Major receptor group common cold virus HRV89 was adapted to grow in HEp-2 cells, which are permissive for minor group human rhinoviruses (HRVs) but which only marginally support growth of major-group viruses. After 32 blind passages in these cells, each alternating with boosts of the recovered virus in HeLa cells, HRV89 acquired the capacity to effectively replicate in HEp-2 cells, attaining virus titers comparable to those in HeLa cells although no cytopathic effect was observed. Several clones were isolated and shown to replicate in HeLa cells whose ICAM-1 was blocked with monoclonal antibody R6.5 and in COS-7 cells, which are devoid of ICAM-1. Blocking experiments with recombinant very-low-density lipoprotein receptor fragments and enzyme-linked immunosorbent assays indicated that the mutants bound a receptor different from that used by minor-group viruses. Determination of the genomic RNA sequence encoding the capsid protein region revealed no changes in amino acid residues at positions equivalent to those involved in the interaction of HRV14 or HRV16 with ICAM-1. One mutation was within the footprint of a very-low-density lipoprotein receptor fragment bound to minor-group virus HRV2. Since ICAM-1 not only functions as a vehicle for cell entry but has also a "catalytic" function in uncoating, the use of other receptors must have important consequences for the entry pathway and demonstrates the plasticity of these viruses.Human rhinoviruses (HRVs), a major cause of mild upper respiratory infections generally recognized as common colds, are small icosahedral particles with a capsid composed of four viral proteins, VP1 through VP4 (for a review see reference 9). The capsid encases a genomic RNA of about 7,500 nucleotides encoding a polyprotein which is cotranslationally and autocatalytically processed by three viral proteinases, P2A, P3C, and P3CD (the precursor of P3C). A final maturation cleavage of VP0 to VP2 and VP4 occurs concomitantly with encapsidation by an as yet unidentified protease. With one exception (HRV87), the serotypes can be divided into a major group, using intercellular adhesion molecule 1 (ICAM-1) as the viral receptor, and a minor group, attaching to the cell via members of the low-density lipoprotein receptor (LDLR) family including LDLR, the very-low-density lipoprotein receptor (VLDLR), and LDLR-related protein (LRP) (16,27). The nature of the HRV87 receptor is unknown (50). Whereas major-group viruses are highly specific for human ICAM-1 and fail to attach to the homologue of other species, minor-group viruses bind to a variety of LDLRs, most likely due to the high evolutionary conservation of these membrane proteins. Replication usually does not occur in nonhuman cells even when suitable receptors are present, and adaptation of HRV2 to growth in mouse cells has been shown to be correlated with mutations in nonstructural proteins P2B and P2C (23).As HRVs of both receptor groups are very similar with respect to the amino acid sequence and the three-dimensional structure of the viral cap...
Human rhinoviruses (HRV) of the minor receptor group use several members of the low-density lipoprotein receptor superfamily for cell entry. These proteins are evolutionarily highly conserved throughout species and are almost ubiquitously expressed. Their common building blocks, cysteine-rich ligand binding repeats about 40 amino acids in length, exhibit considerable sequence similarity. Various numbers of these repeats are present in the different receptors. We here demonstrate that HRV type 1A (HRV1A) replicates in mouse cells without adaptation. Furthermore, although closely related to HRV2, it fails to bind to the human low-density lipoprotein receptor but recognizes the murine protein, whereas HRV2 binds equally well to both homologues. This difference went unnoticed due to the presence of other receptors, such as the low-density lipoprotein receptor-related protein, which allow species-independent attachment. The species specificity of HRV1A reported here will aid in defining amino acid residues establishing the contact between the viral surface and the receptor.Human rhinoviruses (HRVs) constitute a large genus within the family Picornaviridae and are the major cause of common cold infections (for a review on picornaviruses, see reference 43). Their icosahedral capsid is composed of 60 copies each of the viral proteins VP1, VP2, VP3, and VP4. The protein shell encases an RNA genome of positive polarity which is translated into a polyprotein upon arrival in the cytoplasm. The precursor protein is cleaved autocatalytically and cotranslationally by virally encoded proteases, giving rise to the capsid proteins and to the nonstructural proteins involved in replicative functions.Apart from one exception (HRV type 87 [HRV87]), the 102 serotypes are divided into a major and a minor group based on specific interaction with their cellular receptors, intercellular adhesion molecule 1 (ICAM-1; the major group) and members of the low-density lipoprotein receptor (LDLR) family (the minor group). Amino acid sequence information for the entire capsid protein region is available for 11 different serotypes (http://www.iah.bbsrc.ac.uk/virus/picornaviridae /SequenceDatabase/Index.html), and the three-dimensional structures of three major-group and two minor-group serotypes have been solved at atomic resolution (21,38,42,49,54). Medium-resolution structures from complexes of the majorgroup viruses HRV14 and HRV16 with soluble ICAM-1 (22, 39) as well as of the minor-group virus HRV2 and a soluble fragment of the very-low-density lipoprotein receptor (VLDLR) (14) have been obtained by image reconstruction from cryoelectron microscopy data. Whereas ICAM-1 binds inside the canyon, a cleft encircling the fivefold axes of icosahedral symmetry, the HRV2 receptor complex revealed that the BC loop and the HI loop of VP1 were largely covered by two of the three repeats of the recombinant VLDLR fragment VLDLR 1-3 , encompassing ligand binding repeats 1 to 3 only (41).The LDLR family comprises the LDLR proper, VLDLR, LDLR-related protein...
Chest computed tomography scan was the most effective screening investigation, which should be routinely used whenever curative surgery of head and neck cancer is planned. Abdominal ultrasound and bone scintigraphy may sometimes be valuable before extensive surgical treatment of far advanced disease. In patients scheduled for primary radiotherapy, radiologic screening had hardly any consequence and should be confined to conventional x-ray of the chest.
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