A putative receptor for Venezuelan equine encephalitis virus from mosquito cells

Ludwig, George V.; Kondig, John P.; Smith, Jonathan

doi:10.1128/jvi.70.8.5592-5599.1996

Cited by 115 publications

(47 citation statements)

References 39 publications

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“…Sindbis virus uses LamR as a functional receptor to enter BHK-21 cells (39). Mosquito LamR was found to be a putative receptor for Venezuelan equine encephalitis virus (40) and dengue virus (41)(42)(43)(44). In mammalian cells, LamR acts as a cellular receptor for the cellular prion protein (PrP) (45,46), and it mediates the infection of adeno-associated virus serotypes 8, 2, 3, and 9 (47).…”

Section: Discussionmentioning

confidence: 99%

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The Laminin Receptor Is a Cellular Attachment Receptor for Classical Swine Fever Virus

Chen

Shen

et al. 2015

J Virol

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Classical swine fever virus (CSFV) is the causative agent of classical swine fever (CSF), a highly contagious, economically important viral disease in many countries. The E rns and E2 envelope glycoproteins are responsible for the binding to and entry into the host cell by CSFV. To date, only one cellular receptor, heparan sulfate (HS), has been identified as being involved in CSFV attachment. HS is also present on the surface of various cells that are nonpermissive to CSFV. Hence, there must be another receptor(s) that has been unidentified to date. In this study, we used a set of small interfering RNAs (siRNAs) against a number of porcine cell membrane protein genes to screen cellular proteins involved in CSFV infection. This approach resulted in the identification of several proteins, and of these, the laminin receptor (LamR) has been demonstrated to be a cellular receptor for several viruses. Confocal analysis showed that LamR is colocalized with CSFV virions on the membrane, and a coimmunoprecipitation assay indicated that LamR interacts with the CSFV E rns protein. In inhibition assays, anti-LamR antibodies, soluble laminin, or LamR protein significantly inhibited CSFV infection in a dose-dependent manner. Transduction of PK-15 cells with a recombinant lentivirus expressing LamR yielded higher viral titers. Moreover, an attachment assay demonstrated that LamR functions during virus attachment. We also demonstrate that LamR acts as an alternative attachment receptor, especially in SK6 cells. These results indicate that LamR is a cellular attachment receptor for CSFV. IMPORTANCE Classical swine fever virus (CSFV) is the causative agent of classical swine fever (CSF), an economically important viral disease affecting the pig industry in many countries. To date, only heparan sulfate (HS) has been identified to be an attachment receptor for CSFV. Here, using RNA interference screening with small interfering RNAs (siRNAs) against a number of porcine membrane protein genes, we identified the laminin receptor (LamR) to be another attachment receptor. We demonstrate the involvement of LamR together with HS in virus attachment, and we elucidate the relationship between LamR and HS. LamR also serves as an attachment receptor for many viral pathogens, including dengue virus, a fatal human flavivirus. The study will help to enhance our understanding of the life cycle of flaviviruses and the development of antiviral strategies for flaviviruses. C lassical swine fever virus (CSFV) is the causative agent of classical swine fever (CSF), a highly contagious and often fatal viral disease in pigs. The disease leads to significant economic losses in many countries. CSFV is a member of the Pestivirus genus within the Flaviviridae family (1). The virus possesses a singlestranded, positive-sense RNA genome of approximately 12.3 kb (2, 3). Its genome contains a single, large open reading frame that encodes a precursor polyprotein of 3,898 amino acids (aa). The polyprotein is co-and posttranslationally processed by viral an...

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Section: Discussionmentioning

confidence: 99%

“…These membrane proteins were low-density lipoprotein receptor (LDLr), LamR, and vinculin. Among these, LamR has been identified to be a cellular receptor for different pathogens (38)(39)(40)(41)(42)(43)(44)(45)(46)(47). As shown in Fig.…”

Section: Membrane Proteins Required For Csfv Infection Were Screened mentioning

confidence: 99%

The Laminin Receptor Is a Cellular Attachment Receptor for Classical Swine Fever Virus

Chen

Shen

et al. 2015

J Virol

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“…LRP has been found on 40S ribosomes and was dubbed p40 (Auth and Brawerman, 1992), in the nucleus (Sato et al ., 1996) and on the cell surface. The 37‐kDa LRP is located in plasma membrane fractions of mosquito cells acting as a receptor for the Venezuelan equine encephalitis virus (Ludwig et al ., 1996), in cell‐wall fractions of Candida albicans (Lopez‐Ribot et al ., 1994) and on the cell surface of mammalian cells such as Madin–Darby canine kidney cells (Salas et al ., 1992). We showed by IF, flow cytometry and analysis of plasma membrane fractions that the 37‐kDa LRP is located on the surface of neuroblastoma cells and non‐transfected or LRP::FLAG hyperexpressing BHK cells.…”

Section: Discussionmentioning

confidence: 99%

The 37-kDa/67-kDa laminin receptor acts as the cell-surface receptor for the cellular prion protein

2001

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“…DEN-1 Ligand Blot. Ligand blot analysis was performed as a viral overlay binding assay, as described previously, 33 with minor modifications. Approximately 100 g HuH-7 membrane proteins were resolved on a 10% SDS-PAGE and blotted to a nitrocellulose membrane using a semidry transfer apparatus (BioRad, Hercules, CA).…”

Section: Methodsmentioning

confidence: 99%

Heparan Sulfate Proteoglycans Initiate Dengue Virus Infection of Hepatocytes

2000

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The clinical pictures caused by the arthropod-borne dengue viruses (DEN), which belong to the family of Flaviviridae, vary from a simple febrile fatigue to severe hemorrhagic fever and the often rapidly fatal dengue shock syndrome. 1 Consistent with a worldwide escalation of infection rates during the last decade, the more severe manifestations are occurring in an increasing proportion of cases. 2 Although DEN infections are a particular threat in tropical and subtropical regions, endemic transmission has recently returned to the continental United States. 3 The role of the liver in DEN infection has been generally underestimated, although the infection is regularly associated with elevated liver enzymes. More recent reports suggest the liver to be one of the ultimate target organs and hepatocytes a major site of viral replication in vivo. 4,5 In a frequent number of cases DEN infection causes acute hepatitis with liver failure and hepatic encephalopathy. 6-9 Aside from their own impact on liver cells, DEN provides a potential model for hepatitis C virus (HCV) infection, which at present cannot be grown in cell culture or small animal models.Although the initial steps of infection are a critical determinant of tissue tropism and therefore pathogenesis, little is known about the molecular basis of DEN-or of any other flavivirus-binding to their target cells, and the endocytic itineraries they follow. A growing list of structurally different viruses and certain other microbial agents have been previously shown to utilize sulfated glycosaminoglycans (GAG) such as heparan sulfates (HS) for initial binding to target cells. [10][11][12][13][14][15][16][17] HS is a repeating highly negative-charged linear copolymer of variably sulfated uronic acid and glucosamine carbohydrate residues. 18 Cell surface HS are attached to protein core molecules, some of which are transmembrane proteins with conserved cytoplasmic domains, capable of intracellular signaling. 19 These heparan sulfate proteoglycans (HSPG) provide the main GAG proportion of the cell surface. The presumed physiologic function of these molecules is the promotion of cellular adhesion to the extracellular matrix and the maintenance of boundaries between tissues of different types. 20 They are known to bind a large number of polypeptide growth factors and are involved in intracellular signaling in response to these molecules. 21 HSPG are ubiquitously distributed in the matrix and cell membrane of most tissues, but a distinct cell-and tissue-specific expression pattern 22 may contribute to differential targeting of viruses. They are not believed to be the sole mediator of viral uptake, although endosomal cycling of some HSPG subtypes have been described. 23 This led to the suggestion that infection of different viruses might be a two-or multi-step process, initial contact being with a low-affinity HSPG-receptor followed by transfer to the high-affinity receptor for internalization. 10,24,25 Internalization of flaviviruses is generally believed to be a receptor-med...

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A putative receptor for Venezuelan equine encephalitis virus from mosquito cells

Cited by 115 publications

References 39 publications

The Laminin Receptor Is a Cellular Attachment Receptor for Classical Swine Fever Virus

The Laminin Receptor Is a Cellular Attachment Receptor for Classical Swine Fever Virus

The 37-kDa/67-kDa laminin receptor acts as the cell-surface receptor for the cellular prion protein

Heparan Sulfate Proteoglycans Initiate Dengue Virus Infection of Hepatocytes

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