PubMed Health⌕ Search

Biomedical subjects

R Xu

Publications and source records attributed to R Xu.

At least 163 records · Page 9Linked to original sources
PubMed1998

A cell surface protein with herpesvirus entry activity (HveB) confers susceptibility to infection by mutants of herpes simplex virus type 1, herpes simplex virus type 2, and pseudorabies virus.

Certain mutant strains of herpes simplex virus type 1 (HSV-1) are unable to infect cells in which entry is dependent on HVEM, the previously described herpesvirus entry mediator designated here as herpesvirus entry protein A (HveA). These mutant viruses can infect other cells where entry is apparently dependent on other co-receptors. The mutant virus HSV-1(KOS)Rid1 was used to screen a human cDNA expression library for ability of transfected plasmids to convert resistant Chinese hamster ovary cells to susceptibility to virus entry. A plasmid expressing the previously described poliovirus receptor-related protein 2 (Prr2) was isolated on the basis of this activity. This protein, designated here as HveB, was shown to mediate the entry of three mutant HSV-1 strains that cannot use HVEM as co-receptor, but not wild-type HSV-1 strains. HveB also mediated the entry of HSV-2 and pseudorabies virus but not bovine herpesvirus type 1. HveB was expressed in some human neuronal cell lines, fibroblastic cells, keratinocytes, and primary activated T lymphocytes. Antibodies specific for HveB blocked infection of HveB-expressing CHO cells and a human fibroblastic cell strain HEL299. Differences in ability of HSV-1 and HSV-2 strains to use HveB for entry should influence the types of cells that can be infected and thereby account in part for serotype and strain differences in tissue tropism and pathogenicity.

Alphaherpesvirinae↗
PubMed1998

Expression of the proto-oncogene Ret, a component of the GDNF receptor complex, persists in human substantia nigra neurons in Parkinson's disease.

The proto-oncogene Ret, a membrane-associated receptor protein tyrosine kinase, has recently been shown to be a component of the glial cell line-derived neurotrophic factor (GDNF) receptor complex. GDNF has potent dopaminergic neurotrophic properties and has been suggested as a treatment for Parkinson's disease (PD). In this study, tissue sections of human substantia nigra (SN) from normal and PD cases were examined to determine the pattern of Ret expression in this region, and whether there was continued Ret expression in surviving dopaminergic neurons in PD cases. Using a polyclonal antibody to the amino terminal of Ret, immunoreactivity was localized in the SN to dopaminergic neurons. The antibody predominantly identified punctate deposits within cells. A similar pattern of immunoreactivity was observed in rat and monkey SN neurons. In neurologically normal cases, immunoreactivity was detected in many of the SN neurons. In all the PD cases studied, continued expression of Ret was observed in many of the surviving dopaminergic neurons. In certain cases, it was also detected on cells with the morphology of microglia. Ret expression by microglia was confirmed by immunoblot analysis on the human THP-1 macrophage type cell line. However, these cells did not express the mRNA for GDNFRalpha, the other component of the GDNF receptor complex.

Adult↗
PubMed1998

Anatomic considerations of pedicle screw placement in the thoracic spine. Roy-Camille technique versus open-lamina technique.

STUDY DESIGN: In this cadaveric study, the outcomes of two techniques for pedicle screw placement in the thoracic spine were compared. OBJECTIVES: To assess the Roy-Camille technique, and to determine whether pedicle screw placement, aided by partial laminectomy, could decrease the incidence of pedicle violations. SUMMARY OF BACKGROUND DATA: Pedicle screw fixation in the thoracic spine remains technically challenging. The Roy-Camille method may be one of the leading techniques of thoracic pedicle screw placement. However, there are few studies evaluating this technique and determining methods to decrease the incidence of thoracic pedicle penetration with screw insertion. METHODS: Ten cadaveric thoracic spines from T1 to T10 were used for pedicle screw placement. Two techniques of transpedicular screw placement were used, the Roy-Camille technique (screw placed on the right side; used in 95 screw placements) and the open-lamina technique screw placement with combined partial laminectomy (screw placed on the left side; used in 94 screw placements). After screw placement, all specimens were evaluated visually to determine violation of the pedicle. RESULTS: The screw placement with the Roy-Camille technique had a higher percentage of pedicle violation (54.7%) than did that with the open-lamina technique (15.9%). No Grade III violation was seen in the screw placement with the open-lamina technique. CONCLUSIONS: The Roy-Camille technique was associated with a high incidence of pedicle violation, whereas screw placement with a partial laminectomy significantly reduced the incidence of pedicle violation. Pedicle screw fixation in the thoracic spine remains a technical challenge and should not be used routinely. Screw placement with the open-lamina technique is recommended if pedicle screw fixation is strongly indicated in the thoracic spine.

Aged↗
PubMed1998

Sequence dependence and characteristics of bends induced by site-specific polynuclear aromatic carcinogen-deoxyguanosine lesions in oligonucleotides.

The tumorigenic metabolite of benzo[a]pyrene, the (+)-7R,8S,9S,10R enantiomer, and the nontumorigenic mirror-image isomer, (-)-7S,8R,9R, 10S, of r7,t8-dihydroxy-t9,10-epoxy-7,8,9, 10-tetrahydrobenzo[a]pyrene (anti-BPDE) bind covalently to the exocyclic amino group of deoxyguanosine (N2-dG) in native DNA. These adducts can cause structural perturbations such as DNA bends, which in turn may influence the cellular processing of these lesions. The characteristics of bends in site-specifically modified oligodeoxyribonucleotide duplexes induced by single (+)- and (-)-anti-[BP]-N2-dG lesions were examined by self-ligation and gel electrophoresis techniques. The modified residues (dG*) were centrally positioned in the 11-mer oligonucleotide d(CACAXG*XACAC) complexed with the natural complementary strands, with X = T or C, or in oligonucleotides 16 or 22 base pairs long with the same centrally positioned 11-mer. Among the four stereochemically distinct lesions, the 10S(+)-trans-anti-[BP]-N2-dG adducts were significantly more bent than any of the other three stereoisomeric adducts and were selected for detailed studies. In the TG*T sequence context (X = T), the retardation factor RL (apparent length of multimer/sequence length) is approximately independent of the phasing (distance, in base pairs, between the lesions) of the adducts with respect to the helical repeat (10.5 base pairs/helix turn). In contrast, in the CG*C sequence context (X = C), RL is markedly lower in the case of ligated 16-mers than in the case of ligated 11-mer duplexes. The dependence of RL on the phasing of the bends as a function of the helical repeat, indicate that the bends associated with (+)-trans-anti-[BP]-N2-dG lesions are relatively rigid in the d(...CG*C...).d(...GCG...) sequences, and flexible in the d(...TG*T...).d(...ACA...) sequence context. These differences are attributed to the orientations of the pyrenyl residues on the 5'-side of the modified deoxyguanosine residues in the minor groove and to the intrinsic roll and tilt characteristics of DNA dinucleotide steps CG, GC, TG, and GT. The influence of flanking bases on the extent and character of DNA bending suggest that base sequence effects may be important in the cellular processing of (+)-trans-anti-[BP]-N2-dG lesions.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1998

Electrochemical oxidation of N-acyldopamines and regioselective reactions of their quinones with N-acetylcysteine and thiourea.

The metabolism of catechols often involves their oxidation to quinones and subsequent nucleophilic addition reactions with sulfur-containing compounds. Adducts formed during these reactions may play important roles in many biological systems. We have studied the electrochemical oxidation of N-acetyldopamine (NADA) and N-beta-alanyldopamine (NBAD) in the presence of two sulfur-centered nucleophiles, N-acetylcysteine (NACySH) and thiourea (TU), and have characterized the adducts and reaction pathways. NADA and NBAD react similarly, but their adducts with NACySH and TU were formed regioselectively. NACySH yields mainly 5-adducts and TU only 6-adducts. The NACySH adducts are oxidized more easily than the parent N-acyldopamine, and their oxidations are chemically reversible. However, the TU adducts are more difficult to oxidize, and their oxidation products undergo further chemical reactions. An intramolecular base catalysis mechanism for adduct formation with NACySH is proposed, which facilitates removal of the proton from the sulfhydryl group of NACySH and directs formation of the 5-adduct via a 1,6-Michael addition reaction. The absence of a proton on the thioureylene sulfur atom leads to formation of the 6-thioureylene adduct via a 1,4-Michael addition reaction of TU. This mechanism is consistent with the formation of other sulfur-centered adducts of catechols previously reported in the literature.

Acetylcysteine↗
PubMed1998

Assessment of lumbosacral fusion mass by angled radiography. Technical notes.

STUDY DESIGN: Lumbosacral fusion masses were assessed by angled radiography. OBJECTIVES: To introduce the use of the angled anteroposterior radiograph in the evaluation of the fusion mass at the lumbosacral region. SUMMARY OF BACKGROUND DATA: Determination of the presence and progress of the fusion mass at the lumbosacral junction may be difficult clinically and radiologically. Few studies regarding the use of the angled anteroposterior view of plain radiographs in evaluating L5-S1 fusion are available. METHODS: The patient was placed in the supine position, and an angled view of the lumbosacral junction was obtained. Radiography of the angled anteroposterior view was performed with the x-ray beam oriented toward the cranial portion at 50 degrees to 55 degrees relative to the x-ray table. RESULTS: The use of the angled view of the lumbosacral junction eliminates the superimposition of the L5 transverse process on the posterior part of the superior ala of the sacrum, widens the L5-S1 intertransverse space, and enhances direct visualization. CONCLUSIONS: The use of the angled anteroposterior view on plain radiographs is recommended in the evaluation of the fusion status at L5-S1.

Arthrography↗
PubMed1998

Lateral radiologic evaluation of lateral mass screw placement in the cervical spine.

STUDY DESIGN: Assessment of the value of lateral radiographs in evaluation of lateral mass screw placement in the cervical spine. OBJECTIVES: To assess the value of lateral radiographs in determining the safe or hazardous locations of the tips of screws used in lateral mass screw fixation. SUMMARY OF BACKGROUND DATA: Posterior plating with lateral mass screw fixation is frequently used to stabilize the cervical spine and improve fusion. Injury to the spinal nerves caused by screws that are too long must be identified quickly to minimize neurologic complication. No previous radiologic study in which lateral mass screw placement was evaluated using lateral radiographs has been reported. METHODS: Six cervical spines were removed from embalmed cadavers. Three screws using the Roy-Camille technique and another three using Magerl technique were placed into the lateral mass at C3-C5 in each specimen. Four screw placements under direct visualization, including placement of the screw tip staying the ventral cortex and 2-mm, 4-mm, and 6-mm overpenetration of the ventral cortex, were performed separately on each specimen for each of the two techniques. After each placement, a lateral radiograph was taken. Each vertebral body was divided vertically into four equal zones with Zone I the most posterior. Another equal zone, posterior to the posterior border of the vertebral body was defined as pre-Zone I. The number of screw tips seen in each zone were quantified for each placement. RESULTS: In the screws placed using the Roy-Camille technique, 77.8% of screws placed without perforating the ventral cortex were found in Zone I; 72.2% placed with 2-mm overpenetration of the ventral cortex were noted in Zone II; and 61.1% of the screws with 4-mm overpenetration of ventral cortex and 77.8% with 6-mm overpenetration were located in Zone III. For the use of the Magerl technique, 44.4% of the screws placed without perforating the ventral cortex were found in pre-Zone I; 72.2% of the screws placed with 2-mm overpenetration were located in Zone I; and 66.6% with 4-mm overpenetration and 89.7% with 6-mm overpenetration were noted in Zones I and II, respectively. CONCLUSIONS: Lateral radiographs may be valuable in evaluating lateral mass screw placement. Ideal screw tip positions on lateral radiograph for the Roy-Camille technique may be in Zone I, and for the Magerl technique may be in pre-Zone I.

Aged↗
PubMed1998

The quantitative anatomy of the vertebral artery groove of the atlas and its relation to the posterior atlantoaxial approach.

STUDY DESIGN: An evaluation of the vertebral artery groove of the atlas vertebra using dry bony vertebrae. OBJECTIVES: To measure the dimension of the vertebral artery groove of the atlas and to define its relation to the posterior midline. SUMMARY OF BACKGROUND DATA: Anatomic descriptions of the vertebral artery groove of the atlas exist, but very little quantitative data focused on this groove have been reported. METHODS: Fifty dry atlas vertebrae were obtained for this study. Anatomic evaluation focused on the vertebral artery groove and its relation to the midline. A total of eight linear and two angular measurements were made bilaterally. The mean, range, and standard deviation were calculated for all of the specimens and for male and female specimens separately. RESULTS: Differences in dimensions of male and female specimens were found to be statistically significant in one linear and two angular parameters. The average depths of the medial and lateral entrances, lengths of the axis, and thicknesses of the vertebral artery groove for male and female specimens were 9 mm, 6 mm, 14 mm, and 4 mm, respectively. The average angle of the vertebral artery groove axis for both genders was 64 degrees lateral to the sagittal plane. The distances from the midline to the medial-most edge of the vertebral artery groove on the inner and outer cortexes for male and female specimens averaged 10 mm, with a minimum of 8 mm, and 18 mm, with a minimum of 12 mm, respectively. CONCLUSIONS: The results of this study suggest that dissection on the posterior aspect of the posterior ring should remain within 12 mm lateral to the midline, and dissection on the superior aspect of the posterior ring should remain within 8 mm of the midline.

Adult↗
PubMed1998

Bending and circularization of site-specific and stereoisomeric carcinogen-DNA adducts.

The potent tumorigen and mutagen (+)-7(R),8(S)-dihydroxy-9(S), 10(R)-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene ((+)-anti-BPDE) is a metabolite of benzo[a]pyrene that binds predominantly to the exocyclic amino group of guanine residues in DNA in vivo and in vitro. While the (-)-7S,8R,9R,10Senantiomer, (-)-anti-BPDE, also reacts with DNA to form similar covalent N2-deoxyguanosyl adducts, this diol epoxide is nontumorigenic and its mutagenic activities are different from those of (+)-anti-BPDE. In this work, T4 ligase-induced cyclization methods have been employed to demonstrate that the (+)-anti-[BP]-N2-dG lesions (G*) cause significantly greater amounts of bending and circularization of the one-base overhang undecamer duplex 5'-d(CACAT[G*]TACAC).d(TGTACATGTGG) than the stereoisomeric oligonucleotide duplex with G* = (-)-anti-[BP]-N2-dG. In the case of the (+)-anti-BPDE-modified oligonucleotides, the ratio of circular to linear DNA multimers reaches values of 8-9 for circle contour sizes of 99-121 base pairs, while for the (-)-anti-[BP]-N2-dG-modified DNA this ratio reaches a maximum value of only approximately 1 at 154-176 base pairs. Assuming a planar circle DNA model, the inferred bending angles for 90-92% of the observed circular ligation products range from 30 to 51 degrees per (+)-trans-anti-[BP]-N2-dG lesion and from 20 to 40 degrees per (-)-trans-anti-[BP]-N2-dG lesion. In the case of unmodified DNA, the probability of circular product formation is at least 1 order of magnitude less efficient than in the BPDE-modified sequences and about 90% of the circular products exhibit bending angles in the range of 14 -19 degrees . In the most abundant circular products observed experimentally, the bending angles are 40 degrees and 26 +/- 2 degrees per (+)-anti-[BP]- or (-)-anti-[BP]-modified 11-mer; these values correspond to a net contribution of 21-26 degrees and 5-19 degrees , respectively, to the observed overall bending per lesion. The coexistence of circular DNA molecules of different sizes and, therefore, different average bending angles per lesion, suggest that the lesions induce both torsional flexibility and flexible bends, which permit efficient cyclization, especially in the case of (+)-trans-[BP]-N2-dG adducts. The NMR characteristics of (+)-trans-[BP]-N2-dG lesion in the 11-mer duplex 5'-d(CACAT[G*]TACAC).d(GTGTACATGTG) indicate that all base pairs are intact, except at the underlined base pairs. This suggests a distortion in the normal conformation of the duplex on the 5'-side of the modified guanosine residue, which may be due to bending enhanced base pair opening and bending induced by the bulky carcinogen residue. The implications of base sequence-dependent flexibilities and conformational mobilities of anti-[BP]-N2-dG lesions on DNA replication and mutation are discussed.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1998

Effect of dietary catechin and vitamin E on aortic fatty streak accumulation in hypercholesterolemic hamsters.

Male golden Syrian hamsters were fed for 16 weeks on a hypercholesterolemic diet containing, per kg, 150 g of lipids (90 g butterfat, 35 g vitamin E-stripped corn oil and 25 g fish oil), 2 g cholesterol and either 3 IU vitamin E (3 IU E), 3 IU vitamin E and 200 mg catechin hydrate (3 IU E-200 Cat) or 30 IU vitamin E (30 IU E). More fatty streaks, measured by Oil Red O staining, were deposited in aortas of hamsters fed 3 IU E than in those fed either 3 IU E-200 Cat or 30 IU E. Lipid staining increased with plasma low-density lipoprotein cholesterol (LDL-C) in all animals. At the same concentration of LDL-C, animals fed either 3 IU E-200 Cat or 30 IU E developed less fatty streaks than those fed 3 IU E. Plasma LDL-C and total cholesterol were highest in hamsters fed 3 IU E and LDL-C and total cholesterol in animals fed 3 IU-200 Cat were not different from those fed either 3 IU E or 30 IU E. This study showed the importance of circulating plasma LDL-C on atherogenesis and the inhibitory effect on this process of both dietary vitamin E and catechin.

Animals↗
PubMed1998

Antifungal alkaloids and limonoid derivatives from Dictamnus dasycarpus.

From the root bark of Dictamnus dasycarpus (Rutaceae), four limonoid derivatives, two furoquinoline alkaloids, five limonoids, two sesquiterpenes and three steroids were isolated and their structures elucidated on the basis of various spectroscopic methods. Among the identified compounds, one was determined to be a new natural product, 6 beta-hydroxyfraxinellone, while six compounds were found to be active against the plant pathogenic fungus Cladosporium cucumerinum. The relationship between the structures of limonoid derivatives and their inhibitory activity against fungal growth was investigated.

Alkaloids↗
PubMed1998

Cloning and characterization of the presenilin-2 gene promoter.

Mutations in the presenilin-2 (PS-2) have been shown to cause early onset Alzheimer's disease (AD) in a series of families known as the Volga Germans and in an unrelated Italian kindred. Expression of the PS-2 gene is regulated during AD, aging, development and brain injury. Although expressed primarily in neurons, enhanced levels of PS-2 have been reported in astrocytes activated by neuronal damage. Understanding the regulation of the PS-2 gene may thus provide an insight into its role in AD. We have isolated a 3635 bp DNA fragment that contains 2934 bp of DNA sequence upstream from the PS-2 gene. Primer extension analysis was used to map three major transcriptional start sites within the PS-2 gene. The promoter sequence, upstream of each transcriptional start site, does not contain TATA or CAAT boxes but does contain several GC rich sites (Sp-1 and AP-2). A reporter gene construct containing the PS-2 promoter (PS2P, -2934 to +702) transfected into M17 cells drives basal transcription to 20% of the levels of the SV-40 viral promoter. Addition of NGF to PC-12 cells was found to upregulate the PS2P promoter and an NGF-responsive element was localized by deletional analysis between -403 and +13 within the promoter. Since the PS-2 gene has multiple start sites and the upstream sequence is GC rich with no TATA box, the PS-2 promoter is consistent with the GC class of 'housekeeping' genes.

5' Untranslated Regions↗
PubMed1998

Separation of cis elements responsive to ethylene, fruit development, and ripening in the 5'-flanking region of the ripening-related E8 gene.

The E8 gene is expressed at a high level during fruit ripening, and is transcriptionally activated by ethylene. We have identified a 428 bp fragment of the E8 5'-flanking region, from -1528 to -1100, that makes a minimal 35S promoter responsive to ethylene. This fragment confers ethylene-responsiveness only in the 5'-to-3' orientation; in the reverse orientation it results in increased expression in unripe fruit. Interestingly, this ethylene-responsive construct does not have high levels of expression during fruit ripening, indicating that sequences required for high level expression during fruit ripening are separate from sequences required for ethylene response. The ethylene-responsive sequences of the E8 5'-flanking region interact with the same DNA-binding protein that interacts with sequences required for ethylene responsiveness of the coordinately regulated E4 gene. We also conducted experiments to test the function of a second DNA-binding protein that interacts with both E4 and E8 5'-flanking sequences, the E4/E8-binding protein (E4/E8BP). We examined the effect of an internal deletion from -1088 to -863, which includes the binding site for E4/E8BP, on gene expression. This deletion did not affect expression in ripening fruit, and did not impair ethylene responsiveness. The deletion had a negative effect on expression in unripe fruit, but resulted in increased expression in leaves. These results suggest that the E4/E8BP is not critical for high levels of expression during fruit ripening or for ethylene response, but may play a role in organ-specific gene transcription.

Binding Sites↗
PubMed1998

Peroral gene therapy of lactose intolerance using an adeno-associated virus vector.

Gene therapy is usually reserved for severe and medically refractory disorders because of the toxicity, potential long-term risks and invasiveness of most gene transfer protocols. Here we show that an orally administered adeno-associated viral vector leads to persistent expression of a beta-galactosidase transgene in both gut epithelial and lamina propria cells, and that this approach results in long-term phenotypic recovery in an animal model of lactose intolerance. A gene 'pill' associated with highly efficient and stable gene expression might be a practical and cost-effective strategy for even relatively mild disorders, such as lactase deficiency.

Administration, Oral↗
PubMed1998

An automated fluorescent PCR method for detection of shiga toxin-producing Escherichia coli in foods.

An automated fluorescence-based PCR system (a model AG-9600 AmpliSensor analyzer) was investigated to determine whether it could detect Shiga toxin-producing Escherichia coli (STEC). The AmpliSensor PCR assay involves amplification-mediated disruption of a fluorogenic DNA signal duplex (AmpliSensor) that is homologous to conserved target sequences in a 323-bp amplified fragment of Shiga toxin genes stx1, stx2, and stxe. Using the Amplisensor assay, we detected 113 strains of STEC belonging to 50 different serotypes, while 18 strains of non-Shiga-toxin-producing E. coli and 68 strains of other bacteria were not detected. The detection limits of the assay were less than 1 to 5 CFU per PCR mixture when pure cultures of five reference strains were used and 3 CFU per 25 g of food when spiked ground beef samples that were preenriched overnight were used. The performance of the assay was also evaluated by using 53 naturally contaminated meat samples and 48 raw milk samples. Thirty-two STEC-positive samples that were confirmed to be positive by the culture assay were found to be positive when the AmpliSensor assay was used. Nine samples that were found to be positive when the PCR assay was used were culture negative. The system described here is an automated PCR-based system that can be used for detection of all serotypes of STEC in food or clinical samples.

Animals↗
PubMed1998

Monoclonal antibodies to distinct sites on herpes simplex virus (HSV) glycoprotein D block HSV binding to HVEM.

HVEM (for herpesvirus entry mediator) is a member of the tumor necrosis factor receptor superfamily and mediates entry of many strains of herpes simplex virus (HSV) into normally nonpermissive Chinese hamster ovary (CHO) cells. We used sucrose density centrifugation to demonstrate that purified HSV-1 KOS virions bind directly to a soluble, truncated form of HVEM (HVEMt) in the absence of any other cell-associated components. Therefore, HVEM mediates HSV entry by serving as a receptor for the virus. We previously showed that soluble, truncated forms of HSV glycoprotein D (gDt) bind to HVEMt in vitro. Here we show that antibodies specific for gD, but not the other entry glycoproteins gB, gC, or the gH/gL complex, completely block HSV binding to HVEM. Thus, virion gD is the principal mediator of HSV binding to HVEM. To map sites on virion gD which are necessary for its interaction with HVEM, we preincubated virions with gD-specific monoclonal antibodies (MAbs). MAbs that recognize antigenic sites Ib and VII of gD were the only MAbs which blocked the HSV-HVEM interaction. MAbs from these two groups failed to coprecipitate HVEMt in the presence of soluble gDt, whereas the other anti-gD MAbs coprecipitated HVEMt and gDt. Previous mapping data indicated that site VII includes amino acids 11 to 19 and site Ib includes 222 to 252. The current experiments indicate that these sites contain residues important for HSV binding to HVEM. Group Ib and VII MAbs also blocked HSV entry into HVEM-expressing CHO cells. These results suggest that the mechanism of neutralization by these MAbs is via interference with the interaction between gD in the virus and HVEM on the cell. Group Ia and II MAbs failed to block HSV binding to HVEM yet still neutralized HVEM-mediated entry, suggesting that these MAbs block entry at a step other than HVEM binding.

Animals↗
PubMed1998

HveA (herpesvirus entry mediator A), a coreceptor for herpes simplex virus entry, also participates in virus-induced cell fusion.

The purpose of this study was to determine whether a cell surface protein that can serve as coreceptor for herpes simplex virus type 1 (HSV-1) entry, herpesvirus entry mediator (previously designated HVEM but renamed HveA), also mediates HSV-1-induced cell-cell fusion. We found that transfection of DNA from KOS-804, a previously described HSV-1 syncytial (Syn) strain whose Syn mutation was mapped to an amino acid substitution in gK, induced numerous large syncytia on HveA-expressing Chinese hamster ovary cells (CHO-HVEM12) but not on control cells (CHO-C8). Antibodies specific for gD as well as for HveA were effective inhibitors of KOS-804-induced fusion, consistent with previously described direct interactions between gD and HveA. Since mutations in gD determine the ability of HSV-1 to utilize HveA for entry, we examined whether the form of virally expressed gD also influenced the ability of HveA to mediate fusion. We produced a recombinant virus carrying the KOS-804 Syn mutation and the KOS-Rid1 gD mutation, which significantly reduces viral entry via HveA, and designated it KOS-SR1. KOS-SR1 DNA had a markedly reduced ability to induce syncytia on CHO-HVEM12 cells and a somewhat enhanced ability to induce syncytia on CHO-C8 cells. These results support previous findings concerning the relative abilities of KOS and KOS-Rid1 to infect CHO-HVEM12 and CHO-C8 cells. Thus, HveA mediates cell-cell fusion as well as viral entry and both activities of HveA are contingent upon the form of gD expressed by the virus.

Animals↗