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PubMed2026

IL1RAP Is Associated With an Inflammation-Immunity-Related State in Skin Cutaneous Melanoma: Integrative Evidence From Pan-Cancer Data and Melanoma Immunotherapy Cohorts.

BACKGROUND: The crosstalk between inflammation and immunity plays a central role in tumor progression, immune evasion, and therapeutic response. Interleukin-1 receptor accessory protein (IL1RAP) is a key adaptor in inflammatory signaling, yet its immunological relevance and clinical implications in skin cutaneous melanoma (SKCM) remain largely unexplored. METHODS: We performed an integrative analysis combining pan-cancer and melanoma-focused datasets. Bulk transcriptomic, single-cell, spatial transcriptomic, genomic alteration, pharmacogenomic, and clinical survival data were obtained from TCGA, GTEx, GEO, ENA, and other public resources. IL1RAP expression was evaluated across cancer types in relation to diagnostic performance, immune subtypes, survival outcomes, functional pathway activity, immune-genomic states, somatic alterations, and drug-response metrics. Melanoma-focused analyses examined immune infiltration, methylation-derived tumor-infiltrating lymphocyte (MeTIL) scores, and exploratory survival associations in five treatment cohorts; the survival groups were defined using cohort-specific optimal cutoffs rather than median splits. RESULTS: IL1RAP expression differed between tumor and normal tissues in multiple cancers, although the direction and magnitude varied by cancer type. Pan-cancer survival associations were likewise context dependent. Single-cell and spatial transcriptomic resources indicated cell-type and spatial heterogeneity of IL1RAP expression within tumor microenvironments. Pathway, immune-genomic, and pharmacogenomic analyses identified exploratory associations with functional states, genomic features, and drug-response metrics. In SKCM, IL1RAP expression was associated with several immune-infiltration estimates and higher MeTIL scores. Across five melanoma immunotherapy cohorts, the direction and magnitude of the overall survival associations varied substantially. CONCLUSIONS: This retrospective integrative analysis suggests that IL1RAP may mark an inflammation-immunity-related state in SKCM. The heterogeneous associations across cancers and melanoma treatment cohorts support further validation but do not establish IL1RAP as a causal regulator, a treatment-response predictor, or a therapeutic target.

IL1RAP↗

PubMed1989

Changes in the bovine herpesvirus 1 genome during acute infection, after reactivation from latency, and after superinfection in the host animal.

Three subtypes, as defined by HindIII restriction endonuclease (RE) analysis patterns, of bovine herpesvirus 1 (BHV 1) were used to inoculate seronegative, BHV 1-free cattle. These included: infectious bovine rhinotracheitis virus (IBRV), subtype 1.1; infectious pustular vulvovaginitis virus (IPPV) isolate K22, subtype 1.2b; and IPVV isolate FI, subtype 1.2a. Nasal, vaginal, and buffy coat samples were taken for virus isolation from each animal. RE analysis was done on virus isolates collected during acute infection, after reactivation from latency, and after reactivation followed by superinfection with a subtype of BHV 1 that differed from the primary inoculation virus. Changes occurred in the BHV 1 genome after only 1 passage in the host animal, and varied from tissue to tissue within the same animal. Viruses reactivated from latency also displayed genome variability. Only animals that received IPVV as the primary inoculation virus were successfully superinfected. After superinfection, cattle shed both superinfecting and reactivated viruses, and genome variability was observed. These data suggest that the application of RE analysis in diagnostic and epidemiologic studies of BHV 1 is limited to analysis between types and subtypes, and is not applicable for the examination of isolates from within a BHV 1 subtype.

Acute Disease↗

PubMed2003

Classification of pediatric acute lymphoblastic leukemia by gene expression profiling.

Contemporary treatment of pediatric acute lymphoblastic leukemia (ALL) requires the assignment of patients to specific risk groups. We have recently demonstrated that expression profiling of leukemic blasts can accurately identify the known prognostic subtypes of ALL, including T-cell lineage ALL (T-ALL), E2A-PBX1, TEL-AML1, MLL rearrangements, BCR-ABL, and hyperdiploid karyotypes with more than 50 chromosomes. As the next step toward developing this methodology into a frontline diagnostic tool, we have now analyzed leukemic blasts from 132 diagnostic samples using higher density oligonucleotide arrays that allow the interrogation of most of the identified genes in the human genome. Nearly 60% of the newly identified subtype discriminating genes are novel markers not identified in our previous study, and thus should provide new insights into the altered biology underlying these leukemias. Moreover, a proportion of the newly selected genes are highly ranked as class discriminators, and when incorporated into class-predicting algorithms resulted in an overall diagnostic accuracy of 97%. The performance of an array containing the identified discriminating genes should now be assessed in frontline clinical trials in order to determine the accuracy, practicality, and cost effectiveness of this methodology in the clinical setting.

Algorithms↗

PubMed1997

Diabetes: from phenotypes to genotypes.

Diabetes mellitus comprises a heterogeneous group of diseases which have chronic hyperglycaemia in common as well as the resulting microvascular, macrovascular and neurological complications of this condition. Familial studies have provided strong evidence for the existence of genetic determinants in the different types of diabetes. In particular, monozygotic twin studies have indicated a higher rate of concordance in non-insulin-dependent (NIDDM) than in insulin-dependent diabetes mellitus (IDDM). In IDDM, 8 susceptibility loci have been identified, notably the HLA complex and insulin promotor gene. Rigorous family studies have identified monogenic subtypes representing 10-15% of all NIDDM: MODY2 related to glucokinase gene mutations, MODY1 and MODY3 secondary to mutation of hepatic nuclear factors, and diabetes resulting from deletion or mutation of mitochondrial DNA. Most NIDDM result from polygenic heredity, and susceptibility genes conducive to increased receptivity to deleterious environmental influences are now under investigation, such as beta 3 adrenergic receptor, FABP2 and OB. Precise analysis of phenotypes in the remaining families or systematic screening of the genome could allow the genes of each subtype to be identified. Finally, susceptibility genes for the increased severity and frequency of vascular complications have been identified, such as angiotensin converting enzyme, aldose reductase and aldehyde dehydrogenase genes. This progress has been facilitated by developments in molecular biology.

Age of Onset↗

PubMed1997

Characteristic pattern of chromosomal gains and losses in marginal zone B cell lymphoma detected by comparative genomic hybridization.

Marginal zone B cell lymphoma (MZBCL) represents a distinct subtype of B cell non-Hodgkin's lymphoma, which has been recently recognized and defined as a disease entity. We investigated 25 cases (18 at primary diagnosis and seven during the course of disease) of MZBCL by comparative genomic hybridization (CGH) and compared these results with cytogenetic, fluorescence in situ hybridization (FISH), and Southern blot data. Twenty of the 25 cases (80%) showed gains (total 49) or losses (total 15) of genetic material. In extranodal, nodal, and splenic MZBCL, material of chromosomes 3 (52% of cases), 18 (32%), X (24%), and 1q (16%) was most frequently gained, whereas losses predominantly involved chromosomes 17 (16%) and 9 (12%). High-level amplifications involving the regions 18q21-23 and 18q21-22, respectively, were detected in two cases. Gains of chromosomes 1q and 8q and losses of chromosome 17 or 17p occurred more frequently in relapsed or progressive lymphomas. For all of the frequently affected chromosomes, CGH allowed narrowing of the relevant subregions including 3q21-23, 3q25-29 and 18q21-23. By Southern blot analysis, the BCL2, BCL6, and CMYC proto-oncogenes were found to be a part of the over-represented regions in two cases, one case, and two cases, respectively, with gains involving 18q, 3q or 8q. In 13 cases, CGH revealed chromosomal imbalances which were not detected by cytogenetic analysis but could be confirmed by FISH or Southern blot analysis in all cases investigated. On the other hand, CGH failed to detect trisomy 3, trisomy 18, and deletion 7q in three cases with a low proportion of tumor cells bearing these abnormalities, as shown by interphase FISH. The characteristic pattern of chromosomal gains and losses detected in this study confirms the distinct nature of MZBCL and may point to chromosomal regions involved in the pathogenesis of these neoplasms.

Adult↗

PubMed2002

Identification of two CRF11-cpx genomes and two preliminary representatives of a new circulating recombinant form (CRF13-cpx) of HIV type 1 in Cameroon.

Recombination is an efficient mechanism of HIV-1 to generate genetic variability. Some of the recombinant forms of HIV-1 that have been described are of epidemic importance, and they are referred to as circulating recombinant forms (CRFs). In this study, we characterized four HIV-1 isolates from Cameroon that had previously been classified as subtype J in the protease gene and as subtype A in the env C2-V5 region. Analyses of the nearly complete genomes revealed that two of the samples (95CM-1816 and 96CM-4496) had the same recombinant structure as CRF11-cpx. The two remaining samples (96CM-1849 and 96CM-4164) constituted a new recombinant virus variant with genomic regions identified as subtypes A, G, J, and CRF01-AE. This mosaic virus structure was found in two individuals who had no direct epidemiological relationship, and may thus represent a new CRF. The fragments that were classified as subtype J in the new recombinant form were more related to subtype J regions of the CRF11-cpx sequences than to the reference strains of subtype J. The complex structures of CRF11-cpx and our new recombinant form, which are both the result of at least four recombination events, exemplify the coming difficulties in characterizing the internal relationships and origins of future recombinant HIV-1 strains. The new recombinant structure has been designated CRF13-cpx in the Los Alamos HIV Sequence Database.

Cameroon↗

PubMed2003

Complete nucleotide sequences of the genomes of two Brazilian specimens of human T lymphotropic virus type 2 (HTLV-2).

We report the complete nucleotide sequences of the genomes of two human T cell lymphotropic viruses type 2 (HTLV-2) isolated from a Kayapó Indian (K96 isolate) and from an inhabitant of an urban region in the south of Brazil (RP329 isolate). The general structure of the K96 and RP329 genomes did not differ from that of other HTLV-2 genomes described in the literature. The K96 genome consisted of 8955 bp and the RP329 genome consisted of 8964 bp. The general similarity between the nucleotide sequences of the K96 and RP329 genomes was 99.4%. Comparison between the nucleotide sequences of the K96 and RP329 genomes and the nucleotide sequences of isolates considered to be HTLV-2 prototypes of subtype 2a (Mo isolate), 2b (NRA isolate), and 2d (Efe2 isolate) showed a global similarity of 98.8, 95.6, and 93.3%, respectively, for the RP329 isolate, and of 99.1, 95.6, and 93.3%, respectively, for the K96 isolate. Phylogenetic analysis permitted the classification of the K96 and RP329 isolates as HTLV-2 subtype 2a. Detailed phylogenetic analyses of the LTR, env, and Tax regions showed that the Brazilian isolates tend to form a distinct phylogenetic subgroup within subtype 2a, previously called HTLV-2c, which differs from the subtype 2a isolates found in North America, Europe, and Africa. The K96 genome is the first HTLV-2 genome obtained from a Brazilian Indian that was completely sequenced, whereas the RP329 genome represents the first specimen derived from an inhabitant of a Brazilian urban region who was not coinfected with HIV-1.

Amino Acid Sequence↗

PubMed1998

Cloning, expression, pharmacology and tissue distribution of the mouse somatostatin receptor subtype 5.

The gene encoding the mouse somatostatin receptor subtype 5 has been isolated from a genomic library and the mRNA start point mapped to position -95 relative to the translational start codon. The promoter region is devoid of TATA and CAAT boxes but contains putative binding sites for AP-1, AP-2 and SP1 and response elements for glucocorticoids (GRE) and phorbol esters (TRE). The encoded receptor protein with a predicted molecular weight of 42.5 kDa is comprised of 385 amino acids and thus contains 22 and 21 amino acids more than rat and human counterparts. The extra amino acids are caused by another translational initiation codon located further upstream. In the region of overlap the mouse somatostatin receptor subtype 5 displays 96.7% sequence identity to the rat and 81.7% to the human homologue. Application of somatostatin-14 and -28 to human embryonic kidney cells expressing the recombinant receptor resulted in the inhibition of forskolin-stimulated adenylyl cyclase with comparable EC50 values. Consistent with the observed sequence relationship, the mouse somatostatin receptor subtype 5 displays a pharmacological profile that resembles the rat homologue more closely than the human counterpart. mRNA for the mouse somatostatin type 5 receptor has been detected in pituitary, kidney, spleen and ovary and, to a lesser extent, in brain, stomach, intestine and thymus but was not observed in heart, pancreas and liver.

Amino Acid Sequence↗

PubMed1971

Herpes vimplex virus: genome size and redundancy studied by renaturation kinetics.

Herpes simplex virus subtype 1 deoxyribonucleic acid (DNA) was sheared in a French press to uniform fragments, denatured by heating, then allowed to reassociate. The renaturation reaction followed second-order kinetics with a single rate constant indicating that at least 95% of the genome was unique and that repetitive sequences, if present, were not detectable by this technique. The kinetic complexity of the herpes simplex genome was determined by DNA renaturation kinetics to be (95 +/- 1) x 10(6) daltons. Since this value is in excellent agreement with the molecular weight of viral DNA [(99 +/- 5) x 10(6) daltons] obtained from velocity sedimentation studies, it is concluded that virions contain only one species of double-stranded DNA molecules 95 x 10(6) to 99 x 10(6) daltons in molecular weight.

Base Sequence↗

PubMed2005

[Genetic variability of hepatitis B virus isolates among population of Shuryskarsky area of Yamal-Nenets autonomous region].

UNLABELLED: The purpose of this work was to determine occurrence of serological markers of hepatites B and to describe subtypes of a superficial antigen and genotypes of hepatitis B virus (HBV) isolates among indigenous population of Yamal-Nenets Autonomous Region (YNAR), Russia. METHODS: We investigated 657 serum samples from inhabitants of Shuryskarsky area of YNAR. ELISA method was used to define the hepatitis B markers: HBsAg, anti-HBs (total) and anti-HBc (IgG and IgM). The HBsAg-positive samples were PCR-tested for the presence of HBV DNA. Genotyping of isolates was by sequencing of the Pre-Sl/Pre-82/S region of HBV genome and phylogenetic analysis. Definition of HBsAg subtypes was executed by two methods: ELISA with subtype-specific monoclonal antibodies and S-gene nucleotide sequence analysis. RESULTS: The following occurrence of hepatitis B markers was observed: HBsAg - 3.2%, anti-HBs (total) - 36.2%, anti-HBc IgG - 30.3%, anti-HBc IgM - 1.6%. Frequency of carrying even one of the markers in the observed population was 47.5%. HBV DNA was found in 17 HBsAg-positive samples. Pre-SI, Pre-S2 and S regions sequences were determined for all HBV DNA-positive samples. The phylogenetic analysis showed an accessory of all investigated HBV isolates to genotype D. HBsAg subtypes distribution appeared the following: ayw2 - 23.5%, ayw3 - 70.6%, adw2 - 5.9%. Results of definition of the subtype ELISA method and by the analysis of S gene nucleotide sequences have coincided in 10/11 (90.1%) cases. CONCLUSIONS: The indigenous population of Shuryskarsky area of YNAR belongs to groups with average HBV carrying. Absolute domination of genotype D (subtypes ayw2, ayw3 and adw2) was revealed. High percentage of concurrence of HBsAg subtypes detected by the ELISA method and method of the analysis of S gene primary structure (90%) was observed. Sequencing of HBV S-gene is preferable to define HBsAg subtypes.

Adolescent↗

PubMed2006

Performance of the automated Abbott RealTime HIV-1 assay on a genetically diverse panel of specimens from Brazil.

The combination of automated sample preparation and real-time RT-PCR for measurement of HIV-1 viral load has the potential to significantly enhance throughput, reduce operator-associated error, and increase assay sensitivity and dynamic range. In this study, RNA was extracted from the plasma of 91 HIV-1 seropositive Brazilian blood donors using the Abbott m2000sp automated sample preparation system. Viral loads measured using the RealTime HIV-1 (RealTime HIV-1) assay and the Abbott m2000rt instrument were compared to values obtained in the LCx HIV RNA quantitative assay. Subtype was determined for 89 of 91 specimens by sequence/phylogenetic analysis of three genomic regions: gag p24, pol integrase, and env gp41. The panel included 69 subtype B, 1 C, 2 F, and 17 recombinant strains. Eighty-seven specimens were quantified by both assays. Two specimens were quantified only in RealTime HIV-1. Two additional specimens below the detection limit of both assays were also negative on PCR amplification. Viral load results were highly correlated, and good agreement was observed between assays with 90% of values within 0.5 log(10)copies/ml. The RealTime HIV-1 assay and m2000 system offer the advantages of automation while providing reliable quantification of diverse HIV strains.

Automation↗

PubMed2002

Genomic organization and regulation of a human 7-helix transmembrane receptor which is expressed in pulmonary epithelial cells and induced in hypoxia.

The genetic, regulatory, and tissue-specific characterization of G-protein-coupled receptors is substantial since it contributes to the identification of the natural ligand which may influence basic physiological processes and cell function. Here we explored the genomic structure of a human orphan seven-transmembrane receptor which presents the human homologue of a receptor which has been controversially identified as a rat adrenomedullin receptor subtype. Based on the cDNA sequence a 3.4 kb genomic DNA fragment was isolated. Sequencing of the fragment and comparison studies revealed an intron of 544 bp in the 5' untranslated region, followed by a second exon encoding the receptor protein of 404 amino acids. The gene is localized on chromosome 12q. The 5' regulatory region contains several SP1, AP2, and CAAT sites as well as hypoxia responsive elements (HRE) both in the 5' and 3' regulatory region. RT-PCR with intron spanning primers demonstrated mRNA signals in various tissues, especially in lung. Characterizing the histological expression pattern in lung sections by nonisotopic in situ hybridization, a strong signal of receptor mRNA was identified in pulmonary epithelial cells of bronchi and alveoli. Analysis of the two human pulmonary epithelial cell lines, H23 and A549, showed significant mRNA induction of this receptor subtype in hypoxia.

Cell Hypoxia↗

PubMed2005

Identification of a novel HIV-1 circulating ADG intersubtype recombinant form (CRF19_cpx) in Cuba.

Circulating recombinant forms (CRFs) represent a substantial proportion of HIV-1 isolates in the global pandemic. Characterization of HIV-1 genetic forms, including CRFs, may be relevant to studies on molecular epidemiology, recombination, superinfection, vaccine development, and antiretroviral therapy. This study analyzes near complete genomes of 4 epidemiologically unlinked viruses from Cuba, originally characterized as D/A intersubtype recombinants in pol and env segments. The genomes of 3 viruses exhibited virtually coincident mosaic structures, with multiple segments of subtypes A, D, and G and uniform phylogenetic clustering with each other along the genome. These results allow us to define a new CRF (CRF19_cpx). The 4th analyzed Cuban virus was recombinant between CRF19_cpx and CRF18_cpx (which also circulates in Cuba). CRF19_cpx exhibited homology to an AG intersubtype recombinant virus from Cameroon (CM53392) along approximately 5 kb and clustered with a subtype D virus from Gabon (G109) in gag. Four other viruses from central or west Africa were also phylogenetically related to CRF19_cpx in env fragments. These results allow us to define CRF19_cpx as a second novel CRF of African origin circulating in Cuba, to identify putative representative viruses of its parental strains, and to characterize a unique CRF18/CRF19 recombinant virus.

Adult↗

PubMed2026

Baseline Plasma Cell-Free and Circulating Tumor DNA Across Lymphoma Subtypes and Its Prognostic Impact in Diffuse Large B-Cell Lymphoma.

BACKGROUND: Circulating tumor DNA (ctDNA) analysis enables real‑time assessment of the tumor burden and genomic complexity in lymphomas. However, real‑world evidence across lymphoma subtypes is limited. METHODS: We analyzed cell‑free DNA (cfDNA) and ctDNA data from 336 consecutive patients with newly diagnosed Hodgkin or non-Hodgkin lymphoma in 2022 and evaluated their prognostic impact in diffuse large B‑cell lymphoma (DLBCL). RESULTS: We detected somatic alterations in 248 of 336 patients (73.8%). DLBCL and follicular lymphoma showed the highest variant prevalences and ctDNA burdens. Epigenetic regulators, including KMT2D, CREBBP, TET2, and HIST1H1E, constituted the dominant class of genes with recurrent alterations. Plasma variant profiles closely mirrored publicly available, tissue‑based next-generation sequencing datasets. The baseline ctDNA burden correlated with adverse clinical features, and ctDNA positivity was associated with failure to achieve complete remission. In DLBCL, elevated cfDNA (top quartile) and a high International Prognostic Index (IPI) were independently associated with shorter overall and progression‑free survival. However, the total variant count per patient was not significantly associated with survival after adjustment. CONCLUSIONS: Baseline plasma cfDNA and ctDNA assessments are feasible in routine practice and recapitulate tissue-variant landscapes. Elevated cfDNA concentrations-but not the total variant count-were independently associated with survival in DLBCL, providing prognostic information beyond the IPI and supporting integration of plasma-based biomarkers into multiparameter risk models. Gene‑level ctDNA associations should be regarded as exploratory and hypothesis‑generating.

Cell-free DNA↗

PubMed1999

[Prevalence of types of hepatitis C virus in Spanish blood donors: results of a state-based multicenter study. Spanish Group for the Study of Blood Donors with Risk of HCV Transmission].

BACKGROUND: The prevalences established up to the present in Spain for the different types of hepatitis C virus are based on data obtained in populations in which the nature of the population itself may have based the data in favor of certain types of the virus. The study of seropositive blood donors identified through screening of blood donations may provide prevalences closer to the truth among the general population. MATERIALS AND METHODS: Typing of genomes in samples from 441 donors was performed using the blood bank generated during the multicenter study performed by the Spanish Study Group of Blood Donors with Risk of Transmission of the Hepatitis C Virus. The antibodies present were typed in the seropositive samples in the above donors and in 337 more in whom a viral genoma was not detected. RESULTS: In total, the infection was typed in 685 donors. On analysis of the results corresponding to 386 donors, whose number and distribution by autonomous communities were previously fixed to represent all of Spain, type 1 was largely the more prevalent (85.5%) followed by types 3 (4.4%), 2 (4.1%), 4 (3.4%) and 5 (0.5%) and by a group of apparent mixed infections which altogether represented 2.1% of the total. Among the donors in whom the genomes were typed, infectious due to the 1b subtype (78% of the 441 samples genotypes) clearly predominated. The participation of the different types of type 1 was significantly greater in those lacking antibodies detectable versus epitopes codified in the NS4 region of the viral genome. CONCLUSIONS: This study avoids some bias in sampling which may have affected previous studies and provides data which should more closely approach the real prevalence in the general Spanish population. Thus, it should provide a better base of comparison for any study on the distribution of the types of the hepatitis C virus in selected populations or others performed during tha investigation of outbreaks of hepatitis C virus infection.

Blood Donors↗

PubMed1998

Antigenic diversity of hepatitis B virus strains of genotype F in Amerindians and other population groups from Venezuela.

The adw4 subtype of hepatitis B virus (HBV) belongs to a unique genomic group (genotype F) representing the original HBV strains from the New World. Data regarding the prevalence of this subtype among HBV carriers in South America are, however, scarce, and those concerning HBV genotype F are based on only a few samples from Latin America. In this study, serum samples were obtained from 141 hepatitis B surface antigen (HBsAg) carriers from Amerindians and urban populations from Venezuela. The HBsAg subtype was identified with monoclonal antibodies in 105 samples, and the HBV genotype was identified by reverse-phase hybridization with DNA fragments in 58 samples. The adw4 subtype was highly prevalent in the population studied (75%); among the Amerindians, the prevalence was 97%. The adw2 subtype was also present (10%), while other subtypes (ayw3 and ayw4) were only occasionally found. The HBV subtype was associated with the expected genotype in most cases (80%), and thus genotype F was highly prevalent. Sequencing of viral strains that gave genotypes unpredicted by the HBsAg subtyping confirmed seven of them as belonging to not previously described genotype-subtype associations: namely, adw2 and ayw4 within genotype F.

Amino Acid Substitution↗

PubMed2000

Characterization of a virtually full-length human immunodeficiency virus type 1 genome of a prevalent intersubtype (C/B') recombinant strain in China.

A molecular epidemiology study was conducted among more than 100 human immunodeficiency virus type 1 (HIV-1) subtype C seropositive intravenous drug users (IDUs) from China. Genotyping based on the envelope C2V3 coding region revealed the highest homology of the most prevalent virus strains circulating throughout China to subtype C sequences of Indian origin. Based on these results, a virtually full-length genome representing the most prevalent class of clade C strains circulating throughout China was directly amplified from peripheral blood mononuclear cells of a selected HIV-infected IDU and subcloned. Sequence analysis identified a mosaic structure, suggesting extensive intersubtype recombination events between genomes of the prevalent clade C and (B')-subtype Thai virus strains of that geographic region. Recombinant Identification Program analysis and phylogenetic bootstrapping suggested that there were 10 breakpoints (i) in the gag-pol coding region, (ii) in vpr and at the 3' end of the vpu gene, and (iii) in the nef open reading frame. (B')-sequences therefore include (i) several insertions in the gag-pol coding region; (ii) 3'-vpr, the complete vpu gene, and the first exons of tat and rev; and (iii) the 5' half of the nef gene. Breakpoints located in the vpr/vpu coding region as well as in the nef gene of 97cn54 were found at almost identical positions of all subtype C strains isolated from IDUs living in different areas of China, suggesting a common ancestor for the C/B' recombinant strains. More than 50% of well-defined subtype B-derived cytotoxic T-lymphocyte epitopes within Gag and Pol and 10% of the known epitopes in Env were found to exactly match sequences within in this clade C/B' chimeric reference strain. These results may substantially facilitate a biological comparison of clade C-derived reference strains as well as the generation of useful reagents supporting vaccine-related efforts in China.

Amino Acid Sequence↗

PubMed1980

Electrophoretic migration rate differences of polypeptides of human influenza A viruses: partial analysis of the genome of influenza vaccine recombinant viruses.

Electrophoretic migration rate differences were detected in high resolution SDS polyacrylamide gels for nucleoprotein (NP), matrix protein (M), non structural protein (NS1), haemagglutinin (HA) annd, less regularly, for the polymerase polypeptides P1, P2 and P3 induced by different influenza A viruses. The technique allowed parental assignation of the corresponding genes in certain recombinant viruses including A/PR/8/34 (H0N1)--A/HK/117/77 (H1N1), A/Okuda/57 (H2N2)--A/HK/119/77 (H1N1) and A/Leningrad/76 (H3N2)--A/Leningrad/46 (H0N1) recombinants, thus considerably extending the technique which had been applied previously to A/PR/8/34--A/HK/68 (H3N2) only. Agreement in gene assignment between three recombinants of the former group and 11 of 17 recombinants in the A/Okuda/57--A/HK/119/77 group was noted when the data obtained using the polypeptide method was correlated with a direct genetic analysis by others using RNA:RNA hybridisation techniques. The polypeptide method appears to have wide application for the initial rapid analysis of influenza A virus recombinants obtained using parents of different influenza subtypes although complete analysis of the total genome requires the use of RNA hybridisation techniques. Two additional virus induced proteins are described, a phosphorylated form of NS 1 and a non structual polypeptide with a molecular weight of 16K daltons.

Electrophoresis, Polyacrylamide Gel↗