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At least 1,279 records · Page 71Linked to original sources
PubMed2004

gp120 sequences from HIV type 1 subtype C early seroconverters in India.

A limited number of full-length gp120 sequences are currently available for subtype C HIV-1 from India. Sequence data from HIV-1 subtype C in early seroconverter stage virus are also very limited. With the objective of identifying the sequence variation in early seroconverters, we compared Indian subtype C gp120 sequences obtained from six early seroconverters presented in this study with non-Indian subtype C sequences from other parts of the world obtained from the Los Alamos database and subtype C potential vaccine candidate sequences. All these samples were collected within a few weeks of seroconversion and hence they represent gp120 sequences of currently circulating viral strains in India. The phylogenetic tree indicated that the Indian sequences compared here clustered together within the C clade. The seroconverter sequences presented in the study would surely help in identifying the immunogenic epitopes and could be utilized further for developing effective prophylactic strategies against HIV-1 subtype C for India.

Amino Acid Sequence↗
PubMed1999

An infectious DNA clone of HIV type 1 subtype C.

Among the 10 subtypes of the M group of human immunodeficiency virus type 1, subtype C is the most prevalent in India and may dominate worldwide in the near future; however, there has been no report on the infectious DNA clone of this subtype. We have isolated an infectious DNA clone of the 93IN101 strain of HIV-1 subtype C, which was isolated in India in 1993. MAGIC5 cells, which are derived from HeLa-CD4-LTR-beta-gal (MAGI) cells and express CCR5, were inoculated with the 93IN101 strain of HIV-1 subtype C. The genomic DNA of the infected cells was used as a template for amplification of the HIV-1 genome. The genome DNA obtained was subcloned into pBR322, and the resulting plasmid was designated as pIndie-C1. The insert of pIndie-C1 was 9680 bp in length and had an intact genomic organization with open reading frames of all structural, regulatory, and accessory proteins. Phylogenetic analysis confirmed that the nucleotide sequence of pIndie-C1 is closely related to those of HIV-1 subtype C isolated in India. Transfection of pIndie-C1 into 293T cells yielded as much virus as did pNL432, one of the most widely used HIV DNA clones. The recovered Indie-C1 virus infected MAGIC5 but not the parent MAGI cells, indicating that Indie-C1 is CCR5 tropic. Expressed Env protein was reacted efficiently with the sera of HIV-1-infected patients of India, but not of Japan. Expression of Nef and Vpr was also confirmed by immunoblotting.

Gene Products, env↗
PubMed1999

Genetic similarity of HIV type 1 subtype E in a recent outbreak among injecting drug users in northern Vietnam to strains in Guangxi Province of southern China.

To investigate the molecular epidemiology of a recent HIV-1 outbreak in northern Vietnam and its relation to the epidemic in surrounding areas, we analyzed 17 HIV-positive blood specimens from 3 heterosexuals, 2 sexually transmitted disease patients, and 12 injecting drug users (IDUs), collected in 4 provinces near Hanoi in 1998. These were compared with the specimens from Ho Chi Minh City (n = 10) and An Giang Province (n = 10) in southern Vietnam and with published sequences from neighboring countries. Genetic subtyping based on the env C2/V3 sequences revealed that HIV-1 subtype E predominated throughout Vietnam in all risk populations; the exception was one typical United States-European-type HIV-1 subtype B detected in a patient in Ho Chi Minh City, the first case of HIV infection identified in Vietnam in 1990. The HIV-1 subtype E sequences identified in 9 of the 12 IDUs from northern provinces were closely related phylogenetically to those in IDUs in nearby Guangxi Province of China, and also shared a common amino acid signature downstream of the env V3 loop region. The low interperson nucleotide diversity among IDUs in northern Vietnam supports the view that HIV-1 subtype E was introduced recently among IDUs in northern Vietnam. These data indicate a linkage between HIV-1 circulating among IDUs in northern Vietnam and southern China, and suggest recent transborder introductions as the likely source of HIV-1 subtype E in northern Vietnam.

Adolescent↗
PubMed1999

Phenotypic characteristics of human immunodeficiency virus type 1 subtype C isolates of Ethiopian AIDS patients.

It has been estimated that, to date, about 48% of all HIV-infected people in the world carry HIV-1 subtype C virus. Therefore, it is of great importance to gain better knowledge about the genetic and biological characteristics of this virus subtype. In the present study, the biological properties of HIV-1 isolates obtained from nine Ethiopian patients with AIDS were studied. DNA sequencing of the V3 loop of gp120 classified the isolates as subtype C. In primary isolation cultures, virus infection was accompanied by syncytium formation and cell lysis. Interestingly, when examining the growth in primary monocyte-macrophage cultures, initial low-level virus replication was followed by a nonproductive state, from which virus could be rescued by cocultivation with Jurkat(tat) cells. Furthermore, none of the isolates replicated in T cell lines (CEM, MT-2, HuT-78, and H9) or in the promonocytic cell line U937 clone 2. All isolates could use CCR5 as coreceptor, whereas no isolates could use CCR2b, CCR3, CCR5, CXCR4, Bonzo/STRL33, or BOB/GPR15. The genotype of the V3 region correlated with the MT-2 negative/non-syncytium-inducing (NSI) phenotype. Comparative studies revealed that the scarcity of CXCR4 usage as well as other phenotypic characteristics of subtype C isolates distinguish this subtype. On the basis of these data, we suggest that in addition, factors other than viral phenotype may govern the pathogenic potential of subtype C isolates.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Genetic heterogeneity of HIV type 1 subtypes in Kimpese, rural Democratic Republic of Congo.

A relatively low and stable seroprevalence of HIV-1 was previously reported among pregnant women attending for antenatal care between 1988 and 1993 in Kimpese, a rural town in the Democratic Republic of Congo (DRC, formerly Zaire). To characterize the HIV-1 subtypes circulating in this area, we have examined a 330-bp fragment of the p17 region of the gag gene of HIV-1 strains obtained from 70 patients (55 mothers, 15 children), of whom 61 were epidemiologically unlinked. Phylogenetic analyses revealed the existence of at least seven HIV-1 subtypes within the Kimpese region. Among the 61 epidemiologically unlinked patients, subtype A was predominant and found in 29 (47.5%) individuals. Other subtypes cocirculating in this rural part of DRC include subtypes C (1.6%), D (9.8%), F (3.2%), G (6.5%), H (21.3%), and J (4.9%). Sequences from four patients did not cluster with any of the currently documented HIV-1 subtypes, in analyses of fragments of both the gag (247 to 330 bp, 197 bp, and 310 bp) and env (340 bp) genes. Overall, comparisons of the gag(p17) gene regions revealed high pairwise divergences (mean, 19.9%; range, 1 to 46%). This level of gag(p17) gene variation in the DRC is considerably greater than previously appreciated. These results are relevant for the molecular epidemiology of HIV-1 in Africa and for the design of a future vaccine against HIV-1 in this region.

Adolescent↗
PubMed2002

Differential response to stem cell factor and Flt3 ligand by the FAB subtype in acute myeloid leukemia clonogenic cells.

Proliferative response of blast clonogenic cells to various hematopoietic growth factors (HGF), including stem cell factor (SCF) and flt3 ligand (FL) was investigated in 100 patients with acute myeloid leukemia (AML) and chronic myelogenous leukemia (CML) in myeloid crisis (MC). The frequency of spontaneous colony formation was significantly high in CML in MC (55%) and AML French-American-British (FAB) subtype M4 (48%) compared with M2 (16%). No spontaneous colony was formed in any of the patients with M1 and M3. The frequency of proliferative response to various HGF alone and in combination according to FAB subtype and CML in MC was as follows: that to granulocyte colony-stimulating factor (G-CSF) was lowest in M1 and CML in MC (50%) compared with other FAB subtypes (>or=86%), that to granulocyte-macrophage CSF (GM-CSF) was lowest in CML in MC (44%) compared with FAB subtypes (>or=74%), and that to interleukin-3 (IL-3) was lowest in CML in MC (30%) compared with FAB subtypes (>or=78%). SCF and FL stimulated blast colony formation in 11% and 17% of patients with M3, respectively, but there was no response to both, and in 60% and 57% of patients with CML in MC, respectively, with 14% showing a response to both. The frequency of proliferative response to both SCF and FL increased in the order of M1 (33%), M2 (63%), M4-5 (95%), and M6 (100%). The results are summarized as follows: absence of spontaneous colony formation and response to HGF other than SCF and FL, designated as HGF-dependent growth (M3); spontaneous colony formation and lowest response to HGF, designated as autonomous growth (CML in MC); and spontaneous colony formation and highest response to HGF including SCF and FL, designated as autocrine growth (M4-6). M1 and M2 were intermediate between CML in MC and M4-6. The relation between in vitro growth pattern of blast clonogenic cells and prognosis in AML FAB subtype and CML in MC is discussed.

Acute Disease↗
PubMed2004

Potential drug resistance polymorphisms in the integrase gene of HIV type 1 subtype A.

Variation in HIV-1 genes within and between subtypes has been best defined in the env gene, however, other more conserved genes vary between subtypes. Integrase (IN) and other regions of the pol gene are highly conserved due to their integral role in HIV replication and therefore are targets for antiviral drugs. In this study 3 individuals, infected heterosexually with HIV-1 subtype A, were examined for IN polymorphisms. Two patients' sequences clustered phylogenetically with other subtype A sequences and one patient's sequence was most similar to the circulating recombinant form CRF_02. No polymorphisms were observed in either of the motifs containing residues critical residues for IN activity. Polymorphisms were observed in a residue associated with resistance to anti-integrase drugs. In addition, a number of unique polymorphisms were observed in one individual (WM1666). IN can vary significantly within a subtype as well as between subtypes, and mutations associated with resistance to anti-integrase compounds can be present in drug naive individuals.

Amino Acid Sequence↗
PubMed2004

Documentation of subtype C HIV Type 1 strains in Argentina, Paraguay, and Uruguay.

HIV subtypes B, F, and BF recombinants have been previously reported in South America. This report describes the presence of HIV-1 subtype C infection in the countries of Argentina, Uruguay, and Paraguay dating back to at least 1999. Surveillance for uncommon non-B/non-F subtype viruses circulating in South America has been conducted in samples obtained from nine countries. Peripheral blood mononuclear cells (PBMC), dried filter paper (FP), and fresh blood (FB) samples were collected from HIV-positive patients from Ecuador, Colombia, Venezuela, Peru, Chile, Bolivia, Argentina, Uruguay, and Paraguay. From a total of 2962 HIV seropositive samples examined during a 9-year period (1995-2003), only 11 (0.4%) were found to be infected with non-B/non-F HIV variants. Eight of these 11 strains were determined to be subtype C by heteroduplex mobility assay (HMA). Five of these 8 strains were further characterized by sequencing and phylogenetic analysis of the protease (Pro) and reverse transcriptase (RT) region of the genome and two were sequenced full length. One of the strains was found to be a unique BC recombinant. The spread of a third subtype of HIV, subtype C, should raise the question of its potential future role in the HIV epidemic in this region.

Adult↗
PubMed2005

Nigerian HIV type 2 subtype A and B from heterotypic HIV type 1 and HIV type 2 or monotypic HIV type 2 infections.

The presence of HIV-2 in Nigeria has been confirmed serologically, but not genetically. To determine the frequency of HIV-2 infections and the dynamics between HIV-1 and HIV-2 in 35 of 36 Nigerian states, 420 blood samples were collected in 1999. Antibodies to HIV-1 and HIV-2 were detected by EIA and seroreactivity was confirmed with the INNO-LIA HIV Line Assay. The frequency of HIV-2 was 4.3% (18 of 420), with 3.8% (16 of 420) HIV-1 and HIV-2 (HIV-1/2) heterotypic and 0.5% (2 of 420) HIV-2 homotypic infections. The presence of HIV-2 subtype B in the two monotypic HIV-2 infections and subtype A in 11 (68.8%) of 16 HIV-1/2 dually seropositive samples was established by sequencing and phylogenetic analysis. HIV-2 subtype B viruses were not found in any of the HIV-1/2 dual infections, and HIV-2 subtype A strains were not identified in either of the two monotypic HIV-2 infections. Since our sample size was small and represented only convenience samples, larger randomized studies will be needed to better understand the dynamics of infection between HIV-1 and different HIV-2 subtypes and to determine whether significant biological differences exist among the HIV- 2 subtypes.

DNA, Viral↗
PubMed2005

Impact of HIV type 1 genetic subtype on the outcome of antiretroviral therapy.

The objective of this study was to investigate the short-term virological outcome of antiretroviral combination therapy (ART) in relation to infection with different HIV-1 genetic subtypes. Antiretroviral drug-naive patients in Sweden were prospectively enrolled and followed for 6 months when starting ART in the period from January 1998 to January 2002. Plasma-HIV-1 RNA levels, CD4 counts, and type of ART regimen were recorded. The HIV-1 subtype was determined by direct sequencing of regions of the env or pol genes. Data from 172 patients who harbored subtypes A, B, C, D, G, and CRF01_AE were analyzed (32 A, 44 B, 34 C, 18 D, 5 G, and 19 CRF01_AE). Of all patients 84% had undetectable plasma HIV-1 RNA levels after 6 months of ART. Patients infected with CRF01_AE more often had undetectable HIV-1 RNA plasma levels than patients infected with subtypes A or D. However, the possibility that this difference is due to ethnicity cannot be ruled out. Of patients of African origin, 77% had undetectable viral load after 6 months of treatment, while the corresponding figures for Caucasians and Asians were 91% and 100%, respectively. Thus, we have found an overall good short-term virological outcome after the initiation of ART in a cohort of ARV-naive patients of diverse ethnic background infected with different HIV-1 genetic subtypes. In univariate analysis ethnicity, but not genetic subtype, correlated with virological response. However, the impact of ethnicity was moderate. Patients of African origin, who had the poorest outcome, showed a 77% virological response rate.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Genetic analysis of regulatory, promoter, and TAR regions of LTR sequences belonging to HIV type 1 Non-B subtypes.

Transcriptional activation of HIV-1 gene expression is controlled by the interaction of sequence-specific transcription factors with the long terminal repeat (LTR). Information about differences between LTR regions in distinct HIV-1 subtypes is scarce. LTR sequences, including regulatory, enhancer, promoter, and TAR regions, were genetically characterized and compared in 59 HIV-1-infected individuals known to be infected with non-B subtypes. Phylogenetic analyses ascribed the LTR regions to the following subtypes: 10A, 2B, 6C, 1D, 2E, 2F, 16G, 3J, 2H, and 2U. Up to 34% of the samples were LTR/PR recombinants. The LTR region revealed a high degree of genetic variability among distinct HIV-1 subtypes and showed several subtype-specific markers, which hypothetically could influence the interactions with cellular transcription factors, leading to different transcriptional levels among distinct HIV-1 clades. To our knowledge, this is the first characterization of LTR sequences belonging to subtypes J and H.

Adult↗
PubMed2006

Full-length genome analysis of human immunodeficiency virus type 1 subtype C in Brazil.

The most prevalent HIV-1 clade in the global epidemics is C, and this clade is also becoming important in the Brazilian epidemics. In this study, we characterized HIV-1 subtype C variants by sequencing their near full-length genomes. DNA was extracted from six samples previously classified in our laboratory as subtype C on the basis of partial genome sequencing. Amplification was carried out by overlapping PCR followed by direct sequencing. Phylogenetic analysis of full length genomes confirmed that all isolates belonged to subtype C, which formed a highly supported monophyletic cluster and showed a nucleotide distance of 5.4%. The core promoter of all isolates contained three NF-kappaB binding motifs. Our results suggest that subtype C viruses circulating in Brazil were likely introduced recently from a unique point source. The independent clustering of Brazilian subtype C on the phylogenetic tree suggests the profile of an ideal local candidate for the development of a single subtype vaccine.

Brazil↗
PubMed2006

First case of HIV Type 1 subtype F among men who have sex with men in Colombia.

To study the molecular epidemiology of human immunodeficiency virus (HIV) strains among men who have sex with men (MSM), the main high-risk group for HIV infection in Colombia, 113 HIV-positive MSM subjects recruited in Bogotá during the year 2002 were genotyped. By heteroduplex mobility assay (env HMA) all samples were classified as subtype B. Partial sequencing of the protease and the reverse transcriptase (Pro/RT) regions performed on a random subset of 10 samples revealed that nine were classified as subtype B, and one sample was subtype F. The specimen that is subtype F in pol and subtype B in env is likely to be is either a recombinant or a dual infection. In this study, we identify the HIV F subtype for the first time in Colombia.

Adolescent↗
PubMed1997

Expression of protein kinase regulator genes in human ear and cloning of a gamma subtype of the 14-3-3 family of proteins.

We have used oligonucleotides corresponding to conserved regions of protein kinase regulators of 14-3-3 gene family as primers to amplify these genes from cDNAs constructed from the human fetal inner ear. Sequence characterization of clones revealed that the 14-3-3 cDNA library from the fetal inner ear has high abundance of clones encoding a protein kinase regulator (theta subtype), a member of 14-3-3 gene family, and relatively lower abundance of clones for two other members of the gene family. One of these genes is identical to the eta subtype of human 14-3-3 genes; there is no cloned gene for the other subtype in the human 14-3-3 gene family in the nucleic acid data bases. A sequence homology search revealed that the latter shared significant homology with the gamma subtype of the rat 14-3-3 family. On the basis of the sequence data, it appears that this clone represents a human homolog of the rat gamma subtype. The results demonstrate the expression of 14-3-3 genes in the inner ear, characterize a human homolog of the rat gamma subtype of 14-3-3, implicate these proteins in ear development, and indicate the utility of gene family polymerase chain reaction (PCR) for investigating gene expression in specific tissues.

14-3-3 Proteins↗
PubMed1992

Different interactions of interferon-alpha subtypes at the surface of epithelial and lymphoid cells.

The interaction of different interferon (IFN)-alpha subtypes with different cell types was investigated using a unique monoclonal antibody (MAb), I-4-A. This MAb reacts in immunoassays equally with IFN-alpha 2b and IFN-alpha 4a, but does not inhibit the binding of IFN to cell receptors. 125I-labeled I-4-A reacted with IFN-alpha 4a and IFN-alpha 2b bound to receptors on Daudi cells. However, in a "double assay" developed using Daudi cells to measure antiviral and antiproliferative activity, I-4-A neutralized both activities of IFN-alpha 4a, but neither of IFN-alpha 2b. Similarly, in studies on the activation of natural killer (NK) cells, I-4-A neutralized the effect of IFN-alpha 4a but not that of IFN-alpha 2b. In contrast, when cell lines other than lymphoid were studied, e.g., HEp 2 and WISH cells, I-4-A neutralized the antiviral activity of both IFN-alpha subtypes. The neutralization of one IFN-alpha subtype but not another on lymphoid cells suggests a difference either in the receptor-bound form of the subtypes, or in subsequent interactions prerequisite for activation of these cells. Furthermore, the neutralization of a particular IFN subtype, alpha 2b, on epithelial-derived but not lymphoid cells suggests differences in the IFN-receptor complex or the mechanisms of cell activation between these cell types. An implication from these studies is that some IFN-alpha subtypes can exert different functions on lymphoid and epithelial cells.

Amino Acid Sequence↗
PubMed2025

HallmarkGraph: a cancer hallmark informed graph neural network for classifying hierarchical tumor subtypes.

MOTIVATION: Accurate tumor subtype diagnosis is crucial for precision oncology, yet current methodologies face significant challenges. These include balancing model accuracy with interpretability and the high costs of generating multi-omics data in clinical settings. Moreover, there is a lack of validated models capable of classifying hierarchical tumor subtypes across a comprehensive pan-cancer cohort. RESULTS: We present a graph neural network, HallmarkGraph, the first biologically informed model developed to classify hierarchical tumor subtypes in human cancer. Inspired by cancer hallmarks, the model's architecture integrates transcriptome profiles and gene regulatory interactions to perform multi-label classification. We evaluate the model on a comprehensive pan-cancer cohort comprising 11 476 samples from 26 primary cancers with 405 subtypes up to eight levels. The model demonstrates exceptional performance, achieving 5-fold cross-validation accuracy between 85% and 99% for tumor subtypes labeled with increasing details of genomic information. It also shows good generalizability on a validation dataset of 887 samples, assessed using three metrics that consider tumor subtypes at individual, combined, and sample levels. Benchmarking and ablation experiments show that hallmark-based embeddings slightly influence model performance, while the integrated multilayer perceptron plays a significant role in determining classifier accuracy. Additionally, we use the SHAP method to link cancer hallmarks with genes, identifying key features that influence model decisions. Our findings present a biologically informed machine learning framework capable of tracking tumor transcriptomic trajectories and distinguishing inter- and intra-tumor heterogeneity in pan-cancer. This approach holds promise for enhancing cancer diagnostics. AVAILABILITY AND IMPLEMENTATION: HallmarkGraph is accessible at https://github.com/laixn/HallmarkGraph.

Humans↗
PubMed1995

DNA subtypes and fluconazole susceptibilities of Candida albicans isolates from the oral cavities of patients with AIDS.

Sixty-two Candida albicans isolates from the oral cavities of 28 patients with AIDS who were receiving fluconazole therapy were typed by restriction endonuclease analysis followed by pulsed-field gel electrophoresis; these isolates were then tested for fluconazole susceptibility by a standard broth dilution method. Sequential isolates (range, 2-4) were evaluated for 22 patients; only one isolate was evaluated for six patients. DNA subtyping revealed a total of 37 different DNA subtypes. Twelve (54.5%) of 22 patients with multiple episodes of oropharyngeal candidiasis were infected with a single DNA subtype throughout the observation period. Ten (45.5%) of 22 patients with multiple episodes of oropharyngeal candidiasis were infected with two or three DNA subtypes during the observation period. In vitro susceptibility tests revealed that MICs of fluconazole ranged from < or = 0.125 microgram/mL to 64 micrograms/mL, with an MIC50 of 0.5 microgram/mL and an MIC90 of 4 micrograms/mL. A significant increase in the MICs (fourfold or greater) of fluconazole for sequential C. albicans isolates was found for 66.6% of the patients infected with a single DNA subtype and for 50% of the patients infected with multiple DNA subtypes. Despite a limited number of patients and isolates, our data suggest that C. albicans isolates that are susceptible to fluconazole at MICs of > or = 8 micrograms/mL in vitro will be less susceptible in vivo to standard doses (100-200 mg/d) of this drug.

AIDS-Related Opportunistic Infections↗
PubMed1999

Encoding of Ca2+ signals by differential expression of IP3 receptor subtypes.

Inositol 1,4,5-trisphosphate (IP3) plays a key role in Ca2+ signalling, which exhibits a variety of spatio-temporal patterns that control important cell functions. Multiple subtypes of IP3 receptors (IP3R-1, -2 and -3) are expressed in a tissue- and development-specific manner and form heterotetrameric channels through which stored Ca2+ is released, but the physiological significance of the differential expression of IP3R subtypes is not known. We have studied the Ca2+-signalling mechanism in genetically engineered B cells that express either a single or a combination of IP3R subtypes, and show that Ca2+-signalling patterns depend on the IP3R subtypes, which differ significantly in their response to agonists, i.e. IP3, Ca2+ and ATP. IP3R-2 is the most sensitive to IP3 and is required for the long lasting, regular Ca2+ oscillations that occur upon activation of B-cell receptors. IP3R-1 is highly sensitive to ATP and mediates less regular Ca2+ oscillations. IP3R-3 is the least sensitive to IP3 and Ca2+, and tends to generate monophasic Ca2+ transients. Furthermore, we show for the first time functional interactions between coexpressed subtypes. Our results demonstrate that differential expression of IP3R subtypes helps to encode IP3-mediated Ca2+ signalling.

Adenosine Triphosphate↗