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Viruses Jan 2016Human T-cell leukemia virus type 1 (HTLV-1) was the first human retrovirus discovered. Studies on HTLV-1 have been instrumental for our understanding of the molecular... (Review)
Review
Human T-cell leukemia virus type 1 (HTLV-1) was the first human retrovirus discovered. Studies on HTLV-1 have been instrumental for our understanding of the molecular pathology of virus-induced cancers. HTLV-1 is the etiological agent of an adult T-cell leukemia (ATL) and can lead to a variety of neurological pathologies, including HTLV-1-associated-myelopathy/tropical spastic paraparesis (HAM/TSP). The ability to treat the aggressive ATL subtypes remains inadequate. HTLV-1 replicates by (1) an infectious cycle involving virus budding and infection of new permissive target cells and (2) mitotic division of cells harboring an integrated provirus. Virus replication initiates host antiviral immunity and the checkpoint control of cell proliferation, but HTLV-1 has evolved elegant strategies to counteract these host defense mechanisms to allow for virus persistence. The study of the molecular biology of HTLV-1 replication has provided crucial information for understanding HTLV-1 replication as well as aspects of viral replication that are shared between HTLV-1 and human immunodeficiency virus type 1 (HIV-1). Here in this review, we discuss the various stages of the virus replication cycle-both foundational knowledge as well as current updates of ongoing research that is important for understanding HTLV-1 molecular pathogenesis as well as in developing novel therapeutic strategies.
Topics: Animals; HTLV-I Infections; Human T-lymphotropic virus 1; Humans; Virus Replication
PubMed: 26828513
DOI: 10.3390/v8020031 -
PLoS Pathogens Feb 2023The complex retrovirus, human T-cell leukemia virus type 1 (HTLV-1), primarily infects CD4+ T-cells in vivo. Infectious spread within this cell population requires...
The complex retrovirus, human T-cell leukemia virus type 1 (HTLV-1), primarily infects CD4+ T-cells in vivo. Infectious spread within this cell population requires direct contact between virally-infected and target cells. The HTLV-1 accessory protein, HBZ, was recently shown to enhance HTLV-1 infection by activating intracellular adhesion molecule 1 (ICAM-1) expression, which promotes binding of infected cells to target cells and facilitates formation of a virological synapse. In this study we show that HBZ additionally enhances HTLV-1 infection by activating expression of myoferlin (MyoF), which functions in membrane fusion and repair and vesicle transport. Results from ChIP assays and quantitative reverse transcriptase PCR indicate that HBZ forms a complex with c-Jun or JunB at two enhancer sites within the MYOF gene and activates transcription through recruitment of the coactivator p300/CBP. In HTLV-1-infected T-cells, specific inhibition of MyoF using the drug, WJ460, or shRNA-mediated knockdown of MyoF reduced infection efficiency. This effect was associated with a decrease in cell adhesion and an intracellular reduction in the abundance of HTLV-1 envelope (Env) surface unit (SU) and transmembrane domain (TM). Lysosomal protease inhibitors partially restored SU levels in WJ460-treated cells, and SU localization to LAMP-2 sites was increased by MyoF knockdown, suggesting that MyoF restricts SU trafficking to lysosomes for degradation. Consistent with these effects, less SU was associated with cell-free virus particles. Together, these data suggest that MyoF contributes to HTLV-1 infection through modulation of Env trafficking and cell adhesion.
Topics: Humans; Basic-Leucine Zipper Transcription Factors; CD4-Positive T-Lymphocytes; Human T-lymphotropic virus 1; Retroviridae Proteins
PubMed: 36827461
DOI: 10.1371/journal.ppat.1011202 -
MSphere Sep 2020Bats are the reservoir for a large number of zoonotic viruses, including members of (severe acute respiratory syndrome coronavirus [SARS-CoV] and SARS-CoV-2), (Hendra...
Bats are the reservoir for a large number of zoonotic viruses, including members of (severe acute respiratory syndrome coronavirus [SARS-CoV] and SARS-CoV-2), (Hendra and Nipah viruses), (rabies virus), and (Ebola virus) as exemplars. Many retroviruses, such as human immunodeficiency virus, are similarly zoonotic; however, only infectious exogenous gammaretroviruses have recently been identified in bats. Here, viral metagenomic sequencing of samples from bats submitted for rabies virus testing, largely due to human exposure, identified a novel, highly divergent exogenous from a big brown bat () in South Dakota. The virus sequence, corresponding to deltaretrovirus (EfDRV), comprised a nearly complete coding region comprised of canonical 5'-----3' genes with 37% to 51% identity to human T-lymphotropic virus (HTLV), an infectious retrovirus that causes T-cell lymphoma. A putative gene with 27% identity to HTLV was located downstream of the gene along with a gene harbored in an alternative reading frame which possessed a conserved domain for an Epstein-Barr virus nuclear antigen involved in gene transactivation, suggesting a regulatory function similar to that of the deltaretrovirus gene. A TaqMan reverse transcriptase PCR (RT-PCR) targeting the gene identified 4/60 (6.7%) bats as positive for EfDRV, which, combined with a search of the genome that failed to identify sequences with homology to EfDRV, suggests that EfDRV is an infectious exogenous virus. As all known members of can cause malignancies and is widely distributed in the Americas, often with a colonial roosting behavior in human dwellings, further studies are needed to investigate potential zoonosis. Bats host a large numbers of viruses, many of which are zoonotic. In the United States, the big brown bat () is widely distributed and lives in small colonies that roost in cavities, often in human dwellings, leading to frequent human interaction. Viral metagenomic sequencing of samples from an bat submitted for rabies testing identified the first exogenous bat The deltaretrovirus (EfDRV) genome consists of the typical deltaretrovial 5'-----3' genes along with genes encoding two putative transcriptional transactivator proteins distantly related to the Tax protein of human T-cell lymphotrophic virus and nuclear antigen 3B of Epstein-Barr virus. Searches of the genome sequence failed to identify endogenous EfDRV. RT-PCR targeting the EfDRV gene identified 4/60 (6.7%) bats with positive results. Together, these results suggest that EfDRV is exogenous. As all members of are associated with T- and B-cell malignancies or neurologic disease, further studies on possible zoonosis are warranted.
Topics: Animals; Chiroptera; Deltaretrovirus; Gene Products, tax; Genome, Viral; Humans; RNA, Viral; South Dakota; United States; Zoonoses
PubMed: 32968009
DOI: 10.1128/mSphere.00902-20 -
Viruses Jun 2014Bovine leukemia virus (BLV) and human T-lymphotropic virus type 1 (HTLV-1) are closely related d-retroviruses that induce hematological diseases. HTLV-1 infects about 15... (Review)
Review
Bovine leukemia virus (BLV) and human T-lymphotropic virus type 1 (HTLV-1) are closely related d-retroviruses that induce hematological diseases. HTLV-1 infects about 15 million people worldwide, mainly in subtropical areas. HTLV-1 induces a wide spectrum of diseases (e.g., HTLV-associated myelopathy/tropical spastic paraparesis) and leukemia/lymphoma (adult T-cell leukemia). Bovine leukemia virus is a major pathogen of cattle, causing important economic losses due to a reduction in production, export limitations and lymphoma-associated death. In the absence of satisfactory treatment for these diseases and besides the prevention of transmission, the best option to reduce the prevalence of d-retroviruses is vaccination. Here, we provide an overview of the different vaccination strategies in the BLV model and outline key parameters required for vaccine efficacy.
Topics: Animals; Antibodies, Neutralizing; Antibodies, Viral; Cattle; Deltaretrovirus; Deltaretrovirus Infections; Enzootic Bovine Leukosis; HTLV-I Infections; Human T-lymphotropic virus 1; Humans; Leukemia Virus, Bovine; Vaccination; Vaccines, Attenuated; Viral Vaccines
PubMed: 24956179
DOI: 10.3390/v6062416 -
The New England Journal of Medicine Feb 1985
Topics: Acquired Immunodeficiency Syndrome; Antibodies, Viral; Deltaretrovirus; Disease Outbreaks; Ethics, Medical; Humans; Serologic Tests; United States
PubMed: 2982097
DOI: 10.1056/nejm198502213120829 -
International Journal of Biological... Dec 2010Viral oncogenes are responsible for oncogenesis resulting from persistent virus infection. Although different human tumor viruses express different viral oncogenes and... (Review)
Review
Viral oncogenes are responsible for oncogenesis resulting from persistent virus infection. Although different human tumor viruses express different viral oncogenes and induce different tumors, their oncoproteins often target similar sets of cellular tumor suppressors or signal pathways to immortalize and/or transform infected cells. Expression of the viral E6 and E7 oncogenes in papillomavirus, E1A and E1B oncogenes in adenovirus, large T and small t antigen in polyomavirus, and Tax oncogene in HTLV-1 are regulated by alternative RNA splicing. However, this regulation is only partially understood. DNA tumor viruses also encode noncoding RNAs, including viral microRNAs, that disturb normal cell functions. Among the determined viral microRNA precursors, EBV encodes 25 from two major clusters (BART and BHRF1), KSHV encodes 12 from a latent region, human polyomavirus MCV produce only one microRNA from the late region antisense to early transcripts, but HPVs appears to produce no viral microRNAs.
Topics: Adenoviridae; Deltaretrovirus; Herpesvirus 4, Human; Herpesvirus 8, Human; Humans; MicroRNAs; Oncogenic Viruses; Papillomaviridae; Polyomavirus; RNA Splicing; RNA, Untranslated; RNA, Viral
PubMed: 21152115
DOI: 10.7150/ijbs.6.730 -
The Brazilian Journal of Infectious... 2018Human T-lymphotropic viruses (HTLV) are Deltaretroviruses that infect millions of individuals worldwide via the same transmission routes as HIV. With the aim of exposing... (Review)
Review
Human T-lymphotropic viruses (HTLV) are Deltaretroviruses that infect millions of individuals worldwide via the same transmission routes as HIV. With the aim of exposing the possible re-emergence of HTLV in West Africa since discovery, a systematic review was carried out, focusing on the distribution of the virus types and significance of frequent indeterminate reports, while highlighting the need for mandatory routine blood screening. Capturing relevant data from discovery till date, sources searched were Google Scholar, CrossRef, NCBI (PubMed), MEDLINE, Research Gate, Mendeley, abstracts of Conferences and Proceedings, organization websites and reference lists of selected papers. A total of 2626 references were initially retrieved using search terms: Worldwide prevalence of HTLV, HTLV in Africa, HTLV in West Africa, HTLV subtypes, HTLV 3 and 4 in Africa, HTLV of African origin, HTLV seroindeterminate results, Spread of HTLV. These references were rigorously trimmed down to 76. Although evidence shows that HTLV is still endemic in the region, West Africa lacks recent epidemiological prevalence data. Thorough investigations are needed to ascertain the true cause of indeterminate Western Blot results. It is imperative that routine screening for HTLVs be mandated in West African health care facilities.
Topics: Africa, Western; Deltaretrovirus; Deltaretrovirus Infections; Female; Humans; Male; Prevalence; Risk Factors; Seroepidemiologic Studies
PubMed: 29879426
DOI: 10.1016/j.bjid.2018.05.003 -
Retrovirology Dec 2019Few years after HTLV-1 identification and isolation in humans, STLV-1, its simian counterpart, was discovered. It then became clear that STLV-1 is present almost in all... (Review)
Review
Few years after HTLV-1 identification and isolation in humans, STLV-1, its simian counterpart, was discovered. It then became clear that STLV-1 is present almost in all simian species. Subsequent molecular epidemiology studies demonstrated that, apart from HTLV-1 subtype A, all human subtypes have a simian homolog. As HTLV-1, STLV-1 is the etiological agent of ATL, while no case of TSP/HAM has been described. Given its similarities with HTLV-1, STLV-1 represents a unique tool used for performing clinical studies, vaccine studies as well as basic science.
Topics: Animals; Deltaretrovirus Infections; Disease Models, Animal; Female; HTLV-I Infections; Human T-lymphotropic virus 1; Humans; Male; Phylogeny; Primates; Simian T-lymphotropic virus 1
PubMed: 31843020
DOI: 10.1186/s12977-019-0503-0 -
Viruses Jul 2011Human T cell leukemia/lymphoma virus Type 1 and 2 (HTLV-1 and HTLV-2), together with their simian counterparts (STLV-1, STLV-2), belong to the Primate T lymphotropic... (Review)
Review
Human T cell leukemia/lymphoma virus Type 1 and 2 (HTLV-1 and HTLV-2), together with their simian counterparts (STLV-1, STLV-2), belong to the Primate T lymphotropic viruses group (PTLV). The high percentage of homologies between HTLV-1 and STLV-1 strains, led to the demonstration that most HTLV-1 subtypes arose from interspecies transmission between monkeys and humans. STLV-3 viruses belong to the third PTLV type and are equally divergent from both HTLV-1 and HTLV-2. They are endemic in several monkey species that live in West, Central and East Africa. In 2005, we, and others reported the discovery of the human homolog (HTLV-3) of STLV-3 in two asymptomatic inhabitants from South Cameroon whose sera exhibited HTLV indeterminate serologies. More recently, two other cases of HTLV-3 infection in persons living in Cameroon were reported suggesting that this virus is not extremely rare in the human population living in Central Africa. Together with STLV-3, these human viral strains belong to the PTLV-3 group. A fourth HTLV type (HTLV-4) was also discovered in the same geographical area. The overall PTLV-3 and PTLV-4 genomic organization is similar to that of HTLV-1 and HTLV-2 with the exception of their long terminal repeats (LTRs) that contain only two 21 bp repeats. As in HTLV-1, HTLV-3 Tax contains a PDZ binding motif while HTLV-4 does not. An antisense transcript was also described in HTLV-3 transfected cells. PTLV-3 molecular clones are now available and will allow scientists to study the viral cycle, the tropism and the possible pathogenicity in vivo. Current studies are also aimed at determining the prevalence, distribution, and modes of transmission of these viruses, as well as their possible association with human diseases. Here we will review the characteristics of these new simian and human retroviruses, whose discovery has opened new avenues of research in the retrovirology field.
Topics: Africa, Central; Animals; Deltaretrovirus Infections; Gene Products, tax; Haplorhini; Human T-lymphotropic virus 3; Humans; Phylogeny; Prevalence; Simian T-lymphotropic virus 3
PubMed: 21994771
DOI: 10.3390/v3071074 -
The Yale Journal of Biology and Medicine 1990Modifications in donor screening and the introduction of laboratory testing of donated blood for anti-HIV-1 and anti-HTLV-I have resulted in a significant reduction in... (Review)
Review
Modifications in donor screening and the introduction of laboratory testing of donated blood for anti-HIV-1 and anti-HTLV-I have resulted in a significant reduction in the risks of retroviral infections from blood transfusion. Presently, the American Red Cross detects an average of eight carriers of human immunodeficiency virus, type 1 (HIV-1) per 100,000 otherwise acceptable blood donors (0.008 percent), compared with an average of 35 per 100,000 (0.035 percent) when testing for HIV-1 antibodies began in 1985. Surveillance studies in the United States indicate a small likelihood that HIV-2 carriers will pass current screening procedures and be accepted as blood donors. Even if an HIV-2-infected person were to be accepted as a blood donor, there is a 42-92 percent likelihood that this person's blood would be detected as infective for HIV-2 and excluded because of serological cross-reactions that occur in the EIA for HIV-1 antibodies. During 1989, which was the first year that donated blood was routinely tested for antibodies to human T-lymphotropic virus, type I (HTLV-I) in the United States, approximately nine in 100,000 donors (0.009 percent) were confirmed positive for antibodies to HTLV-I, and their donated blood was excluded. Subsequent testing has revealed that a significant number of these persons whose sera was reactive by the HTLV-I EIA were, in fact, infected by HTLV-II. Epidemiological studies of human retroviral infections (HIV-1, HIV-2, HTLV-I, and HTLV-II) continue to provide important data and direction for improving criteria for qualifying blood donors.
Topics: Blood Donors; Deltaretrovirus Infections; HIV Antigens; HIV Infections; HIV Seropositivity; HIV-1; HIV-2; Human T-lymphotropic virus 1; Human T-lymphotropic virus 2; Humans; Retroviridae Infections; Risk Factors; Transfusion Reaction
PubMed: 1981409
DOI: No ID Found