhesin was constructed and validated. The soluble sialoadhesin could bind PRRSV in a sialic acid-dependent manner and could neutralize PRRSV infection of macrophages, thereby confirming the role of sialoadhesin as an essential PRRSV receptor on macrophages. Although sialic acids are present on the GP3, GP4 and GP5 envelope glycoproteins, only the M/GP5 glycoprotein complex of PRRSV was identified as a ligand for sialoadhesin. The interaction was found to be dependent on the sialic acid binding capacity of sialoadhesin and on the presence of sialic acids on GP5. These findings not only contribute to a better understanding of PRRSV biology, but the knowledge and tools generated in this study also hold the key to the development of a new generation of PRRSV vaccines.

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Involvement of proteases in porcine reproductive and respiratory syndrome virus uncoating upon internalization in primary macrophages

Cited by 22 publications

References 45 publications

Molecular Characterization of Transcriptome-wide Interactions between Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus and Porcine Alveolar Macrophages in vivo

Molecular Characterization of Transcriptome-wide Interactions between Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus and Porcine Alveolar Macrophages in vivo

The structural biology of PRRSV

The M/GP5 Glycoprotein Complex of Porcine Reproductive and Respiratory Syndrome Virus Binds the Sialoadhesin Receptor in a Sialic Acid-Dependent Manner

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