scholarly journals Functional and Structural Segregation of Overlapping Helices in HIV-1

2021 ◽  
Author(s):  
Maliheh Safari ◽  
Bhargavi Jayaraman ◽  
Shumin Yang ◽  
Cynthia Smith ◽  
Jason D Fernandes ◽  
...  
Keyword(s):  
The Other ◽  
Overlapping Genes ◽  
Selective Force ◽  
Therapeutic Targeting ◽  
Coding Regions ◽  
Functional Assays ◽  
Selection Experiments ◽  
Selective Forces ◽  
Hiv 1 ◽  
Overlapped Region

Overlapping coding regions balance selective forces between multiple genes. One possible division of nucleotide sequence is that the predominant selective force on a particular nucleotide can be attributed to just one gene. While this arrangement has been observed in regions in which one gene is structured and the other is disordered, we sought to explore how overlapping genes balance constraints when both protein products are structured over the same sequence. We use a combination of sequence analysis, functional assays and selection experiments to examine an overlapped region in HIV-1 that encodes helical regions in both Env and Rev. We find that functional segregation occurs even in this overlap, with each protein spacing its functional residues in a manner that allows a mutable non-binding face of one helix to encode important functional residues on a charged face in the other helix. Additionally, our experiments reveal novel and critical functional residues in Env and have implications for the therapeutic targeting of HIV-1.

scholarly journals Prevalence of Non-B HIV-1 Subtypes in North Italy and Analysis of Transmission Clusters Based on Sequence Data Analysis

2019 ◽  
Vol 8 (1) ◽  
pp. 36 ◽  
Author(s):  
Giovanni Lorenzin ◽  
Franco Gargiulo ◽  
Arnaldo Caruso ◽  
Francesca Caccuri ◽  
Emanuele Focà ◽  
...  
Keyword(s):  
Public Health ◽  
Sequence Data ◽  
Human Mobility ◽  
Heterosexual Couples ◽  
Molecular Surveillance ◽  
Coalescence Model ◽  
Coding Regions ◽  
Hiv Epidemic ◽  
Viral Subtypes ◽  
Hiv 1

HIV-1 diversity is increasing in European countries due to immigration flows, as well as travels and human mobility, leading to the circulation of both new viral subtypes and new recombinant forms, with important implications for public health. We analyzed 710 HIV-1 sequences comprising protease and reverse-transcriptase (PR/RT) coding regions, sampled from 2011 to 2017, from naive patients in Spedali Civili Hospital, Brescia, Italy. Subtyping was performed by using a combination of different tools; the phylogenetic analysis with a structured coalescence model and Makarov Chain Monte Carlo was used on the datasets, to determine clusters and evolution. We detected 304 (43%) patients infected with HIV-1 non-B variants, of which only 293 sequences were available, with four pure subtypes and five recombinant forms; subtype F1 (17%) and CRF02_AG (51.1%) were most common. Twenty-five transmission clusters were identified, three of which included >10 patients, belonging to subtype CRF02_AG and subtype F. Most cases of alleged transmission were between heterosexual couples. Probably due to strong migratory flows, we have identified different subtypes with particular patterns of recombination or, as in the case of the subtype G (18/293, 6.1%), to a complete lack of relationship between the sequenced strains, revealing that they are all singletons. Continued HIV molecular surveillance is most important to analyze the dynamics of the boost of transmission clusters in order to implement public health interventions aimed at controlling the HIV epidemic.

Two separate regions of the extrachromosomal ribosomal deoxyribonucleic acid of Tetrahymena thermophila enable autonomous replication of plasmids in Saccharomyces cerevisiae

1981 ◽  
Vol 1 (6) ◽  
pp. 535-543
Author(s):  
G B Kiss ◽  
A A Amin ◽  
R E Pearlman
Keyword(s):  
Saccharomyces Cerevisiae ◽  
High Frequency ◽  
Deoxyribonucleic Acid ◽  
Tetrahymena Thermophila ◽  
The Other ◽  
Yeast Cells ◽  
Origin Of Replication ◽  
Autonomous Replication ◽  
Coding Regions ◽  
Dna Fragment

Plasmids containing the nontranscribed central and terminal, but not the coding, regions of the extrachromosomal ribosomal deoxyribonucleic acid (rDNA) of Tetrahymena thermophila are capable of autonomous replication in Saccharomyces cerevisiae. These plasmids transform S. cerevisiae at high frequency; transformants are unstable in the absence of selection, and plasmids identical to those used for transformation were isolated from the transformed yeast cells. One plasmid contains a 1.85-kilobase Tetrahymena DNA fragment which includes the origin of bidirectional replication of the extrachromosomal rDNA. The other region of Tetrahymena rDNA allowing autonomous replication of plasmids in S. cerevisiae is a 650-base pair, adenine plus thymine-rich segment from the rDNA terminus. Neither of these Tetrahymena fragments shares obvious sequence homology with the origin of replication of the S. cerevisiae 2-microns circle plasmid or with ars1, an S. cerevisiae chromosomal replicator.

scholarly journals Complete chloroplast genome of Hordeum brevisubulatum: Genome organization, synonymous codon usage, phylogenetic relationships, and comparative structure analysis

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261196
Author(s):  
Guangxin Cui ◽  
Chunmei Wang ◽  
Xiaoxing Wei ◽  
Hongbo Wang ◽  
Xiaoli Wang ◽  
...  
Keyword(s):  
Phylogenetic Relationships ◽  
Genome Engineering ◽  
De Novo ◽  
Synonymous Codon ◽  
Northern China ◽  
Synonymous Codon Usage ◽  
The Other ◽  
Coding Regions ◽  
Cp Genome ◽  
Hordeum Brevisubulatum

Background Hordeum brevisubulatum, known as fine perennial forage, is used for soil salinity improvement in northern China. Chloroplast (cp) genome is an ideal model for assessing its genome evolution and the phylogenetic relationships. We de novo sequenced and analyzed the cp genome of H. brevisubulatum, providing a fundamental reference for further studies in genetics and molecular breeding. Results The cp genome of H. brevisubulatum was 137,155 bp in length with a typical quadripartite structure. A total of 130 functional genes were annotated and the gene of accD was lost in the process of evolution. Among all the annotated genes, 16 different genes harbored introns and the genes of ycf3 and rps12 contained two introns. Parity rule 2 (PR2) plot analysis showed that majority of genes had a bias toward T over A in the coding strand in all five Hordeum species, and a slight G over C in the other four Hordeum species except for H. bogdanil. Additionally, 52 dispersed repeat sequences and 182 simple sequence repeats were identified. Moreover, some unique SSRs of each species could be used as molecular markers for further study. Compared to the other four Hordeum species, H. brevisubulatum was most closely related to H. bogdanii and its cp genome was relatively conserved. Moreover, inverted repeat regions (IRa and IRb) were less divergent than other parts and coding regions were relatively conserved compared to non-coding regions. Main divergence was presented at the SSC/IR border. Conclusions This research comprehensively describes the architecture of the H. brevisubulatum cp genome and improves our understanding of its cp biology and genetic diversity, which will facilitate biological discoveries and cp genome engineering.

scholarly journals Identification of SERINC5-001 as the Predominant Spliced Isoform for HIV-1 Restriction

2017 ◽  
Vol 91 (10) ◽  
Author(s):  
Xianfeng Zhang ◽  
Tao Zhou ◽  
Jie Yang ◽  
Yumei Lin ◽  
Jing Shi ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Transmembrane Domain ◽  
The Other ◽  
Stable Expression ◽  
Membrane Localization ◽  
Plasma Membrane Localization ◽  
Immunodeficiency Virus ◽  
Alternatively Spliced ◽  
Anti Hiv ◽  
Hiv 1

ABSTRACT Among the five serine incorporator (SERINC) family members, SERINC5 (Ser5) was reported to strongly inhibit HIV-1 replication, which is counteracted by Nef. Ser5 produces 5 alternatively spliced isoforms: Ser5-001 has 10 putative transmembrane domains, whereas Ser5-004, -005, -008a, and -008b do not have the last one. Here, we confirmed the strong Ser5 anti-HIV-1 activity and investigated its isoforms' expression and antiviral activities. It was found that Ser5-001 transcripts were detected at least 10-fold more than the other isoforms by real-time quantitative PCR. When Ser5-001 and its two isoforms Ser5-005 and Ser5-008a were expressed from the same mammalian expression vector, only Ser5-001 was stably expressed, whereas the others were poorly expressed due to rapid degradation. In addition, unlike the other isoforms, which are located mainly in the cytoplasm, Ser5-001 is localized primarily to the plasma membrane. To map the critical determinant, Ser5 mutants bearing C-terminal deletions were created. It was found that the 10th transmembrane domain is required for Ser5 stable expression and plasma membrane localization. As expected, only Ser5-001 strongly inhibits HIV-1 infectivity, whereas the other Ser5 isoforms and mutants that do not have the 10th transmembrane domain show very poor activity. It was also observed that the Nef counteractive activity could be easily saturated by Ser5 overexpression. Thus, we conclude that Ser5-001 is the predominant antiviral isoform that restricts HIV-1, and the 10th transmembrane domain plays a critical role in this process by regulating its protein stability and plasma membrane targeting. IMPORTANCE Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) express a small protein, Nef, to enhance viral pathogenesis in vivo. Nef has an important in vitro function, which is to make virus particles more infectious, but the mechanism has been unclear. Recently, Nef was reported to counteract a novel anti-HIV host protein, SERINC5 (Ser5). Ser5 has five alternatively spliced isoforms, Ser5-001, -004, -005, -008a, and -008b, and only Ser5-001 has an extra C-terminal transmembrane domain. We now show that the Ser5-001 transcripts are produced at least 10-fold more than the others, and only Ser5-001 produces stable proteins that are targeted to the plasma membrane. Importantly, only Ser5-001 shows strong anti-HIV-1 activity. We further demonstrate that the extra transmembrane domain is required for Ser5 stable expression and plasma membrane localization. These results suggest that plasma membrane localization is required for Ser5 antiviral activity, and Ser5-001 is the predominant isoform that contributes to the activity.

scholarly journals The evolution of regulatory elements in the emerging promoter variant strains of HIV-1

2021 ◽  
Author(s):  
Disha Bhange ◽  
Nityanand Prasad ◽  
Swati Singh ◽  
Harshit Kumar Prajapati ◽  
Shesh Prakash Maurya ◽  
...  
Keyword(s):  
Viral Latency ◽  
Regulatory Elements ◽  
The Other ◽  
Clinical Samples ◽  
Latent Reservoir ◽  
Viral Gene ◽  
Viral Promoter ◽  
Reservoir Characteristics ◽  
Hiv 1

AbstractIn a multicentric, observational, investigator-blinded, and longitudinal clinical study of 764 ART-naïve subjects, we identified nine different promoter-variant strains of HIV-1 subtype C (HIV-1C) emerging in the Indian population, with some of these variants being reported for the first time. Unlike several previous studies, our work here focuses on the evolving viral regulatory elements, not coding sequences. The emerging viral strains contain additional copies of the existing transcription factor binding sites (TFBS), including TCF-1α/LEF-1, RBEIII, AP-1, and NF-κB, created by sequence duplication. The additional TFBS are genetically diverse and may blur the distinction between the modulatory region of the promoter and the viral enhancer. In a follow-up analysis, we found trends, but not significant associations between any specific variant promoter and prognostic markers, probably because the emerging viral strains might not have established mono infections yet. Illumina sequencing of four clinical samples containing a co-infection indicated the domination of one strain over the other and establishing a stable ratio with the second strain at the follow-up time-points. Since a single promoter regulates viral gene expression and constitutes the master regulatory circuit with Tat, the acquisition of additional and variant copies of the TFBS may significantly impact viral latency and latent reservoir characteristics. Further studies are urgently warranted to understand how the diverse TFBS profiles of the viral promoter may modulate the characteristics of the latent reservoir, especially following the initiation of antiretroviral therapy.Significance StatementA unique conglomeration of TFBS enables the HIV-1 promoter to accomplish two diametrically opposite functions – transcriptional activation and transcriptional silencing. The various phases of viral latency - establishment, maintenance, and reversal - collectively determine the replication fitness of individual viral strains. A profound variation in the TFBS composition of the viral promoter may significantly alter the viral latency properties and the latent reservoir characteristics. Although the duplication of certain TFBS remains a quality unique to HIV-1C, the high-level genetic recombination of HIV-1 may promote the transfer of such molecular properties to the other HIV-1 subtypes. The emergence of several promoter-variant viral strains may make the task of a ‘functional cure’ more challenging in HIV-1C.

INCIDENCE OF HIV-1 AND HIV-2 ANTIBODIES IN HEMOPHILIACS

1987 ◽  
Author(s):  
W Schramm ◽  
L G Gürtler ◽  
H Pohlmann ◽  
I Weigel ◽  
J Eberie ◽  
...  
Keyword(s):  
The Other ◽  
Clotting Factor ◽  
Test Results ◽  
Clotting Factors ◽  
Negative Results ◽  
Group 12 ◽  
Hiv Test ◽  
In The Beginning ◽  
Anti Hiv ◽  
Hiv 1

The presence of antibodies to HIV-1 (anti-HIV-1) was tested in 167 hemophiliacs surveyed and treated at Munich hemophilia center. Increasing numbers of HIV infected patients were observed in the years 1981 to 1986 from 0% to 51,5% (86 positive patients in January 1987 of 167 followed patients). Most of the seroconver-sions occured between 1982 and 1984. The 150 clinically severe affected hemophiliacs (F-VIII-levels up to 5% and need of replacement therapy) showed positive HIV-test results in 55,3% (83 patients) and negative results in 44,7% (67 patients). 5 patients died since 1981, one because of AIDS. 17 patients were not seen since 1984, 14 of those belong to the severly affected group, 12 of them were negative. Since spring 1985 only heat or chemically treated clotting factor preparations are used for substitution. Despite this still 5 seroconversions were observed. Two may be attributed to the use of a preparation heat inactivated in dry state, this preparation is no longer used. The other 3 seroconversions possibly were caused by an occasional use of an noninactivated preparation in the beginning of the change to inactivated clotting factor preparations. 38 of the anti-HIV-1 positive sera were tested for the presence of HIV-2 antibodies also. The methods were ELISA,immunofluorescence and immunoblot. HIV-2 (LAV-2) for these tests was kindly provided by L. Montagnier. Antibodies specific for HIV-2 antigens were not detected, but crossreactions were observed between anti-HIV-1 with HIV-2 antigens particularly epitopes on HIV-2-p27.The data indicate that the use of adequately inactivated clotting factors can prevent infection of hemophilia patients by this route and that HIV-2 was not present in the clotting factor preparations used for the substitution of this group of patients. The incidence of full blown AIDS since 1981 in our group of hemophiliacs is still low (1,2%).

scholarly journals Predicting Coding Potential from Genome Sequence: Application to Betaherpesviruses Infecting Rats and Mice

2005 ◽  
Vol 79 (12) ◽  
pp. 7570-7596 ◽  
Author(s):  
Luciano Brocchieri ◽  
Thomas N. Kledal ◽  
Samuel Karlin ◽  
Edward S. Mocarski
Keyword(s):  
Genome Annotation ◽  
Mrna Splicing ◽  
Overlapping Genes ◽  
Genome Sequences ◽  
Protein Coding ◽  
Coding Regions ◽  
Translation Signals ◽  
Rats And Mice ◽  
Coding Potential ◽  
Exon Gene

ABSTRACT Prediction of protein-coding regions and other features of primary DNA sequence have greatly contributed to experimental biology. Significant challenges remain in genome annotation methods, including the identification of small or overlapping genes and the assessment of mRNA splicing or unconventional translation signals in expression. We have employed a combined analysis of compositional biases and conservation together with frame-specific G+C representation to reevaluate and annotate the genome sequences of mouse and rat cytomegaloviruses. Our analysis predicts that there are at least 34 protein-coding regions in these genomes that were not apparent in earlier annotation efforts. These include 17 single-exon genes, three new exons of previously identified genes, a newly identified four-exon gene for a lectin-like protein (in rat cytomegalovirus), and 10 probable frameshift extensions of previously annotated genes. This expanded set of candidate genes provides an additional basis for investigation in cytomegalovirus biology and pathogenesis.

scholarly journals Characterization of a Major Histocompatibility Complex Class II X-Box-Binding Protein Enhancing Tat-Induced Transcription Directed by the Human Immunodeficiency Virus Type 1 Long Terminal Repeat

2000 ◽  
Vol 74 (19) ◽  
pp. 8989-9001 ◽  
Author(s):  
Carlo Mischiati ◽  
Giordana Feriotto ◽  
Monica Borgatti ◽  
Patrizio Giacomini ◽  
Roberto Gambari
Keyword(s):  
Human Immunodeficiency Virus ◽  
Transcription Factors ◽  
Major Histocompatibility Complex ◽  
Class Ii ◽  
The Other ◽  
Nuclear Proteins ◽  
Histocompatibility Complex ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The X-box element present within the promoter region of genes belonging to the major histocompatibility complex (MHC) plays a pivotal role in the expression of class II molecules, since it contains the binding sites for several well-characterized transcription factors. We have analyzed a randomly selected compilation of viral genomes for the presence of elements homologous to the X box of the HLA-DRA gene. We found that human immunodeficiency virus type 1 (HIV-1) shows the highest frequency of X-like box elements per 1,000 bases of genome. Within the HIV-1 genome, we found an X-like motif in the TAR region of the HIV-1 long terminal repeat (LTR), a regulative region playing a pivotal role in Tat-induced HIV-1 transcription. The use of a decoy approach for nuclear proteins binding to this element, namely, XMAS (X-like motif activator sequence), performed by transfection of multiple copies of this sequence into cells carrying an integrated LTR-chloramphenicol acetyltransferase construct, suggests that this element binds to nuclear proteins that enhance Tat-induced transcription. In this report we have characterized two proteins, one binding to the XMAS motif and the other to the flanking regions of XMAS. Mobility shift assays performed on crude nuclear extracts or enriched fractions suggest that similar proteins bind to XMAS from HIV-1 and the X box of the HLA-DRA gene. Furthermore, a UV cross-linking assay suggests that one protein of 47 kDa, termed FAX (factor associated with XMAS)-1, binds to the XMAS of HIV-1. The other protein of 56 kDa was termed FAX-2. In a decoy ex vivo experiment, it was found that sequences recognizing both proteins are required to inhibit Tat-induced HIV-1 LTR-driven transcription. Taken together, the data reported in this paper suggest that XMAS and nearby sequences modulate Tat-induced HIV-1 transcription by binding to the X-box-binding proteins FAX-1 and FAX-2. The sequence homology between XMAS and X box is reflected in binding of a common protein, FAX-1, and similar functional roles in gene expression. To our knowledge, this is the first report showing that transcription factors binding to the X box of the MHC class II genes enhance the transcription of HIV-1.

scholarly journals Experience and Mathematical Knowledge

2017 ◽  
Vol 21 (2) ◽  
pp. 209-222
Author(s):  
Rodolfo Gaeta
Keyword(s):  
Mathematical Knowledge ◽  
A Priori ◽  
The Other ◽  
Human Knowledge ◽  
Human Beings ◽  
Common View ◽  
Abstract Entities ◽  
Selection Experiments ◽  
Main Tenet ◽  
Previous Learning

According to a very common view, the main tenet of empiricism is the conviction that all human knowledge derives from sensory experience. But classic philosophers representing empiricism hold that mathematical knowledge is a priori. Mill intended to demonstrate that the laws of arithmetic and geometry have inductive origins. But Frege and others authors showed that Mill’s arguments were wrong. Benacerraf held that, since mathematical objects are abstract entities, they could not have any causal relationship with human beings, so they cannot be known by us. On the other hand, biology and psychology show that in animals and human creatures we can find innate behaviours, in accordance with the theory on natural selection. Experiments performed by Wynn and by other psychologists strongly support that very young babies can determine the results of simple arithmetical operations without any previous learning. We conclude that there are convincing reasons to accept the rationalist thesis about the a priori character of mathematical knowledge.

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