The majority of htlv1infected subjects remain asymptomatic carriers. Genome wide analysis of human genes transcriptionally and. The structural proteins gag, pro, and pol are encoded in the unspliced form of viral mrna, whereas the env protein is encoded in singly spliced viral. Human immunodeficiency virus type 1 genome activation. Complete sequences of the human tcell leukemia virus type. Complete nucleotide sequences of the genomes of two. Discovery of an endogenous deltaretrovirus in the genome.
Dna methylation modulates hres1p28 expression in b cells from patients with lupus. The k96 genome is the first htlv2 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 hiv1. Human tcell leukemia virus type 1 htlv1 has two transacting regulator genes, tax and rex, in the px region. Citeseerx complete nucleotide sequence of the italian. The virus tool assigns taxonomic names to sequences from eukaryotic viruses and phages. By constructing a database to connect htlv1 genetic sequences and. The recent discoveries of novel human tlymphotropic virus type 3 htlv3 and highly divergent simian tlymphotropic virus type 3 stlv3 subtype d viruses from two different monkey species in southern cameroon suggest that the diversity and crossspecies transmission of these retroviruses are much greater than currently appreciated. The tar sequence is unique for the primate lentiviruses, and its rna serves as the binding site for tat 12, 16. The question mark indicates the putative accessory gene region. Genetic differences between htlv1 strains are not associated with differing clinical outcomes of htlv1 infections 17, 18. Htlv1 is a retrovirus that has infected 1020 million people worldwide, and is considered the first retrovirus to be causal for adult tcell leukemia atl. We identified the variants in the coding regions of the genome of the different clinical profiles, however, no statistical relation was detected. Complete genome sequence of human tcell lymphotropic type.
Additionally, hbz suppresses host nfkappabdriven transcription mediated by host rela as well as transcription of some classical nfkappab target genes, including il8, il2ra, irf4, vcam1, and vegfa. Table downloads are also available via the genome browser ftp server. Pdf complete genome sequence of central africa human t. The designed probes were completely specified for the 122base fragment of the tax region of the htlv 1 genome. The tax sequence of the sf26 sample showed high identity with the rare htlv1b subtype, the central africa subtype. Isolation of the genomic dna sequences flanking the htlv1 using an adaptorligated pcr. The consensus sequence of minerva is shown schematically in scale. Download scientific diagram structure of the htlv1 proviral genome and.
Next, the ltr sequences were submitted to the htlv 1 automated subtyping tool version 1. Tools for working with sequences lists all our online tools, organized by function. The role of htlv1 clonality, proviral structure, and. Determination of the total nucleotide sequence of the htlv genome has revealed no typical onc gene acquired from the cellular sequence 9,10. Characterization and sequencing of prototypic human t. So far, there is not a complete genome sequence of this htlv subtype.
The genomic analysis showed that all characteristic regions and genes of a prototypic htlv1 virus are conserved. Since htlv 1 is a retrovirus, the viral rna genome is reverse transcribed. A bonnet macaque a monkey present in india was found infected with stlv1. At the moment 8889 distinct taxonomic names are assigned based on 11845 reference.
Author summary primate tlymphotropic viruses type 1 ptlv1 are complex retroviruses infecting both human htlv1 and simian stlv1 hosts. Tcell leukemia virus 1 strain japan atk1 subtype a htlv1 pan proteome fasta. After reverse transcription and integration into the genome, htlv1. Here, we report the genome of a new stlv1 subtype b from a 43yearold male gorilla with tcell lymphoma. A retrovirus belongs to a group of rna viruses that insert a dna copy of their genome into a host cell and replicates. The htlv1 database is a database with clinical and patological informations about the data in htlv 1 molecular epidemiology database the htlv1 database contains clinical, phylogenetics and epidemiological data from htlv1 sequences.
To maintain latency and avoid immune detection in vivo, htlv 1 minimizes expression of genes on the plusstrand of the integrated provirus but allows constitutive expression of the minusstrand gene, which maintains clonal persistence. The htlv strains from the reactive samples were typed by using an inhouse pcr and sequencing of the htlv tax region. The tax gene is a transacting transcriptional activator of the long terminal repeat ltr and also of the cellular gene for il2rthe latter seems to explain initiation of abnormal growth of htlv1 infected cells. There are four lineages of primate tcell lymphocytic viruses human tcell lymphocytic virus htlvsimian tcell lymphocytic virus stlv, which are further divided into subtypes.
The cpg depletion of the human genome, in addition to the reported sequence context dependency of cpg depletion in influenza virus and its possible link to components of the human immune system inspired us to explore the sequence contexts of cpg depletion and methylation in the hiv1 genome. Human t cell leukemia virus types 1 and 2 htlv1 and htlv2 are genetically related complex retroviruses that are capable of immortalizing human tcells in vitro and establish lifelong persistent infections in vivo. To perform molecular analysis, the fastq files, from each generated viral genome, were trimmed and mapped to the htlv1 reference sequence atk1 j02029 using the highest sensitivity and finetuning settings, followed by editing and manual alignment of the mapped reads, these steps were performed using the geneious software kearse et al. Htlv1 lineages are divided in four clades, a cosmopolitan, b central african group, c melanesian group and d new central african group. Human t celllymphotropic virus 1 htlv1 is known as an enveloped retrovirus. Htlv1 gene expression in the absence of hbz mrna or. The htlv1 genome has three regions that codify the precursors gag. This was based on three reactions i a pcr with the gp46f1gp46r1 nucleotide primers. The retrovirus human tlymphotropic virus type 1 htlv 1 causes inflammatory and malignant diseases in humans. The nature of the htlv1 provirus in naturally infected. Rapid isolation of viral integration site reveals frequent. Despite possession of similar structural features to. However, only 2 htlv1 subtypes a and 1b have had their whole genomes sequenced to date.
Although htlv1 has a compact rna genome, it has evolved elaborate mechanisms to maximize its coding potential. The nature of the htlv1 provirus in naturally infected individuals. These sequences were genotyped as cosmopolitan subtype, transcontinental subgroup. Probe 1 and probe 2 were made of 22 and 30 bases, respectively. In turn, the resultant genetic instability can also alter the proviral genome, which is frequently mutated or deleted, allowing escape from the host immune response. In this study, using primary peripheral blood mononuclear cells, we report a genome wide analysis of human genes transcriptionally and posttranscriptionally regulated by the htlvi. Comparative virology of htlv1 and htlv2 retrovirology. It has been shown that the persistence and pathogenesis of these viruses depend on the expression of small, accessory proteins. Contributes to the regulation of viral rna transcription by interacting with host proteins involved in transcriptional activation such as atf4, or creb1, and by inhibiting their activity. Hres1 htlv1 related endogenous sequence gene gtr ncbi. Schematic representation of the htlv1 genome download. Ngs reads aligned to htlv1 are shown below the reference genome.
Here, we report the complete htlv1 provirus genome sequence of oatl9, a novel htlv1ebvinfected bcell line isolated from the acute type atl patient. Pdf complete sequence of human t cell leukemia virus. Hbz htlv1 basic zipper factor human tcell leukemia. For these experiments, we used a cell line that contained the htlv. In spite of these apparent similarities, htlv1 and htlv2 exhibit a significantly different pathogenic potential. Shortly after the discovery of htlv1, human tcell leukemia virus type 2 htlv2 was isolated from a patient with hairy cell leukemia. The taxonomic rank which gets assigned is based on availability of reference genomes in refseq, and is mostly at species level. The complete nucleotide sequence of a human tcell lymphotropic virus type ii isolate htlviigu from an italian injecting drug user was obtained, representing the first entire sequence of a european htlvii isolate. Stability of the htlv1 glycoprotein 46 gp46 gene in an. A cosmopolitan b central african group c melanesian group d new central african group description and significance.
The retrovirus htlv1 inserts an ectopic ctcfbinding site. The noncoding region ltr was used to identify motifs for transcription factors using the tfscan plugin in geneious r6 software. The rex gene is a posttranscriptional regulator accumulating gag. Atl which is a malignant transformation of tlymphocytes, and htlv1 associated myelopathytropical spastic paraparesis. The human tcell leukemia virus type 1 htlv1 is a retrovirus causing an aggressive tcell malignancy, adult tcell leukemia atl. The project generated and characterized 31 complete htlv1 genome sequences.
The impact of htlv1 on the cellular genome sciencedirect. Reference strain human tlymphotropic virus 1 sequence genome proteome host human. Barreto fk, araujo tha, rego ffa, alcantara lc 2017 a fully annotated genome sequence of human tcell lymphotropic virus type 1 htlv 1. Identification of these rna may reveal new targets and increase our understanding of htlvi pathogenesis. Complete genome sequence of central africa human tcell lymphotropic virus subtype 1b. A visualization of sequencing reads aligned to the htlv1 provirus in ed cell line.
A schematic figure of the reference genome, integrated htlv1, and flanking host genomic region is shown at the top. After that, the probes were functionalized with aunps in average size of 12 nm. To maintain latency and avoid immune detection in vivo, htlv1 minimizes expression of genes on the plusstrand of the integrated provirus but allows constitutive expression of the minusstrand gene, which maintains clonal persistence. Genome browser uses jbrowse to display diverse data about the hiv1 genome and proteome.
Source of cpg depletion in the hiv1 genome molecular. A public htlv1 molecular epidemiology database for sequence. The retrovirus human tlymphotropic virus type 1 htlv1 causes inflammatory and malignant diseases in humans. Absence of accessory genes in a divergent simian t. Fali t, le dantec c, thabet y, jousse s, hanrotel c. There are six human retroviruses that have been identified so far. Fullgenome characterization of simian tcell leukemia. This is version 27 of the entry and version 1 of the sequence.
The general key functions for each of the genes at the protein level are listed to the. Complete sequence of human t cell leukemia virus type 1 in atll patients from northeast iran, mashhad revealed a prematurely terminated protease and an elongated px open reading frame iii. Human t cell leukemia virus type 1 htlv1 was the first discovered human retrovirus and the etiologic agent of adult tcell leukemia and htlv1associated myelopathytropical spastic paraparesis. Here, using a sensitive highthroughput method, we quantified clonality in 197 atl cases, identified.
Similar to other retroviruses, htlv1 carries a diploid rna genome comprising 9032 nucleotides that is reversetranscribed into doublestranded dna that integrates into host genome as a provirus. Htlv1 is able to escape from hosts defense mechanisms. Genetic characterization of the complete genome of a. Alignment and building of clone consensus sequence, as well as subsequent comparison to the prototype htlv1 sequence and translational analysis. Of note, htlv1 infection is endemic in brazil, and the prevalence varies across different regions of brazil. The discovery of a functional ctcf binding site within the px region of the htlv1 genome adds a new dimension to the importance of the flanking genome to proviral transcription. Htlv 1 increases genomic instability by direct actions on the host genome.
To date, there is only one fulllength htlv1 subtype b genome available. This page contains links to sequence and annotation data downloads for the genome assemblies featured in the ucsc genome browser. The htlviigu genome was more similar to the htlviibnra isolate 984% and htlvilbg12 982% than to htlviiamo 95. Different types of retroviruses human retroviruses these are the types that affect humans most commonly. Both direct and indirect htlv 1 driven mechanisms lead to changes in the host cell dna. So far, there is not a complete genome sequence of.
The tax sequence of the sf26 sample showed high identity with the rare htlv 1b subtype, the central africa subtype. Human t celllymphotropic virus 1 htlv1 is known as an enveloped retrovirus which comprises two equal copies of singlestranded rna virion genome with positive polarity. Human tcell lymphotropic virus type 1 or human tlymphotropic virus type 1 htlvi, also called the adult tcell lymphoma virus type 1, is a retrovirus of the human tlymphotropic virus htlv family that has been implicated in several kinds of diseases including very aggressive adult tcell lymphoma atl, htlviassociated myelopathy, uveitis, strongyloides stercoralis hyperinfection and. The virushost chimeric reads are shown in black circles. The presence of a 12bp deletion in the htlv1 genome from patient si1, localized to a region which codes for portions of the viral gag and protease. The data on the complete genome sequences of the htlv1 strains found in brazil are scant. Complete genome sequence of central africa human tcell. Human tlymphotropic virus 1 htlv1 is divided into 4 subtypes. The comparison with htlv1 genome structure is shown for clarity, some htlv1 genes were omitted.
The life cycle of htlv1 is similar to that of other retroviruses. Nonspecific integration of the htlv provirus genome into. So, in addition to the standard repertoire of structural proteins and enzymes shared by all retroviridae gag, pol, pro and env, the 3region of the htlv1 genome px region also encodes a number of accessory genes. The human tlymphotropic virus, human tcell lymphotropic virus, or human tcell leukemialymphoma virus htlv family of viruses are a group of human retroviruses that are known to cause a type of cancer called adult tcell leukemialymphoma and a demyelinating disease called htlv1 associated myelopathytropical spastic paraparesis hamtsp. The position of orfs and other genomic features are indicated. Htlv1 is also present in southern africa, southern india, northern iran, the aboriginal populations of northern australia, and many islands in the tropics. Structure of the htlv1 proviral genome and gene product key.
The sequence output may be downloaded in fasta format and the. A characteristic of htlv1 is that it is mainly spread through celltocell contact, although the exact mechanism is still a matter of debate igakura et al. This is version 105 of the entry and version 1 of the sequence. Human tcell leukemia virus 1 strain japan atk1 subtype a htlv1 status. Complete genome sequence of human tcell lymphotropic type 1 from patients with different clinical profiles, including infective dermatitis. Long segment detection of htlv1 genome based on the. Comparison of the genetic organization, expression. Molecular characterization of human tcell lymphotropic. The sequencing data generated on ion torrent pgm platform were assembled and mapped against the reference htlv 1 genome.
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