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Biomedical subjects

R Sun

Publications and source records attributed to R Sun.

At least 109 records · Page 6Linked to original sources

Beta cyclodextrins enhance adenoviral-mediated gene delivery to the intestine.

PURPOSE: In general, the intestinal epithelium is quite refractory to viral and non-viral methods of gene transfer. In this report, various cyclodextrin formulations were tested for their ability to enhance adenoviral transduction efficiency in two models of the intestinal epithelium: differentiated Caco-2 cells and rat jejunum. METHODS: Transduction efficiency of replication-deficient adenovirus type 5 vectors encoded with either the E. coli beta-galactosidase or the jellyfish green fluorescent protein gene was assessed by X-gal staining or visualization of fluorescence 48 hours after infection. In vivo experiments were performed using an intestinal loop ligation technique. RESULTS: Several formulations of neutral and positively charged beta cyclodextrins significantly enhanced adenoviral-mediated gene transfer in the selected models. The cyclodextrin formulations studied increased adenoviral transduction in the intestine by enhancing both viral binding and internalization. Viral binding was significantly increased on cell membranes treated with positively charged cyclodextrins, as seen with confocal microscopy and rhodamine-labeled virus. Permeability studies and TEER readings revealed that the most successful formulations gently disrupt cell membranes. This enhances internalization of viral particles and results in increased levels of gene expression. CONCLUSIONS: These formulations can be of value in gene transfer to cells and tissues in which adenoviral infection is limited due to a lack of fiber and alpha(v) integrin receptors. They are simple to prepare and do not affect the ability of the virus to transduce target cells.

Adenoviridae↗

High prevalence of antibodies to human herpesvirus 8 in relatives of patients with classic Kaposi's sarcoma from Sardinia.

A survey for antibodies to a recombinant small viral capsid antigen (sVCA) of human herpesvirus type 8 (HHV-8) was conducted in Sardinia, one of the world's highest incidence areas for classic Kaposi's sarcoma (KS). Prevalence of antibodies to HHV-8 sVCA was greatest in patients with KS (95%), followed by family members (39%) and a Sardinian control population age- and sex-matched to the relatives (11%). Within families, prevalence of antibodies was about equal among spouses, children, and siblings of KS patients, a finding that raises the possibilities of intrafamilial person-to-person or vertical transmission. Antibodies were detected 2-3 times more frequently in males than in females. The data show that prevalence of antibodies to HHV-8 sVCA correlates with the distribution of classic KS in a high- incidence area. Clustering of seroprevalence within some families suggests the presence of familial risk factors for active HHV-8 infection.

Age Factors↗

Expression of mucin-type glycoprotein K88 receptors strongly correlates with piglet susceptibility to K88(+) enterotoxigenic Escherichia coli, but adhesion of this bacterium to brush borders does not.

Three antigenic variants of the K88 fimbrial adhesin exist in nature, K88ab, K88ac, and K88ad. Enterotoxigenic Escherichia coli (ETEC) strains that produce these fimbriae cause life-threatening diarrhea in some but not all young pigs. The susceptibility of pigs to these organisms has been correlated with the adherence of bacteria to isolated enterocyte brush borders. Whether that correlation holds for multiple K88 variants and over a broad genetic base of pigs is unknown and was the impetus for this study. We also desired to examine the correlation of the expression of a porcine intestinal brush border mucin-type glycoprotein (IMTGP) which binds K88ab and K88ac with the susceptibility of piglets to K88(+) ETEC. Of 31 neonatal gnotobiotic pigs inoculated with K88ab+ or K88ac+ ETEC, 13 developed severe diarrhea, became dehydrated, and died or became moribund. Another pig became severely lethargic but not dehydrated. In vitro brush border adherence analysis was not possible for 10 of the severely ill pigs due to colonization by challenge strains. However, of the 17 pigs that did not become severely ill, 8 (47%) had brush borders that supported the adherence of K88ab+ and K88ac+ bacteria in vitro, suggesting a poor correlation between in vitro brush border adherence and piglet susceptibility to K88(+) ETEC. By contrast, the expression of IMTGP was highly correlated with susceptibility to K88(+) ETEC. Of the 12 pigs that produced IMTGP, 11 developed severe diarrhea. The other pig that produced IMTGP became lethargic but not severely diarrheic. Only 2 of 18 pigs that did not produce IMTGP became severely diarrheic. Colonizing bacteria were observed in histologic sections of intestines from all pigs that expressed IMTGP except for the one that did not develop severe diarrhea. However, colonizing bacteria were observed in histologic sections from only one pig that did not produce IMTGP. The bacterial concentration in the jejuna and ilea of pigs expressing IMTGP was significantly greater (P < 0.005) than that in pigs not expressing IMTGP. These observations suggest the IMTGP is a biologically relevant receptor for K88ab+ and K88ac+ E. coli or a correlate for expression for such a receptor.

Animals↗

Ultrasensitive reverse transcription-PCR assay for quantitation of human immunodeficiency virus type 1 RNA in plasma.

With the recent introduction of combination therapy, human immunodeficiency virus type 1 (HIV-1) RNA levels in plasma have been dramatically reduced, frequently to below the limit of quantitation (400 copies/ml of plasma) of the AMPLICOR HIV-1 MONITOR Test (Roche Diagnostic Systems). To achieve enhanced sensitivity of the AMPLICOR HIV-1 MONITOR Test, a modified specimen preparation procedure that allows input of RNA from 10-fold more plasma per amplification reaction was developed. This "ultrasensitive" method allows the accurate quantitation of plasma HIV-1 RNA levels as low as 50 copies/ml. A precision study yielded average within-run and between-run coefficients of variation (CV) of 24.8 and 9.6%, respectively. A multicenter reproducibility study demonstrated that the laboratory-to-laboratory reproducibility of this assay is good, with an average CV of 32%. The linear range of this test is between 50 and 50,000 copies/ml of plasma. RNA concentrations measured by the ultrasensitive and standard HIV-1 MONITOR tests exhibited good agreement within the shared linear range of the two methods. The two measurements were within a factor of 2 for 91% of the specimens tested, with the concentration measured by the ultrasensitive method being only slightly lower (median, 22% lower). Preliminary studies suggest that this assay will prove to be useful for predicting the stability of viral suppression in patients whose RNA levels drop below 400 copies/ml in response to highly active antiretroviral therapy.

Acquired Immunodeficiency Syndrome↗

Evaluation of a commercial PCR kit for diagnosis of cytomegalovirus infection of the central nervous system.

We evaluated the AMPLICOR cytomegalovirus (CMV) PCR kit for the diagnosis of neurologic CMV infections on 43 positive and 112 negative archived cerebrospinal fluid specimens originally tested by an in-house PCR method. The AMPLICOR kit showed sensitivity and specificity of 95 and 100%, respectively, versus the home-grown assay, indicating its utility in this clinical setting.

Base Sequence↗

Evaluation of the AMPLICOR cytomegalovirus test with specimens from human immunodeficiency virus-infected subjects.

The AMPLICOR cytomegalovirus (CMV) test, a new qualitative assay for the detection of CMV DNA in plasma, was compared to conventional methods and quantitative PCR (Q-PCR) assays by using leukocytes and plasma from 179 blood samples from subjects with AIDS. For the diagnosis of CMV disease, cell-based assays such as a Q-PCR with polymorphonuclear leukocytes (Q-PCR-PMNL) and a pp65 antigenemia assay had the highest sensitivities but suffered from a lack of specificity. The best agreement between the results of the Q-PCR-PMNL assay and those of the AMPLICOR test was found when a threshold diagnostic value of 690 copies per 10(5) cells was selected for the Q-PCR-PMNL assay. In that context, the AMPLICOR CMV test had a sensitivity of 96.4% and a specificity of 95.3% when results were compared to results of the cell-based PCR assay. This threshold was close to the one described as associated with the best sensitivity and specificity for the diagnosis of CMV disease in a recently published study (4). Blood samples that tested positive by the Q-PCR-PMNL assay but negative by the AMPLICOR CMV test were associated with viral loads (mean, 785 copies, median, 96 copies per 10(5) leukocytes) lower than the viral loads of blood samples that tested positive by both assays (mean, 21,452 copies; median, 9,784 copies per 10(5) leukocytes) (P = 0.003). The AMPLICOR CMV test gave positive results at least 48 days before the development of symptomatic CMV disease in a longitudinal analysis of a limited subset of patients (n = 6) from whom sequential specimens were available for testing. In conclusion, the AMPLICOR CMV test is a very convenient assay combining rapidity, simplicity, and the possibility of batch testing. A positive result by this test seems particularly important since this implies, in most instances, the presence or the imminence of CMV disease, although a negative test result does not rule out disease.

AIDS-Related Opportunistic Infections↗

[The predominant expression of Th2 type cytokines in human tumor cells].

OBJECTIVE: To observe the expression of Th1 versus Th2 type cytokines in human tumor cells. METHODS: The gene expression of Th1/Th2 cytokines in human tumor cells was detected by RT-PCR and RNA dot hybridization using IL-2 and IFN gamma as Th1 type cytokine genes, IL-4, IL-10 and IL-13 as Th2 type cytokine genes. RESULTS: There were predominant expressions of Th2 type cytokines in 20 different human tumor cell lines including 11 solid tumor and 9 hematogenous tumor cells. CONCLUSION: Predominant expression of Th2 type cytokines by tumor cells may be related to the evasion of tumor cells from immune surveillance.

Breast Neoplasms↗

In vitro evaluation of the efficacy of the capsular tension ring for managing zonular dialysis in cataract surgery.

BACKGROUND AND OBJECTIVE: In vitro evaluation of the capsular tension ring for managing zonular dialysis in cataract surgery. MATERIALS AND METHODS: Pig and cadaver eye models were used in this study. Lens material was removed with phacoemulsification, then the zonules were cut in one quadrant of the meridian to induce capsular bag decentration. Posterior chamber intraocular lenses (PC IOLs) were implanted into the bag with or without the tension rings. The IOL and the tension ring positions were viewed using the Miyaki technique. PC IOLs were also implanted into isolated capsular bags with or without tension rings, and bag configuration was examined. RESULTS: The IOL decentration was observed when the IOLs were implanted into the eyes without zonular support in one quadrant of the meridian. No IOL decentration was observed when the tension ring and the IOL were implanted together. When only the IOLs were inserted into the isolated bags they became oval, whereas the circular bags were preserved when both the IOL and the tension ring were placed in-the-bag. CONCLUSION: The authors' in vitro model demonstrated that the capsular tension ring maintained the circular contour of the capsular bag and IOL centration in the eyes with broken zonules. The results suggest that capsular tension rings may provide an alternative means to manage zonular dialysis during phacoemulsification and PC IOL implantation.

Animals↗

[Determination enzyme protein of CK-MB m-AST and ChE by immunological methods and survey of its applying values].

In recent decades, because considerable progress has been made due to rapid developments in basic theory and techniques in molecular biology and immunology, the determination of trace enzyme proteins is not difficult. We measured the serum concentration of Creatine kinase-MB (CK-MB) mitochondria aspartate aminotransferase (m-AST) and cholinesterase (ChE) immunologically and compared these findings with those of an assay of enzyme activity. Purification of enzyme protein and preparation of serum antibodies monoclonal antibodies established the immunological assay methods. Equipment and reagents for enzyme activity test use 7150 Biochemical Analyzer. CK-NAC AST and ChE were produced by trace kits (Australia). CK-MB and m-AST use immunological inhibition method. CK-MB m-AST ChE of protein determination used immunological turbidimetry. The normal group included 150 cases and the 1990 patient group. Results of the two methods did not significantly differ for normal controls, but were significantly different in the patient group. These results demonstrated that the two methods differ, although each may have specific clinical significance. How to evaluate these differences needs to be studied further, but immunological assay uses higher values for clinical diagnosis than enzyme activity assay.

Antibodies, Monoclonal↗

The locus of Epstein-Barr virus terminal repeat processing is bound with enhanced affinity by Sp1 and Sp3.

EBV DNA contains G-rich, repeat regions that are involved in rearrangement and recombination events including terminal repeat (TR) processing and the EBNA-2 deletion in the EBV strain P3HR-1. Cellular proteins, called terminal or tandem repeat binding proteins (TRBPs), recognize sequences at the junctions of these recombination events. In this study, using antibody supershift assays and expression of recombinant proteins, we show that Sp1 and Sp3 are the sequence-specific components of TRBP and that Ku is the nonspecific binding component. Sp1 binds other recombinogenic regions of EBV DNA, but Sp3 does not bind to the large internal repeat. The sequence GGGGTGGGG, a low affinity site for Sp1 and Sp3, is the minimal binding site within terminal repeat binding site 1 (TRBS1). However, 3' flanking sequences in the sequence GGGGTGGGGCATGGGG augment binding of Sp1 and Sp3 so that their affinity of binding is increased approximately twofold relative to a classical high-affinity Sp1 site. EBV lytic cycle induction does not alter the abundance or binding activity of any of the three identified components of TRBP. Sp1 and Sp3 may act in trans to promote EBV terminal repeat processing and possibly other viral and cellular recombination events.

DNA-Binding Proteins↗

Temporal trends and factors associated with survival after Pneumocystis carinii pneumonia in California, 1983-1992.

The authors investigated quarterly trends in survival after the diagnosis of Pneumocystis carinii pneumonia for 19,607 patients in California in the decade from January 1, 1983, through December 31, 1992. Subjects included all cases for whom P. carinii pneumonia was the initial (and only) acquired immunodeficiency syndrome (AIDS)-defining diagnosis as reported to the California human immunodeficiency virus/AIDS surveillance registry. There was a period of rapidly improving survival from approximately June 1986 until April 1988, coincident with the widespread introduction of antiretroviral therapy (zidovudine) and the institution of P. carinii pneumonia prophylaxis (with cotrimoxazole and pentamidine). There was no evidence, however, of meaningful improvements in survival for these patients after that period. The association of several covariates (risk transmission group, gender, race/ethnicity, certainty of P. carinii pneumonia diagnosis, age, region of residence, availability of CD4 count, and level of CD4 count) were also studied both by proportional hazards regression and by recursive partitioning (i.e., tree-based) survival analysis. The availability of a CD4 count (regardless of its level) was the single factor most strongly associated with survival (median survival 36 months among those with and 14 months among those without reported CD4 counts, p < 0.05). Data from this large, population-based surveillance registry of AIDS in California suggest that, despite earlier improvements in survival after the diagnosis of P. carinii pneumonia, the long-term survival of these patients remains poor (39% alive 2 years after diagnosis) and that no improvement in survival has occurred since 1988.

AIDS-Related Opportunistic Infections↗

The transcriptional activator Sp1, a novel autoantigen.

OBJECTIVE: To identify one nuclear autoantigenic protein within a complex of DNA binding proteins that bind to GC-rich sequences in Epstein-Barr virus and cellular DNA, and to describe the clinical characteristics of patients whose sera contained autoantibodies to this novel autoantigen. METHODS: Antibodies to autoantigen Sp1 were initially measured by an electrophoretic mobility shift assay to detect DNA binding proteins. Nuclear extracts and purified Sp1 protein were used in these assays. Recognition of the autoantigen by autoimmune sera was confirmed by immunoprecipitation and immunoblotting. RESULTS: The autoantigen was identified as Sp1. Anti-Sp1 was detected in sera from 8 (3%) of 230 patients. These sera contained antinuclear antibodies, but lacked antibodies to double-stranded DNA or to several extractable nuclear antigens. The patients whose sera contained antibodies to Sp1 were white women with fatigue, arthritis, Raynaud's phenomenon, malar rash, and photosensitivity. CONCLUSION: Sp1 is the first described example of an RNA polymerase II transcription activator as an autoantigen. The presence of Sp1 autoantibodies is associated with undifferentiated connective tissue disease.

Adult↗

gp120, a human immunodeficiency virus-1 coat protein, augments excitotoxic hippocampal injury in perinatal rats.

Recent data suggest that gp120, a human immunodeficiency virus-1 (HIV-1) coat glycoprotein that is secreted by HIV-infected cells, is neurotoxic, and that this toxicity is mediated, at least in part, by activation of N-methyl-D-aspartate-type excitatory amino acid receptors. To test this hypothesis in vivo, we examined the neurotoxicity of gp120 injected intrahippocampally, alone or co-injected with the selective excitatory amino acid agonist N-methyl-D-aspartate, in seven-day-old rats. Severity of injury in the lesioned hippocampus was assessed five days later, using three outcome measures: histopathology, hippocampal atrophy (derived from regional cross-sectional area measurements) and loss of [3H]glutamate receptor binding (based on in vitro autoradiography assays). To confirm that any observed effects were attributable to gp120 bioactivity, each group of experiments included controls that received equal amounts of heat-treated gp120. Gp120 (200 ng) elicited minimal focal pyramidal cell loss immediately adjacent to the injection track; there was no hippocampal atrophy or loss of [3H]glutamate binding. Co-injection of 50 ng gp120 with N-methyl-D-aspartate (5 nmol, threshold excitotoxic dose) increased the severity of hippocampal injury; hippocampal atrophy was greater in animals that received injections of 5 nmol N-methyl-D-aspartate in combination with 50 ng gp120 than in those that received either N-methyl-D-aspartate alone (5 nmol) or 5 nmol N-methyl-D-aspartate+50 ng heat-treated gp120 (mean+/-S.E.M. percentage reduction in injected hippocampal volume vs contralateral: N-methyl-D-aspartate, -19+/-3; N-methyl-D-aspartate+gp120, -26.8+/-2.1; N-methyl-D-aspartate+heat-treated gp120, -14.0+/-2.2; P<0.001, ANOVA). Treatment with the competitive N-methyl-D-aspartate antagonist 3-((RS)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (20mg/kg) markedly reduced the severity of injury elicited by the combination of gp120 with N-methyl-D-aspartate. These data support the hypothesis that locally secreted gp120 could exert neurotoxic effects, mediated by N-methyl-D-aspartate receptor activation, in vivo in the immature brain.

Animals↗

The effect of timing of ondansetron administration in outpatients undergoing otolaryngologic surgery.

A randomized, double-blind, placebo-controlled study was designed to compare the relative efficacy of prophylactic ondansetron, 4 mg intravenously (IV), when administered before induction of anesthesia or at the end of surgery to an outpatient population at high risk of developing postoperative nausea and vomiting (PONV). Patients undergoing otolaryngologic surgery were randomly assigned to one of three different treatment groups: Group 1 (placebo) received saline 5 mL prior to induction of anesthesia and again at the end of surgery; Group II received ondansetron 4 mg in 5 mL prior to induction of anesthesia and saline 5 mL at the end of surgery; and Group III received saline 5 mL prior to induction of anesthesia and ondansetron 4 mg at the end of surgery. All patients received the same general anesthetic technique. A standardized regimen of rescue antiemetics was administered in the recovery room to patients with > or = 2 emetic episodes or at the patients request for persistent nausea. Episodes of nausea and vomiting, as well as the need for rescue antiemetics, were recorded for 24 h after the operation. The incidences of nausea and emesis in the recovery room after prophylactic ondansetron, 4 mg IV, administered either before induction (68% and 20%, respectively) or at the end of surgery (60% and 4%, respectively) were not significantly decreased compared to the placebo control group (80% and 12%, respectively). However, when ondansetron was administered at the end of the operation, it significantly reduced the need for rescue antiemetics in the recovery room (36% vs 64% in the control group). The postanesthesia care unit and hospital discharge times were similar in all three study groups. One patients in Group II and one patient in Group III were hospitalized because of intractable symptoms related to PONV. After discharge from the ambulatory surgery unit, the incidence of nausea, vomiting, and the need for rescue antiemetic drugs were similar in all three treatment groups. In conclusion, ondansetron (4 mg IV) was more effective in reducing the need for rescue antiemetics in the recovery room when administered at the end versus prior to the start of otolaryngologic surgery. Therefore, when ondansetron is used for antiemetic prophylaxis in outpatients undergoing otolaryngologic procedures, it should be administered at the end of the operation rather than prior to induction of anesthesia.

Adult↗

Detection of hepatitis C by RT-PCR in formalin-fixed paraffin-embedded tissue from liver transplant patients.

The histopathologic alterations of hepatitis C virus (HCV) infection of the liver overlap with those of other diseases, making interpretation of liver biopsy specimens in some cases insufficient to render a diagnosis. Although HCV infection can be confirmed by detection of circulating anti-HCV antibodies, immunocompromised liver transplant recipients are often unable to mount an immunologic response to the virus, resulting in false-negative serologic testing. We describe the comparison of reverse transcription-polymerase chain reaction (RT-PCR) with histopathology, serology, and immunohistochemistry for the diagnosis of HCV. Sixty-three formalin-fixed, paraffin-embedded tissue samples (40 needle biopsy specimens and 23 native liver resection specimens) from 35 transplant patients were analyzed by use of a novel method of RNA extraction followed by nested PCR for HCV as well as albumin mRNA as an internal control. HCV was detected by RT-PCR in 50 of 51 (98%) paraffin sections of liver from transplant patients with circulating anti-HCV antibodies, 15 of which lacked characteristic histologic features of HCV infection. Overall, there were no false-negative results in 36 needle biopsy specimens from patients with hepatitis C infection, but three negative results were seen in end-stage cirrhotic native livers resected from HCV-infected patients. No false-positive test results were seen among 21 negative controls (10 liver samples from immunocompetent patients with abnormalities unrelated to hepatitis C and 11 liver biopsies from immunocompetent patients without histologic evidence of liver disease). In comparison, immunohistochemistry using antibody TORDJI-22 was positive for HCV in only 15 of 32 (47%) needle biopsies positive by RT-PCR. Our results indicate that RT-PCR is a more sensitive and specific method of detecting hepatitis C in routinely processed paraffin sections of formalin-fixed liver biopsy specimens than histopathologic examination or immunohistochemistry.

Formaldehyde↗

Selective switch between latency and lytic replication of Kaposi's sarcoma herpesvirus and Epstein-Barr virus in dually infected body cavity lymphoma cells.

The BC-1 cell line, derived from a body cavity-based, B-cell lymphoma, is dually infected with Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In these studies, the relationships between these two gammaherpesviruses and BC-1 cells were characterized and compared. Single-cell cloning experiments suggested that all BC-1 cells contain both genomes. In more than 98% of cells, both viruses were latent. The two viruses could be differentially induced into their lytic cycles by chemicals. EBV was activated into DNA replication and late-gene expression by the phorbol ester tetradecanoyl phorbol acetate (TPA). KSHV was induced into DNA replication and late-gene expression by n-butyrate. Amplification of both EBV and KSHV DNAs was inhibited by phosphonoacetic acid. Induction of the KSHV lytic cycle by n-butyrate was accompanied by the disappearance of host-cell beta-actin mRNA. Induction of EBV by TPA was not accompanied by such an effect on host-cell gene expression. Induction of the KSHV lytic cycle by n-butyrate was associated with the expression of several novel polypeptides. Recognition of one of these, p40, served as the basis of development of an assay for antibodies to KSHV in the sera of infected patients. BC-1 cells released infectious EBV; however, there was no evidence for the release of encapsidated KSHV genomes by BC-1 cells, even though n-butyrate-treated cells contained numerous intranuclear nucleocapsids. The differential inducibility of these two herpesviruses in the same cell line points to the importance of viral factors in the switch from latency to lytic cycle.

Animals↗

Identification, expression, and immunogenicity of Kaposi's sarcoma-associated herpesvirus-encoded small viral capsid antigen.

We describe a recombinant antigen for use in serologic tests for antibodies to Kaposi's sarcoma (KS)-associated herpesvirus (KSHV). The cDNA for a small viral capsid antigen (sVCA) was identified by immunoscreening of a library prepared from the BC-1 body cavity lymphoma cell line induced into KSHV lytic gene expression by sodium butyrate. The cDNA specified a 170-amino-acid peptide with homology to small viral capsid proteins encoded by the BFRF3 gene of Epstein-Barr virus and the ORF65 gene of herpesvirus saimiri. KSHV sVCA was expressed from a 0.85-kb mRNA present late in lytic KSHV replication in BC-1 cells. This transcript was sensitive to phosphonoacetic acid and phosphonoformic acid, inhibitors of herpesvirus DNA replication. KSHV sVCA expressed in mammalian cells or Escherichia coli or translated in vitro was recognized as an antigen by antisera from KS patients. Rabbit antisera raised to KSHV sVCA expressed in E. coli detected a 22-kDa protein in KSHV-infected human B cells. Overexpressed KSHV sVCA purified from E. coli and used as an antigen in immunoblot screening assay did not cross-react with EBV BFRF3. Antibodies to sVCA were present in 89% of 47 human immunodeficiency virus (HIV)-positive patients with KS, in 20% of 54 HIV-positive patients without KS, but in none of 122 other patients including children born to HIV-seropositive mothers and patients with hemophilia, autoimmune disease, or nasopharyngeal carcinoma. Low-titer antibody was detected in three sera from 28 healthy subjects. Antibodies to recombinant sVCA correlate with KS in high-risk populations. Recombinant sVCA can be used to examine the seroepidemiology of infection with KSHV in the general population.

AIDS-Related Opportunistic Infections↗

Sp1 binds to the precise locus of end processing within the terminal repeats of Epstein-Barr virus DNA.

Interconversion between the linear genome of Epstein-Barr virus (EBV) present in virions and intracellular circular EBV DNA is a novel DNA recombination process. A previously characterized DNA binding activity called terminal repeat or tandem repeat binding protein (TRBP) was found to recognize several G-rich recombinogenic sequences in the EBV genome and in cellular DNA. TRBP was also found to be an autoantigen recognized by sera from certain patients with undifferentiated connective-tissue disorders. Here the transcription factor Sp1 has been identified as a component of TRBP and has been shown to be an autoantigen. Sp1 bound to recombination junctions of EBV DNA, such as those in the terminal repeats and in the large internal repeats, as well as to recombinogenic regions of cellular DNA, such as variable-number tandem repeats and switch regions of the immunoglobulin genes. We defined the ends of the linear EBV genome present in virions and showed that Sp1 binds to the sequence (GGGGTGGGGCATGGG) within EBV terminal repeats at the precise locus of interconversion of linear and circular viral DNA. Sp1 may be involved in DNA recombination.

Animals↗