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Results for “Genomic subtypes”

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PubMed1985

A clone of hepatitis B virus (subtype adr) DNA with a new HindIII site.

We have cloned the HBV genome subtype adr through its HindIII site into plasmid pBR322. Twelve recombinant plasmids each with an insert of the HBV genome were obtained. The restriction map of one of the recombinants, plasmid pADR-H1, was analyzed. The location of the sites for BamHI, BglI, BglII, SstII, XbaI and XhoI in pADR-H1 were found to be the same as that in pADR-1, but the HindIII site of pADR-H1 is distinctly different from that of pADR-1. The BamHI-HindIII fragment is 316 bp long in the genome of pADR-1. However, it is only 82 bp in pADR-H1. No deletion of sequence between BamHI and HindIII sites has been found in the HBV genome of pADR-H1. The sequencing data around the HindIII site of pADR-H1 in both pADR-H1 and pADR-1 showed that there is a stretch of AAGTTT in pADR-1 compared to an AAGCTT in pADR-H1. In addition, other differences were found. There are three sites for AvaI, four for HincII, one for HpaI and none for SphI in the genome of pADR-H1 compared to four sites for AvaI, three for HincII, one for SphI and none for HpaI in pADR-1. The biological significance of base pair mutation in HBV DNA and the possibility of the existence of HindIII site in the genome of subtypes ayw and adw were discussed.

Base Sequence↗

PubMed2001

Characterization of full-length HIV type 1 subtype C sequences from South Africa.

Four full-length genome subtype C sequences from South Africa, three of which are being used for vaccine development, were characterized. Three isolates were obtained from recently infected individuals in KwaZulu/Natal: Du151, Du422, and Du179. A fourth isolate, CTSc2, was obtained from an individual residing in Cape Town. All four strains used the CCR5 coreceptor, although Du179 also used CXCR4. The four isolates clustered within subtype C, but the three Du isolates formed a subcluster with a bootstrap value of 100%, with CTSc2 outside the subcluster. None of the strains showed evidence of intersubtype recombination, as expected from the predominance of subtype C in South Africa. All 4 isolates had a 16-amino acid truncation on the 3' end of the Rev protein, identified in other subtype C isolates. Like many other subtype C strains, Du151, Du422, and Du179 had three NF-kappa B-binding sites in the LTR; however, CTSc2 had only two.

Genome, Viral↗

PubMed2003

[Analysis of subtype of porcine endogenous retrovirus in two species of Chinese pigs].

OBJECTIVE: To analyze the subtype of porcine endogenous retrovirus (PERV) in two species of Chinese pigs-Wu zhishan pig and Banna minipig inbred; the total number of pigs being eighty six. METHODS: Three primers which are specific for the three PERV subtypes (subtypes A, B and C) were used to amplify the genome DNA extracted from the pigs. RESULTS: In all tested pigs' genome, subtype C was not found; in 77.9% pigs, double positive envAB were found; in 22.1% pigs, only A or B was found. CONCLUSION: In the genome of peripheral leukocytes from Wuzhishan pig and Banna minipig inbred, only subtypes A and B exist, and envAB predominate.

Animals↗

PubMed1998

Molecular epidemiology of adenovirus type 7 in Israel: identification of two new genome types, Ad7k and Ad7d2.

The molecular epidemiology of Adenovirus type 7 in Israel was investigated. Fifty-seven adenovirus isolates identified as serotypes 7 or 7a which were recovered from patients in Israel between 1968 and 1995 were analyzed by restriction enzymes digestion using BamHI for primary discrimination and identification of genome types and by six additional enzymes: BstEII, HpaI, BglI, BglII, BclI, and XbaI for confirmation and determination of genomic subtypes. Four digestion patterns were identified with BamHI; one of them was new. Using BstEII, two patterns were obtained, one of them new. Digestion with the other five enzymes yielded known patterns. The analysis revealed four different genomic types and subtypes, which circulated in Israel in different years: subtype 7a1; type 7b, a type with a new BamHI pattern which was designated type 7K, and a subtype with a new BstEII pattern which differed from type 7d by one restriction site and was designated type 7d2. Twenty-two isolates from 1968 through 1975 and from 1984 were Ad7a1. Three isolates from 1973-1974 were Ad7b. Five isolates from 1968 through 1973 were Ad7K and 27 isolates from 1992 through 1995 were Ad7d2. This demonstrates the temporal change in the circulating genome types with up to three genome types cocirculating in 1 year (1973). The two new types, Ad7k and Ad7d2 could have evolved in Israel or could have been imported by travellers and immigrants from neighboring or distant countries.

Adenovirus Infections, Human↗

PubMed1995

Prevalence and distribution of BK virus subtypes in healthy people and immunocompromised patients detected by PCR-restriction enzyme analysis.

BACKGROUND: Four antigenic subtypes of BK virus (BKV) have recently been characterised by both genomic subtyping and serological reactivity. OBJECTIVES: To study the prevalence and distribution of subtypes of BKV in different groups of patients. STUDY DESIGN: Urine specimens were collected from 33 bone marrow transplant (BMT) recipients, from 101 HIV-infected patients, from 15 children aged 2-5 and from 40 pregnant women were tested for BKV DNA by polymerase chain reaction (PCR) and subtyped using a PCR-sequencing (PCR-S) and a modified PCR-restriction enzyme analysis (PCR-RE) methods. RESULTS: BKV DNA was detected in 12/18 (67%) of BMT patients with haematuria and 5/15 (33%) without. Overall BKV DNA was detected in 45% of HIV-infected patients, the prevalence of BKV DNA increased with greater immunosuppression as defined by CD4 cell counts. BKV DNA was detected in urine samples from 27% of children and 47% of pregnant women. Four stable BKV subtypes were detected in these patient groups. Dual infections with more than one subtype were identified in urine samples from HIV-infected patients, children and pregnant women but not in the samples from bone marrow recipients. CONCLUSION: This study has confirmed the high prevalence of BKV infection in immunocompromised patients and suggests that stable BKV subtypes with conserved sequences are circulating in the human population. The techniques of PCR-S and PCR-RE described in this study are sufficiently sensitive for subtyping BKV direct from clinical specimens.

Journal Article↗

PubMed1988

Characterization of the genome of equine herpesvirus 1 subtype 2.

The genome structure of equine herpesvirus 1 (EHV-1) subtype 2 was shown by electron microscopic studies and restriction endonuclease site mapping to comprise two covalently linked segments (L, 109 kbp; S, 35 kbp). The S segment contains a unique sequence (US) flanked by a substantial inverted repeat (TRS/IRS). Thus, the genome structure of EHV-1 subtype 2 is similar to that published previously for EHV-1 subtype 1, but the two subtypes differ in the occurrences of EcoRI and BamHI restriction sites. Hybridization studies using cloned EHV-1 DNA showed that the genome of EHV-1 subtype 2 is colinear with the genomes of EHV-1 subtype 1 and herpes simplex virus type 1. DNA sequence data for four EHV-1 subtype 2 genes, including one potentially encoding a glycoprotein, were obtained by sequencing a 4574 bp BamHI fragment containing the junction between US and TRS. The genome structure, hybridization and sequence data confirm that EHV-1 subtype 2 is of the alphaherpesvirus lineage.

Amino Acid Sequence↗

PubMed1994

Comparison of PCR-based restriction length polymorphism analysis of urease genes with rRNA gene profiling for monitoring Helicobacter pylori infections in patients on triple therapy.

Multiple isolates of Helicobacter pylori from antral biopsies of nine patients were examined by DNA fingerprinting. Analysis of rRNA gene patterns and HaeIII restriction fragment length polymorphism of PCR-amplified urease genes were compared and used to study colonization before and after failed triple therapy. H. pylori isolates from a single biopsy shared the same HaeIII DNA fingerprint regardless of the isolation method (plate or broth). DNA pattern types of paired strains of H. pylori were distinct between patients and were not grossly affected by treatment except for one patient with an altered strain type. H. pylori infections were generally associated with several subpopulations of strains, evident from the subtypic variation before and after treatment, detectable by both DNA fingerprinting methods. The urease gene patterns also provided evidence that some cultures of H. pylori probably contained a mixture of genomic subtypes. The study suggests that triple therapy has the effect either of inducing minor genomic variations or of changing the proportions of different subtypes of H. pylori. It was concluded that urease gene profiling provides a simple yet reliable method of establishing whether treatment failures are attributable to incomplete eradication of H. pylori.

Anti-Bacterial Agents↗

PubMed1996

[Nucleotide sequence and restriction fragment length polymorphism (RFLP) analysis of the long terminal repeat of human T-cell lymphotropic virus type II (HTLV-II)].

Molecular studies have demonstrated the existence of two major subtypes of human T-cell lymphotropic virus type II, HTLV-IIa and HTLV-IIb. In attempts to further classify this family of viruses we have carried out nucleotide sequence and restriction fragment length polymorphism (RFLP) analysis of the long terminal repeat (LTR), a region which has been shown in previous studies to have the greatest intra-and inter-subtype genomic divergence. Analysis of the nucleotide sequences suggested the existence of distinct phylogenetic groups in each subtype, and based on predicted differences in restriction endonuclease sites, RFLP analysis allowed the identification of four groups within the IIa subtype (a1-a4), and six within the IIb subtype (b1-b6). Nucleotide sequence analysis also suggested the possible existence of HTLV-II quasispecies. However this appeared not to be significant, and preliminary studies suggest that these would not be expected to appreciably influence the results of RFLP analysis. The validity of the RFLP method was demonstrated in an analysis of thirty-six randomly chosen samples from the blood donors from the New York City Blood Center where it could be shown that all could be successfully classified. Moreover, the RFLP analysis correctly matched the viruses in donors and recipients of contaminated blood in four situations where HTLV-II was inadvertently transmitted by transfusion. RFLP analysis of the LTR appears to be a rapid and reliable method to identify HTLV-II infection. This should prove useful in studies of the epidemiology and the characterization of viruses present both in non-indigenous in indigenous populations.

Base Sequence↗

PubMed2000

Independent introduction of transmissible F/D recombinant HIV-1 from Africa into Belgium and The Netherlands.

Most HIV-1 subtype F viruses described so far have been isolated from individuals originating in South America, Romania, or Central Africa. Previous studies have shown that subtype F viruses from these three areas can be distinguished by phylogenetic tree analysis of various parts of the HIV genome. Subtype F strains circulating in Central Africa and classified as subgroup F2 and F3 have relatively large nucleotide distances from strains of subgroup F1, which includes some African strains, along with strains from Romania and South America. Subtype F strains have now appeared in Europe. In this study, we analyzed the complete gag gene and a large fragment of the pol gene of seven strains of African origin that represent the three F subgroups. At least five of the seven strains appear to be intersubtype recombinants. Of four strains circulating in Belgium and the Netherlands, three were F/D mosaics and the fourth harboured a G(gag)/GH(pol)/F3(env) recombinant structure. Two of the three F/D mosaics showed identical breakpoints and were independently introduced in Belgium and the Netherlands. At least two of the mosaics were further transmitted. The remaining three strains of the seven we studied were isolated from individuals in Cameroon. Two included large or smaller F1 fragments in gag and pol. The third strain was subtype D along the entire gag and pol fragment. A parental African subtype F that showed no evidence for recombination was not found.

Africa↗

PubMed1996

HLA-A02 subtype distribution in Caucasians from northern Italy: identification of A0220.

This study describes a comprehensive easy to perform PCR-SSOP typing approach suitable for complete genomic subtyping of HLA-A*02. A single 1.6 kb PCR-amplificate spanning exons 2, 3 and 4 of the HLA-A*02 gene was used for hybridization with a panel of twenty-four SSOPs. This allowed unequivocal assignment of all so far known HLA-A2 subtypes, including A*0209 and A*0215N which differ for nucleotide substitutions in exon 4, without the need for two separate amplifications. Using this approach, HLA-A*02 subtype distribution was analyzed in 218 samples from unrelated, healthy individuals from northern Italy enrolled in the Italian Bone Marrow Registry and typed as HLA-A2 by serology or generic molecular analysis. As expected, A*0201 was found in the majority (92.6%) of samples. However, a significant number (6.8%) of individuals carried A*0205. Furthermore, A*0202, A*0208, A*0209 and A*0217, so far not described in Caucasians, were detected in a low number of samples (frequency ranging from 0.45% to 1.8%). Finally, a novel HLA-A*02 subtype, A*0220, was detected in 0.9% of the samples. As confirmed by DNA sequencing of exons 2 and 3, this allele is identical to A*0201 except for a single nucleotide substitution in codon 66 which changes the predicted amino acid sequence form Lys to Asn. The findings of this study have implications for the selection of HLA-A*02+ donors in unrelated bone marrow transplantation and of patients for specific immuno-therapy with HLA-A*02 restricted peptide vaccines.

Genes↗

PubMed2000

Elevated tumor necrosis factor-alpha activation of human immunodeficiency virus type 1 subtype C in Southern Africa is associated with an NF-kappaB enhancer gain-of-function.

The human immunodeficiency virus type 1 (HIV-1) epidemic within southern Africa is predominantly associated with the HIV-1C subtype. Functional analysis of the enhancer region within the long terminal repeat (LTR) indicates that HIV-1C isolates have >/=3 NF-kappaB binding sites, unlike other subtypes, which have only 1 or 2 sites. A correlation was shown between NF-kappaB enhancer configuration and responsiveness to the proinflammatory cytokine tumor necrosis factor (TNF)-alpha within the context of naturally occurring subtype LTRs, subtype-specific NF-kappaB enhancer regions cloned upstream of an isogenic HXB2 core promoter or a heterologous SV40 minimal promoter, and full-genome subtype clones. In all cases, TNF-alpha activation was correlated with the subtype configuration of the NF-kappaB enhancer. Whether the naturally occurring gain-of-function in the NF-kappaB enhancer of HIV-1C observed in this study can provide a selective advantage for the virus in vivo remains to be determined and warrants further study.

Binding Sites↗

PubMed1991

Restriction endonuclease patterns of herpes simplex virus DNA: subtyping of HSV-1 and HSV-2 strains from genital and nongenital lesions.

Herpes simplex type 1 (HSV-1) and type 2 (HSV-2) isolates from genital and nongenital infections were submitted to restriction endonuclease analysis for possible genomic changes in relation with the adaptation of the virus to a new site on the body. HSV-1 and HSV-2 strains were successfully divided into two subgroups using the Hin c II restriction enzyme. No correlation was found, however, between the proposed genomic subtypes H1A, H1B, H2A and H2B, and the genital or nongenital origin of the HSV strains.

Animals↗

PubMed2005

Isolation and characterization of visual pigment kinase-related genes in carp retina: polyphyly in GRK1 subtypes, GRK1A and 1B.

PURPOSE: Visual pigment is phosphorylated and inactivated after light stimulus. The responsible enzyme is known as rhodopsin kinase or G-protein-coupled receptor kinase 1 (GRK1) in rods. We recently showed that the kinase in cones (GRK7) has much higher activity than GRK1 in rods in carp retina. During the course of these studies, we realized that there are several subtypes of GRK1 and GRK7. In the present study, therefore, to identify the GRK1 and GRK7 subtypes expressed in carp photoreceptors, we determined their nucleotide sequences together with their expression patterns in carp retina. We also analyzed their relationships to other GRK1s and GRK7s phylogenetically. METHODS: Oligonucleotides corresponding to the amino acid sequences conserved in GRK1 or GRK7 were synthesized to screen the GRK subtypes in a carp retinal cDNA library. The isolated partial cDNAs were used to determine the full length of GRK subtypes. Genomic Southern hybridization was performed to learn whether each of the isolated GRKs is encoded by a single gene or it is an allelic variation. Tissue localization of the isolated GRKs was examined with in situ hybridization. RESULTS: A novel subtype of GRK1, GRK1B, was found in addition to the conventional GRK1 (called GRK1A subtype in this study) in carp retina. The GRK1A subtype, more specifically the GRK1A-1 subtype, which is related to the mammalian-type GRK1, was expressed in rods, while the GRK1B subtype, related to chicken GRK1, was expressed in cones. Since GRK7-1 was also expressed in cones, carp cones express both GRK7-1 and GRK1B. There were two paralogous genes in all of the GRK1 and GRK7 subtypes in carp retina: GRK1A-1a and 1A-1b, GRK1Ba and 1Bb, and GRK7-1a and 7-1b. Each of these genes was suggested to be encoded by a single gene in the carp genome, and each pair was found to be expressed in the same type of photoreceptors. CONCLUSIONS: Carp rods and cones express at least two kinds of visual pigment kinases. Phylogenetic analysis suggested that GRK7-1 together with GRK1A-1 and GRK1B appeared before divergence of vertebrates and that some of these genes were lost during evolution in a species-dependent manner. This evolutional process probably explains why the expression pattern of GRK1 and GRK7 is complex among vertebrate species.

Amino Acid Sequence↗

PubMed2006

High-resolution genomic profiles define distinct clinico-pathogenetic subgroups of multiple myeloma patients.

To identify genetic events underlying the genesis and progression of multiple myeloma (MM), we conducted a high-resolution analysis of recurrent copy number alterations (CNAs) and expression profiles in a collection of MM cell lines and outcome-annotated clinical specimens. Attesting to the molecular heterogeneity of MM, unsupervised classification using nonnegative matrix factorization (NMF) designed for array comparative genomic hybridization (aCGH) analysis uncovered distinct genomic subtypes. Additionally, we defined 87 discrete minimal common regions (MCRs) within recurrent and highly focal CNAs. Further integration with expression data generated a refined list of MM gene candidates residing within these MCRs, thereby providing a genomic framework for dissection of disease pathogenesis, improved clinical management, and initiation of targeted drug discovery for specific MM patients.

Chromosomes, Human↗

PubMed2003

In vitro detection of dissimilar amounts of hepatitis C virus (HCV) subtype-specific RNA genomes in mixes prepared from sera of persons infected with a single HCV genotype.

The level of in vitro detection of viral genomes in mixes with two different hepatitis C virus (HCV) subtypes was investigated by artificially mixing previously measured subtype-specific HCV RNA genomes. The RNAs in these mixtures were reverse transcribed and then PCR amplified by using two sets of primers corresponding to the 5' untranslated region and digested with endonucleases to analyze the restriction fragment length polymorphism patterns. This approach facilitated detection of a wider range of type-specific HCV genomes than originally described, beyond equimolar concentrations of contributing HCV subtypes. Moreover, by using computerized image analysis, this study also demonstrated that the true contribution of each virus type-and consequently of mixed infections-may be underestimated when only visual observation is carried out. These results may be useful for comparing data obtained from this and other currently used methodologies.

Genome, Viral↗

PubMed1991

Genomic structure of the human prototype strain H of hepatitis C virus: comparison with American and Japanese isolates.

Genomic RNA from the human prototype strain H of the hepatitis C virus (HCV-H) has been molecularly cloned and sequenced. The HCV-H sequence reported consists of 9416 nucleotides including the 5' and 3' untranslated regions. HCV-H shows 96% amino acid identity with the American isolate HCV-1 but only 84.9% with the Japanese isolates HCV-J and HCV-BK. In addition to the hypervariable region (region V) previously identified in the putative E2 domain, three other variable domains were identified: region V1 (putative E1), region V2 (putative E2), and region V3 (putative NS5). These regions appear rather conserved (86-100%) among the American isolates (HCV-1 and HC-J1) or among various Japanese isolates (HCV-J, HCV-BK, HCV-JH, and HC-J4) but show striking heterogeneity when the two subgroups are compared (42-87.5% amino acid difference). A structural similarity between the 5'-terminal hairpin structure of HCV and of poliovirus was observed. This study further suggests the existence of at least two genomic subtypes of HCV and confirms a distant relationship between HCV and pestiviruses.

Amino Acid Sequence↗

PubMed1992

Determination of the minimal length of preS1 epitope recognized by a monoclonal antibody which inhibits attachment of hepatitis B virus to hepatocytes.

The minimal amino acid sequence sufficient to be recognized efficiently by virus-attachment inhibiting murine monoclonal anti-preS1 antibody MA18/7 has been determined. We have constructed a recombinant gene library using the cloned coat protein gene of Escherichia coli RNA bacteriophage fr as a carrier. Different fragments of preS1 region from cloned hepatitis B virus (HBV) genomes, subtype ayw and adw, were inserted at position 2 of the 129 amino acid-long fr coat protein gene in the appropriate E. coli expression vectors. Fine mapping of preS1 epitope recognized by MA18/7 was accomplished by bidirectional shortening of the preS1 within original recombinant preS-fr coat protein genes with Bal31 exonuclease. Immunoblot analysis of the obtained recombinant protein library revealed that the tetrapeptide Asp-Pro-Ala-Phe (DPAF), located at the position preS(31-34) and conserved in all known HBV genomes, is sufficient to bind MA18/7 antibody. Recognition of the preS1 region by MA18/7 occurred irrespective of the amino acid context surrounding this DPAF tetrapeptide. Further shortening of this minimal epitope from the left or from the right side completely prevented antibody binding in immunoblots.

Amino Acid Sequence↗

PubMed2026

In vitro evaluation of sacituzumab govitecan in non-small cell lung cancer with actionable genomic alterations.

PURPOSE: The TROP2-directed antibody-drug conjugate sacituzumab govitecan (SG) has shown substantial therapeutic benefit in several malignancies; however, preclinical evidence supporting its activity in non-small cell lung cancer (NSCLC) is rare. MATERIALS AND METHODS: We evaluated 16 NSCLC cell lines harboring actionable genomic alterations for TROP2 expression and treated them with SG or its unconjugated payload, SN-38, for 3 days to determine cytotoxic effects. Apoptosis and DNA damage signaling were assessed using flow cytometry and western blot. SG internalization and lysosomal trafficking were visualized by confocal microscopy. RESULTS: SG had greater cytotoxic potency than SN-38, across all NSCLC cell lines, independent of genomic subtype or TROP2 expression level. Cell lines that were sensitive to SN-38 showed enhanced vulnerability to SG (P < 0.0001). Higher SLFN11 expression, a recognized determinant of SN-38 responsiveness, correlated with lower SG IC50 values. Both SG and SN-38 triggered apoptotic and DNA damage responses within 6-48 h, with SG inducing stronger activation of these pathways than SN-38. SG was efficiently taken up in CUTO17 and SNU-3173 adenocarcinoma cells, with more than 60% of the conjugate internalized within 3 h and subsequently localized to lysosomes. CONCLUSION: Our study provides in vitro evidence supporting the potential activity of SG in NSCLC with actionable genomic alterations. The efficacy of SG closely paralleled intrinsic sensitivity to the SN-38 payload, suggesting that DNA-damage responses, rather than oncogenic drivers, predominantly contribute to SG activity.

Actionable genomic alterations↗