The small envelope protein of porcine reproductive and respiratory syndrome virus possesses ion channel protein-like properties

Lee, Changhee; Yoo, Dongwan

doi:10.1016/j.virol.2006.07.013

Cited by 77 publications

(63 citation statements)

References 51 publications

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“…Because the response is polyclonal, individual Igs cannot be recovered for sequencing to test this assumption unless they can be transformed and cloned. Accepting this assumption, the elevated level of IgG with hydrophobic binding sites could contain specific Abs to a hydrophobic epitope of a T cell-independent (TI) Ag from the viral envelope (52) or the amphipathic helix of the M protein (53). These may have been overlooked because commercial and experimental ELISAs depend on hydrophilic glycoproteins or nucleocapsid proteins (see below) and because ELISAs are biased against hydrophobic Abs (54).…”

Section: Discussionmentioning

confidence: 99%

Porcine Reproductive and Respiratory Syndrome Virus Subverts Repertoire Development by Proliferation of Germline-Encoded B Cells of All Isotypes Bearing Hydrophobic Heavy Chain CDR3

Butler

Wertz

Weber

et al. 2008

The Journal of Immunology

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Isolator piglets infected with porcine reproductive and respiratory syndrome virus (PRRSV), which is related to the lactate dehydrogenase-elevating virus of mice, develop severe hypergammaglobulinemia, lymph node adenopathy, and autoimmune disease. Many of the polyclonally activated B cell clones bear hydrophobic H chain CDR3s (HCDR3s) and are disseminated to most lymphoid tissues. We show in this study that B cells with identical hydrophobic HCDR3s are expressed with all major isotypes in PRRSV-infected piglets (PIPs), explaining why PRRSV-induced hypergammaglobulinemia is seen in all major isotypes. Up to one-third of randomly selected VDJ clones from the respiratory tract of PIPs have hydrophobic HCDR3s exclusively bearing VDJ rearrangements with CDR1, CDR2, and nearly intact DH segments in germline configuration. These HCDR3s are long and DHA and DHB are exclusively used in reading frame 3. A minimal tripeptide motif containing three hydrophobic amino acids (Leu, Val, and Ile) or any two plus alanine is common to this hydrophobic patch. We propose that PRRSV infection causes generalized Ag-independent B cell activation and hypergammaglobulinemia with biased expansion of a subpopulation of the preimmune repertoire with hydrophobic binding sites that normally disappears during Ag-driven repertoire diversification. Elevated Ig levels in PIP cannot be explained as antiviral Abs; some Igs can account for autoantibodies to dsDNA and Golgi, whereas those with hydrophobic binding sites may account for the Ig aggregates seen in PIPs and lactate dehydrogenase-elevating virus-infected mice. This diversion from normal repertoire development may explain the delayed immune response to PRRSV.

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Section: Discussionmentioning

confidence: 99%

Porcine Reproductive and Respiratory Syndrome Virus Subverts Repertoire Development by Proliferation of Germline-Encoded B Cells of All Isotypes Bearing Hydrophobic Heavy Chain CDR3

Butler

Wertz

Weber

et al. 2008

The Journal of Immunology

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“…Simian vimentin and CD151 were postulated to have a role in PRRSV infection of MARC-145 cells (Kim et al, 2006;Shanmukhappa et al, 2007). Additionally, the small envelope protein E of PRRSV has been implicated in infection of MARC-145 cells where it may function as a viroporin that facilitates uncoating of the virus and release of the viral genome into the cytoplasm (Lee & Yoo, 2006). The role of these molecules in infection of macrophages has however not been established.…”

Section: Other Entry Mediatorsmentioning

confidence: 99%

“…The genome release for example is not that well understood. Although some cellular and viral factors have been implicated in this process (Lee & Yoo, 2006;Misinzo et al, 2008;Van Gorp et al, 2008), their precise functions and modes of action remain unknown. Further fundamental research is necessary to obtain a complete picture of the PRRSV entry process.…”

Section: Future Perspectivesmentioning

confidence: 99%

Porcine reproductive and respiratory syndrome virus entry into the porcine macrophage

Breedam

Delputte

Gorp

et al. 2010

Journal of General Virology

179

119

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Porcine reproductive and respiratory syndrome virus (PRRSV) emerged in the late 1980s and rapidly became one of the most significant viral pathogens in the swine industry. In vivo, the virus shows a very narrow cell tropism and targets specific subsets of porcine macrophages. The entry of PRRSV into its host cell is the first crucial step in infection and has been the focus of many fundamental studies. This review provides a comprehensive overview of the current knowledge on PRRSV entry into the porcine macrophage, covering virus binding, internalization and genome release, and integrates these findings into a general model of the entry process. IntroductionPorcine reproductive and respiratory syndrome (PRRS) severely affects swine populations worldwide. The aetiological agent, the PRRS virus (PRRSV), is an RNA virus that is classified within the family Arteriviridae, order Nidovirales (Cavanagh, 1997). PRRSV causes considerable production losses as infection with the virus can result in severe reproductive and respiratory disorders in pigs (Neumann et al., 2005). With the recent outbreaks of highly virulent variants of the virus in China (Li et al., 2007;Tian et al., 2007;Zhou et al., 2008), interest in PRRSV has increased greatly and the demand for safe and effective vaccines for PRRSV control is higher than ever.The PRRSV virion consists of a nucleocapsid, composed of a positive-strand RNA genome (±15 kb) and the nucleocapsid protein (N), which is surrounded by a lipid bilayer envelope Dea et al., 1995;Mardassi et al., 1994;Meulenberg et al., 1993;Spilman et al., 2009;Wensvoort et al., 1992). The viral envelope contains six structural proteins: the small envelope protein E, the membrane protein M and the N-glycosylated glycoproteins GP 2 (or GP 2a ), GP 3 , GP 4 and GP 5 . M, N and GP 5 are the major structural proteins of PRRSV, while E, GP 2 , GP 3 and GP 4 are minor virion components. The M and GP 5 proteins occur as disulfide-linked heterodimers in the envelope, while the minor structural proteins E, GP 2 , GP 3 and GP 4 appear to associate via non-covalent interactions (Mardassi et al., 1995(Mardassi et al., , 1996Meulenberg et al., 1993Meulenberg et al., , 1995van Nieuwstadt et al., 1996; Wissink et al., 2005;Wu et al., 2001). In addition, recent data suggest that interactions exist between major and minor envelope proteins (Das et al., 2010).Since the discovery of PRRSV, many studies have been performed to gain insight into the biology of this important pathogen. This review reflects on two decades of research on the initial steps of the PRRSV replication cycle, covering virus attachment, internalization and disassembly. A general model of PRRSV entry into the porcine macrophage is proposed and delineates where further research is necessary. PRRSV cell tropismLike other members of the family Arteriviridae, PRRSV has a very narrow cell tropism. In vivo, the virus shows a preference for cells of the monocyte/macrophage lineage and infects specific subsets of differentiated macrophages in lungs, lymphoid ...

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“…ORF 2a= is absent in all nonsimian arterivirus genomes, and the function of the protein it encodes is unknown. ORF 2a encodes the E protein, which likely functions as an ion channel incorporated into the virion that may be important for host cell entry (26). Interactions among the "minor" (GP2, -3, and -4) arterivirus surface glycoproteins and E protein were reported as being important for arterivirion assembly (23,24).…”

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confidence: 99%

Within-Host Evolution of Simian Arteriviruses in Crab-Eating Macaques

Moncla

Weiler²,

Barry³

et al. 2017

J Virol

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Simian arteriviruses are a diverse clade of viruses infecting captive and wild nonhuman primates. We recently reported that Kibale red colobus virus 1 (KRCV-1) causes a mild and self-limiting disease in experimentally infected crabeating macaques, while simian hemorrhagic fever virus (SHFV) causes lethal viral hemorrhagic fever. Here we characterize how these viruses evolved during replication in cell culture and in experimentally infected macaques. During passage in cell culture, 68 substitutions that were localized in open reading frames (ORFs) likely associated with host cell entry and exit became fixed in the KRCV-1 genome. However, we did not detect any strong signatures of selection during replication in macaques. We uncovered patterns of evolution that were distinct from those observed in surveys of wild red colobus monkeys, suggesting that these species may exert different adaptive challenges for KRCV-1. During SHFV infection, we detected signatures of selection on ORF 5a and on a small subset of sites in the genome. Overall, our data suggest that patterns of evolution differ markedly among simian arteriviruses and among host species.IMPORTANCE Certain RNA viruses can cross species barriers and cause disease in new hosts. Simian arteriviruses are a diverse group of related viruses that infect captive and wild nonhuman primates, with associated disease severity ranging from apparently asymptomatic infections to severe, viral hemorrhagic fevers. We infected nonhuman primate cell cultures and then crab-eating macaques with either simian hemorrhagic fever virus (SHFV) or Kibale red colobus virus 1 (KRCV-1) and assessed within-host viral evolution. We found that KRCV-1 quickly acquired a large number of substitutions in its genome during replication in cell culture but that evolution in macaques was limited. In contrast, we detected selection focused on SHFV ORFs 5a and 5, which encode putative membrane proteins. These patterns suggest that in addition to diverse pathogenic phenotypes, these viruses may also exhibit distinct patterns of within-host evolution both in vitro and in vivo.KEYWORDS evolution, simian arterivirus, simian hemorrhagic fever virus, virology, within-host diversity I n 1964, acute outbreaks of a highly lethal viral hemorrhagic fever caused by a previously unknown agent swept through captive nonhuman primate research facilities in the former Soviet Union and the United States (1-4). Although the origin and

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The small envelope protein of porcine reproductive and respiratory syndrome virus possesses ion channel protein-like properties

Cited by 77 publications

References 51 publications

Porcine Reproductive and Respiratory Syndrome Virus Subverts Repertoire Development by Proliferation of Germline-Encoded B Cells of All Isotypes Bearing Hydrophobic Heavy Chain CDR3

Porcine Reproductive and Respiratory Syndrome Virus Subverts Repertoire Development by Proliferation of Germline-Encoded B Cells of All Isotypes Bearing Hydrophobic Heavy Chain CDR3

Porcine reproductive and respiratory syndrome virus entry into the porcine macrophage

Within-Host Evolution of Simian Arteriviruses in Crab-Eating Macaques

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