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At least 181 records · Page 10Linked to original sources
PubMed2000

Near-full-length genome sequencing of divergent African HIV type 1 subtype F viruses leads to the identification of a new HIV type 1 subtype designated K.

We recently reported a high divergence among African subtype F strains. Three well-separated groups (F1, F2, and F3) have been shown based on the phylogenetic analysis of the p24 gag and envelope sequences with genetic distances similar to those observed for known subtypes. In this study, we characterized the near-full-length genomes of two strains from epidemiological unlinked individual belonging to each of the subgroups: F1 (96FR-MP411), F2 (95CM-MP255 and 95CM-MP257), and F3 (96CM-MP535 and 97ZR-EQTB11). Phylogenetic analysis of the near-full-length sequences and for each of the genes separately showed the same three groups, supported by high bootstrap values. Diversity plotting, BLAST subtyping, and bootstrap plotting confirmed that the divergent F strains correspond to nonrecombinant viruses. The divergence between F1 and F2 is consistently lower than that seen in any other intersubtype comparison, with the exception of subtypes B and D. Based on all the different analyses, we propose to divide subtype F into two subclades, with F1 gathering the known subtype F strains from Brazil and Finland, and our African strain (96FR-MP411), and F2 containing the 95CM-MP255 and 95CM-MP257 strains from Cameroon. The F3 strains, 97ZR-EQTB11 from the Democratic Republic of Congo and 96CM-MP535 from Cameroon, meet the criteria of a new subtype designated as K. The equidistance of subtype K to the other subtypes of HIV-1 suggests that this subtype existed as long as the others, the lower distance between B and D, and between F1 and F2 suggest a more recent subdivision for these latter strains.

Africa↗
PubMed1990

Synthetic oligopeptides bearing a common or subtypic determinant of hepatitis B surface antigen.

Two determinants of hepatitis B surface Ag (HBsAg), identified by mAb raised against polypeptide components, were characterized immunochemically. One was expressed on HBsAg irrespective of the four major subtypes, i.e., adw, adr, ayw, and ayr, whereas the other was subtypic but not identical to any of d, y, w, and r determinants. The common determinant was generated by a synthetic pentadecapeptide with a sequence of Thr-Thr-Ser-Thr-Gly-Pro-Cys-Lys-Thr-Cys-Thr-Ile-Pro-Ala-Gln representing amino acids 115-129 of the S gene product, and detected invariably in 366 HBsAg samples in sera from asymptomatic carriers in Japan. The activity of the S gene product, as well as the peptide (115-129), to bind with the mAb was not affected by alkylation alone, but was completely lost after reductive alkylation. The antigenic activity was lost when the S gene product was severed between Lys122 and Thr123 by trypsin. A microconformation maintained by the -Cys121-Cys124 bond, therefore, would be required for the common determinant. The other mAb identified an epitope of HBsAg that was mimicked by a synthetic tetradecapeptide with a sequence of Thr-Cys-Thr-Ile-Pro-Ala-Gln-Gly-Thr-Ser-Met-Phe-Pro-Ser, representing amino acids 123-136 of the S gene product. Among 16 HBsAg samples with known S gene sequences, 5 with Ile126 possessed this subtypic determinant, but the remaining 11 with Thr126 did not. The 5 hepatitis B virus genomes encoding the subtypic determinant differed less than 5.6% from each other in the entire nucleotide sequence, but by 8.0% or more from any of the other 11 genomes without the capacity to encode it.

Alkylation↗
PubMed2003

Classification and subtype prediction of adult soft tissue sarcoma by functional genomics.

Adult soft tissue sarcomas are a heterogeneous group of tumors, including well-described subtypes by histological and genotypic criteria, and pleomorphic tumors typically characterized by non-recurrent genetic aberrations and karyotypic heterogeneity. The latter pose a diagnostic challenge, even to experienced pathologists. We proposed that gene expression profiling in soft tissue sarcoma would identify a genomic-based classification scheme that is useful in diagnosis. RNA samples from 51 pathologically confirmed cases, representing nine different histological subtypes of adult soft tissue sarcoma, were examined using the Affymetrix U95A GeneChip. Statistical tests were performed on experimental groups identified by cluster analysis, to find discriminating genes that could subsequently be applied in a support vector machine algorithm. Synovial sarcomas, round-cell/myxoid liposarcomas, clear-cell sarcomas and gastrointestinal stromal tumors displayed remarkably distinct and homogenous gene expression profiles. Pleomorphic tumors were heterogeneous. Notably, a subset of malignant fibrous histiocytomas, a controversialhistological subtype, was identified as a distinct genomic group. The support vector machine algorithm supported a genomic basis for diagnosis, with both high sensitivity and specificity. In conclusion, we showed gene expression profiling to be useful in classification and diagnosis, providing insights into pathogenesis and pointing to potential new therapeutic targets of soft tissue sarcoma.

Adult↗
PubMed2001

A new human immunodeficiency virus type 1 circulating recombinant form from Tanzania.

It is becoming increasingly important to identify and to study human immunodeficiency virus type 1 (HIV-1) circulating recombinant forms (CRFs) with evidence of epidemic spread, since mosaic strains arise frequently, especially in populations where multiple subtypes cocirculate. We describe the almost complete nucleotide sequence of 3 subtype C and D recombinant viruses, selected from a pool of 13 D(gag)-D/C/D(env) perinatally infected infants from Dar es Salaam, Tanzania. All three genomes had cross-over points with approximately the same genomic localization. The subtype C-like sequences were located within pol, vif, vpr, vpu, the first exons of rev and tat, V3, and the U3-R regions of the LTR. Phylogenetic analyses of the full-length genomic sequences from these viruses showed the formation of a distinct subcluster on the HIV-1 subtype D branch. The pattern of recombination of genomes belonging to this new CRF, named CRF10_CD, might have resulted from independent recombination events occurring at high frequency or from a single source that originated earlier in this population. Future surveys will be needed to determine the potential of this CRF for epidemic spread.

Consensus Sequence↗
PubMed2005

Genetic diversification and recombination of HIV type 1 group M in Kinshasa, Democratic Republic of Congo.

As the HIV-1 pandemic becomes increasingly complex, the genetic characterization of HIV strains bears important implications for vaccine research. To better understand the molecular evolution of HIV-1 viral diversity, we performed a comparative molecular analysis of HIV strains collected from high-risk persons in Kinshasa, Democratic Republic of Congo (DRC). Analysis of the gag-p24, env-C2V3 and -gp41 regions from 83 specimens collected in 1999-2000 revealed that 44 (53%) had concordant subtypes in the three regions (14 subsubtype A1, 10 subtype G, 8 subtype D, 5 subtype C, 2 each subsubtype F1 and CRF01_AE, and one each of subtypes H and J, and subsubtype A2, while the remaining 39 (47%) had mosaic genomes comprising multiple subtype combinations. Similar multisubtype patterns were also observed in 24 specimens collected in 1985. Sequence analysis of the gag-pol region (2.1 kb) from 21 discordant specimens in the gag-p24, env-C2V3 and -gp41 regions in 1985 and 1999-2000 further confirmed the complex recombinant patterns. Despite the remarkable similarity in overall subtype distribution, the intra- and intersubtype distances of major subtypes A1 and G increased significantly from 1985 to 1999-2000 (p=0.018 and p=0.0016, respectively). Given the complexity of HIV-1 viruses circulating in DRC, efforts should focus on the development of vaccines that result in cross-clade immunity.

Democratic Republic of the Congo↗
PubMed2006

Peroxisome proliferator-activated receptor subtype- and cell-type-specific activation of genomic target genes upon adenoviral transgene delivery.

Investigations of the molecular events involved in activation of genomic target genes by peroxisome proliferator-activated receptors (PPARs) have been hampered by the inability to establish a clean on/off state of the receptor in living cells. Here we show that the combination of adenoviral delivery and chromatin immunoprecipitation (ChIP) is ideal for dissecting these mechanisms. Adenoviral delivery of PPARs leads to a rapid and synchronous expression of the PPAR subtypes, establishment of transcriptional active complexes at genomic loci, and immediate activation of even silent target genes. We demonstrate that PPARgamma2 possesses considerable ligand-dependent as well as independent transactivation potential and that agonists increase the occupancy of PPARgamma2/retinoid X receptor at PPAR response elements. Intriguingly, by direct comparison of the PPARs (alpha, gamma, and beta/delta), we show that the subtypes have very different abilities to gain access to target sites and that in general the genomic occupancy correlates with the ability to activate the corresponding target gene. In addition, the specificity and potency of activation by PPAR subtypes are highly dependent on the cell type. Thus, PPAR subtype-specific activation of genomic target genes involves an intricate interplay between the properties of the subtype- and cell-type-specific settings at the individual target loci.

Adenoviridae↗
PubMed1995

Sporadic activation of Epstein-Barr virus in thyroid lymphoma.

The causal role of Epstein-Barr virus (EBV) in the development of B-cell lymphoma, especially in immunocompromised individuals, has been suggested. The purpose of the present study was to evaluate an association of EBV with thyroid lymphoma (TL) and chronic lymphocytic thyroiditis (CLTH) which is known to play an important role in the development of TL. Thirty cases with TL and 28 with CLTH were studied for presence or absence of EBV genome in the lesions using the polymerase chain reaction (PCR) and the in situ hybridization method. EBV genomes were detected by PCR in one and two cases with CLTH and TL, respectively. Subtyping of EBV genome was possible in one TL case showing B-type in EBNA-2 coding region. In situ hybridization revealed positive signals in the nucleus of lymphoma cells, which also expressed latent membrane protein-1. The present findings indicate that activation of EBV in TL is not common.

Adolescent↗
PubMed2005

Phylogeny of African complete genomes reveals a West African genotype A subtype of hepatitis B virus and relatedness between Somali and Asian A1 sequences.

Hepatitis B virus (HBV) is a major cause worldwide of liver disease, including hepatocellular carcinoma. There are eight known genotypes (A-H), of which genotype A has been divided into two subtypes: A2, prevalent in Europe, and A1, which is prevalent in sub-Saharan Africa, but also occurs in southern Asia. In this study, which includes 14 new complete genomes of non-European genotype A HBV, it was found that West African strains seem to constitute a new subgroup, A3. The high degree of genetic diversity within Africa indicates that genotype A originates from Africa. Based on a 2 % genetic distance between Asian and Somali sequences, it seems that the A1 subtype has spread from East Africa to southern Asia during the last 1000-2000 years. Moreover, it is proposed here that the A2 subtype originates from southern Africa and was imported to Europe around 500 years ago or later. The finding of T-1809/1812 close to the precore start codon and T-1862 and A-1888 in the precore region in HBV e antigen-positive children with signs of a mimimal immune response indicates that these substitutions are stable variants, rather than mutations emerging during infection in individual carriers.

Adolescent↗
PubMed1995

The presence and subtype of Epstein-Barr virus in B and T cell lymphomas of the sino-nasal region from the Osaka and Okinawa districts of Japan.

BACKGROUND: Association between Epstein-Barr virus (EBV) and human malignancies, including sino-nasal lymphoma (SNL), has been suggested. EBV-associated malignancies have been reported to show distinct geographic distribution. EXPERIMENTAL DESIGN: In the present study, the presence of an EBV genome and its subtypes (type A and B) were examined in 52 cases of sino-nasal lymphomas of B and T cell type collected from two areas of Japan: Osaka, situated on the mainland, and Okinawa, islands situated in a southwest part of Japan with a subtropical climate. Our previous epidemiologic study showed that the frequency of nasal T cell lymphoma was 3.5 times higher in Okinawa than in Osaka. RESULTS: There were no prominent differences in age distribution or sex ratio between these two areas: age ranged 8 to 85 (median 54) years, with a male to female ratio of 1.26:1. Immunophenotypically, 27 cases were B cell type (20 Osaka, 7 Okinawa), 20 were T cell type (9 Osaka, 11 Okinawa), and 5 were undefined. By PCR, EBV positivity in throat washings of normal individuals in Osaka and Okinawa was 52 and 53%, respectively, with marked preponderance of subtype A in both areas. EBV genome was found in 6 of 15 cases (40%) and 4 of 5 cases (80%) of nasal B and T cell lymphomas in Osaka and in 3 of 7 cases (43%) and 7 of 7 cases (100%) in Okinawa, showing the different frequencies of positivity by immunophenotype but not by district. All but one patient had type A EBV. The in situ hybridization confirmed the results of PCR as positive signals in the nucleus of proliferating cells. Latent membrane protein-1 was expressed in 13 of 22 cases (59%). CONCLUSIONS: These findings suggest that EBV, exclusively type A, might be a causative factor in sino-nasal lymphoma of not only T cell but also B cell type in Japan.

Adolescent↗
PubMed2002

Forty-one near full-length HIV-1 sequences from Kenya reveal an epidemic of subtype A and A-containing recombinants.

OBJECTIVE: To further define the genetic diversity of HIV-1 in Kenya using approaches that clearly distinguish subtypes from inter-subtype recombinants. DESIGN: Near full genome sequencing and analysis were used, including sensitive new tools for detection and mapping of recombinants. METHODS: Purified peripheral blood mononuclear cell DNA from 41 HIV-1 positive blood donations collected from six hospitals across southern Kenya was used to amplify near full-length genomes by nested PCR. These were sequenced on an ABI 3100 automated sequencer and analyzed phylogenetically. RESULTS: Among 41 near full-length genomes, 25 were non-recombinant (61%) and 16 were recombinant (39%). Of the 25 pure subtypes, 23 were subtype A, one was subtype C and one was subtype D. Most recombinants consisted of subtype A and either subtype C or subtype D; a few contained A2, a recently identified sub-subtype. Two A2/D recombinants had identical breakpoints and may represent a circulating recombinant form. A third A2/D recombinant had the same structure as a previously described Korean isolate, and these may constitute a second A2-containing circulating recombinant form. CONCLUSIONS: In Kenya, 93% of HIV-1 genomes were subtype A or A-containing recombinant strains. Almost 40% of all strains were recombinant. Vaccine candidates tested in Kenya should be based on subtype A strains, but the methods used for evaluation of breakthrough infections during future vaccine trials should be capable of identifying non-A subtypes, the A2 sub-subtype, and recombinants.

Disease Outbreaks↗
PubMed2006

Amplification of the entire genome of influenza A virus H1N1 and H3N2 subtypes by reverse-transcription polymerase chain reaction.

This study describes the development of a simple RT-PCR method to amplify the whole genome of the influenza A virus based on the amplification of full-length gene segments. Primers were designed based on the conserved regions of both the 5'-end and the 3'-end of each gene segment. After optimizing the duration and temperature of denaturing, annealing, and extension, these primers could amplify all of the full-length gene segments. To test the accuracy of the method, all amplicons were subjected to DNA sequencing with an autosequencer. Eighteen strains of influenza A virus which belonged to H1N1 or H3N2 subtypes were tested. All eight segments of both subtypes were successfully amplified in all tested strains. Using a newly developed reverse-transcriptase (RT), primers and PCR running conditions, this study established a protocol to amplify the entire genome of the influenza A virus. This method provides a tool which can be used for the amplification of all genes of the H1N1 and H3N2 subtypes of influenza A virus prior to analysis of their sequences, and to construct expression plasmids for further study.

DNA Primers↗
PubMed2026

Hierarchical modeling of tumor subtypes in cell lines using large-scale genomic datasets.

Cancer cell lines (CLs) are widely used to study tumor biology and drug response, yet their translational relevance is often limited by inaccurate subtype annotations. Existing CL-tumor matching approaches are frequently constrained by flat classification schemes, weak subtype definitions, and the exclusion of normal tissue references, leading to potential confounding of tumor-specific and tissue-of-origin signals. To address these limitations, a hierarchical classification (HC) framework is presented in which CLs are aligned with patient tumors across biological resolutions, from organ to molecular subtype. Gene expression profiles from 802 CLs, 5,612 tumors from The Cancer Genome Atlas (TCGA) , and 8,939 non-cancerous tissues were integrated to separate oncogenic signals from tissue-specific signals. Node-specific features were selected using maximum relevance minimum redundancy, and balanced accuracies of 89% in cross-validation and 75%, and 80% on external datasets were achieved. Through the framework, 43 CLs were reassigned, and clinically relevant underrepresented subtypes were identified.

cancer cell lines↗
PubMed2005

Substitutions in the reverse transcriptase and protease genes of HIV-1 subtype B in untreated individuals and patients treated with antiretroviral drugs.

The nucleotide transition G-->A is known as a hypermutation due to its high prevalence in HIV-1 and other pathogens. However, the contribution of the G-->A transition in the generation of drug resistance mutations is unknown . Our objective was to ascertain the rate of nucleotide substitutions in protease (PR) and reverse transcriptase (RT) in both untreated and treated HIV-1 patients. Genotypic analysis was performed on viruses from both treated and untreated patients with subtype B infections. Nucleotide genomic diversity was compared with a consensus subtype B reference virus. Then, the prevalence of resistance-associated mutations in different subgroups of treated patients was evaluated in relation to the patterns of nucleotide transitions. In untreated patients (n = 50) G-->A was most prevalent, followed by A-->G, C-->T, and T-->C transitions. In treated patients (n = 51), the prevalence of A-->G was similar to that of G-->A. Among mutations that confer resistance to antiretroviral drugs, M184V was present in 76% of treated patients and K70R in 31% (A-->G transitions). Other frequent mutations in RT included T215Y (C-->A and A-->T substitutions), which was prevalent in 31% of treated patients. In PR, a L90M (T-->A substitution) was prevalent in 47% of protease inhibitor (PI)-treated patients. In conclusion, the G-->A transition was most prevalent in RT and PR among untreated patients. In contrast, A-->G was the most prevalent transition in patients treated with antiretroviral drugs.

Adenine↗
PubMed1997

Molecular subtyping of human T-lymphotropic virus type I (HTLV-I) by a nested polymerase chain reaction-restriction fragment length polymorphism analysis of the envelope gene: two distinct lineages of HTLV-I in Taiwan.

The major type of human T-lymphotropic virus type I (HTLV-I), generally referred to as the cosmopolitan type, has been grouped into three subtypes (A, B, and C) by phylogenetic analysis of the long terminal repeat sequences of the viral genome. Twelve subtype-specific nucleotide variations have been deduced by comparison between the envelope (env) sequences of 16 HTLV-I strains with defined subtypes and 9 Taiwanese HTLV-I strains. To gain further insights into the molecular epidemiology of HTLV-I and the origin of this virus in Taiwan, a rapid method of identification for the cosmopolitan subtypes was developed by using a nested polymerase chain reaction (PCR) and subsequent restriction fragment length polymorphism (RFLP) studies using the two subtype B-specific and four subtype C-specific nucleotides located within the positions 5708 to 6320 of the envgene. The nested PCR-RFLP method was used to subtype HTLV-I from four virus-positive cell lines derived from 1 Japanese and 3 North American patients, as well as 41 blood-unrelated Taiwan Chinese. The sequences of PCR products were determined and the six positions of subtype-specific nucleotide variations were examined. The sequence data completely supported the subtyping data via the nested PCR-RFLP method. The results demonstrated that, as is the case in Japan, at least two distinct cosmopolitan subtypes (A and B) of HTLV-I were present in Taiwan, but the more prevalent subtype in Taiwan is A in contrast to subtype B in Japan. Furthermore, rapid subtyping could facilitate molecular epidemiological studies of HTLV-I infection and linkage between HTLV-I subtypes and virus-associated diseases.

Base Sequence↗
PubMed2003

A cluster of HIV type 1 subtype C sequences from Ethiopia, observed in full genome analysis, is not sustained in subgenomic regions.

The impact of HIV-1 genetic diversity on candidate vaccines is uncertain. One approach to minimize genetic diversity in the evaluation of HIV-1 vaccines is to match the vaccine sequence to the predominant subtype in a vaccine cohort. Over two million Ethiopians are infected with HIV-1, and the predominant subtype is thought to be subtype C. Understanding the phylogenetic relationships between sequences from Ethiopia and within subtype C can help decide what sequence(s) should comprise a candidate vaccine. To that end, nearly full genome sequencing was used to characterize HIV-1 from volunteers who emigrated from Ethiopia. DNA extracted from peripheral blood mononuclear cells (PMBC) was amplified using primers in the long terminal repeats to generate nearly full-length genomes. Amplicons were directly sequenced with dye terminators and automated sequencers. Sequences were phylogenetically analyzed by neighbor joining. The six new Ethiopian sequences were all subtype C, consistent with previous partial and full genome analysis. Together with two other Ethiopian sequences, the new sequences formed a geographic cluster when the complete genome was analyzed. However, subgenomic trees showed only a weak geographic cluster, or none, with respect to Ethiopian strains. Although immunological responses must be considered, from a phylogenetic perspective, there is no compelling support for use of Ethiopian subtype C sequences, compared to other subtype C, as vaccine prototype strains.

Base Sequence↗
PubMed1996

Alignment of receptor nomenclature with the human genome: classification of 5-HT1B and 5-HT1D receptor subtypes.

The continuing rapid progress towards a complete database of structural information on the human genome creates a challenge of ensuring that current schemes for classifying and naming receptors and ion channels effectively integrate this information with functional data to provide unambiguous principles for classification. In this article, Paul Hartig and colleagues review the recent deliberations of the Serotonin Club Nomenclature Committee and outline a number of its recommendations aimed at encouraging consistency in current and future receptor nomenclature. Based on these principles, the present classification of 5-HT1B and 5-HT1D receptors is reconsidered, and a revised nomenclature for 5-HT1B, 5-HT1D alpha and 5-HT1D beta receptor subtypes is suggested.

Animals↗
PubMed2004

Molecular determinants of antigenicity of two subtypes of the tick-borne flavivirus Omsk haemorrhagic fever virus.

In 1964, D. H. Clarke defined two antigenic subtypes of Omsk haemorrhagic fever virus (OHFV) based on polyclonal antibody absorption and haemagglutination assays. The current report defines the molecular basis for these antigenic subtypes by comparison of the complete genomes of OHFV strains Kubrin (subtype I) and Bogoluvovska (subtype II). There were six nucleotide differences between these two strains throughout the entire genome and they encoded four amino acid changes including three in the viral envelope (E) protein. Two of these changes were in solvent-exposed regions of domain 3 of the E protein, one of which lies in a region that could easily function in virus-host cell or virus-antibody interactions. These results demonstrate the minimal changes that are required to significantly alter the antigenicity of flaviviruses and also demonstrate the tremendous genetic stability of the tick-borne flaviviruses.

Amino Acid Sequence↗