Human T-Lymphotropic Viruses (HTLV)

Martins, Marina Lobato; Andrade, Rafaela Gomes; Nédir, Bernardo Hinkelmann; Barbosa-Stancioli, Edel Figueiredo

doi:10.5772/36333

Cited by 4 publications

(5 citation statements)

References 48 publications

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“…HTLV-1, HTLV-2, HTLV-3, and HTLV-4 are the four major subtypes of HTLV identified to date. These group of viruses not only cause malignancy but also other inflammatory and immunosuppressive diseases [1,2]. HTLVs are enveloped viruses with a diameter ranging from 80 to 100 nm and within the HTLV virions, the reverse transcriptase (RT), integrase, protease viral enzymes, and capsid proteins form complexes with the two covalently bonded genomic RNA strands [3,4].…”

Section: Introductionmentioning

confidence: 99%

“…Among the four major subtypes of HTLV identified to date, the pathogenic roles of HTLV-1 and HTLV-2 in the human body are well-studied to date compared to HTLV-3 and HTLV-4. This group of viruses are transmitted through bodily fluids like semen, blood and milk [2]. HTLV-1, in particular, is the most life-threatening member of this viral family, causing fatal ATL in approximately 5% of the infected cases that characterizes high blood circulation, lymph node swelling and immunosuppression [7,8].…”

Section: Introductionmentioning

confidence: 99%

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An immunoinformatics and extended molecular dynamics approach for designing a polyvalent vaccine against multiple strains of Human T-lymphotropic virus (HTLV)

Moin,

Rani,

Ullah

et al. 2023

PLoS ONE

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Human T-lymphotropic virus (HTLV), a group of retroviruses belonging to the oncovirus family, has long been associated with various inflammatory and immunosuppressive disorders. At present, there is no approved vaccine capable of effectively combating all the highly pathogenic strains of HTLV that makes this group of viruses a potential threat to human health. To combat the devastating impact of any potential future outbreak caused by this virus group, our study employed a reverse vaccinology approach to design a novel polyvalent vaccine targeting the highly virulent subtypes of HTLV. Moreover, we comprehensively analyzed the molecular interactions between the designed vaccine and corresponding Toll-like receptors (TLRs), providing valuable insights for future research on preventing and managing HTLV-related diseases and any possible outbreaks. The vaccine was designed by focusing on the envelope glycoprotein gp62, a crucial protein involved in the infectious process and immune mechanisms of HTLV inside the human body. Epitope mapping identified T cell and B cell epitopes with low binding energies, ensuring their immunogenicity and safety. Linkers and adjuvants were incorporated to enhance the vaccine’s stability, antigenicity, and immunogenicity. Initially, two vaccine constructs were formulated, and among them, vaccine construct-2 exhibited superior solubility and structural stability. Molecular docking analyses also revealed strong binding affinity between the vaccine construct-2 and both targeted TLR2 and TLR4. Molecular dynamics simulations demonstrated enhanced stability, compactness, and consistent hydrogen bonding within TLR-vaccine complexes, suggesting a strong binding affinity. The stability of the complexes was further corroborated by contact, free energy, structure, and MM-PBSA analyses. Consequently, our research proposes a vaccine targeting multiple HTLV subtypes, offering valuable insights into the molecular interactions between the vaccine and TLRs. These findings should contribute to developing effective preventive and treatment approaches against HTLV-related diseases and preventing possible outbreaks. However, future research should focus on in-depth validation through experimental studies to confirm the interactions identified in silico and to evaluate the vaccine’s efficacy in relevant animal models and, eventually, in clinical trials.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

An immunoinformatics and extended molecular dynamics approach for designing a polyvalent vaccine against multiple strains of Human T-lymphotropic virus (HTLV)

Moin,

Rani,

Ullah

et al. 2023

PLoS ONE

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“…Therefore, considerable research needs to be conducted to develop a treatment method for the HTLV-1 infection. The HTLV-1 protease cleaves a viral polyprotein precursor into individual mature proteins in the life cycle of HTLV-1 . Characterizing the catalytic mechanism of HTLV-1 protease is essential to designing inhibitors of this enzyme in order to prevent viral replication and provide a possible cure for the HTLV-1-associated diseases.…”

Section: Introductionmentioning

confidence: 99%

Catalytic Mechanism of Human T-Cell Leukemia Virus Type 1 Protease Investigated by Combined QM/MM Molecular Dynamics Simulations

Petrillo

Dinh

Vogt

et al. 2023

J. Chem. Inf. Model.

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Combined quantum mechanical and molecular mechanical (QM/MM) molecular dynamics simulations were performed to investigate the catalytic mechanism of human T-cell leukemia virus type 1 (HTLV-1) protease, a retroviral aspartic protease that is a potential therapeutic target for curing HTLV-1-associated diseases. To elucidate the proteolytic cleavage mechanism, we determined the two-dimensional free energy surfaces of the HTLV-1 protease-catalyzed reactions through various possible pathways. The free energy simulations suggest that the catalytic reactions of the HTLV-1 protease occur in the following sequential steps: (1) a proton is transferred from the lytic water to Asp32′, followed by the nucleophilic addition of the resulting hydroxyl to the carbonyl carbon of the scissile bond, forming a tetrahedral oxyanion intermediate, and (2) a proton is transferred from Asp32 to the peptide nitrogen of the scissile bond, leading to the spontaneous breakage of the scissile bond. The rate-limiting step of this catalytic process is the proton transfer from Asp32 to the peptide nitrogen of the scissile bond, with a free energy of activation of 21.1 kcal/mol. This free energy barrier is close to the experimentally determined free energy of activation (16.3 kcal/mol) calculated from the measured catalytic rate constant (k cat). This mechanistic study provides detailed dynamic and structural information that will facilitate the design of mechanism-based inhibitors for the treatment of HTLV-1-associated diseases.

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“…HTLV-1, HTLV-2, HTLV-3, and HTLV-4 are the four major subtypes of HTLV that have been identified so far. These group of viruses not only cause malignancy but also other inflammatory and immunosuppressive diseases (1,2). HTLVs are enveloped viruses with a diameter ranging from 80 to 100 nm and within the HTLV virions, the reverse transcriptase (RT), integrase, protease viral enzymes, and capsid proteins form complexes with the two covalently bonded genomic RNA strands (3,4).…”

Section: Introductionmentioning

confidence: 99%

“…Among the members of HTLVs, the pathogenic roles of HTLV-1 and HTLV-2 in the human body are well-studied to date compared to HTLV-3 and HTLV-4, and these group of viruses are transmitted through bodily fluids like semen, blood and milk (2). HTLV-1, in particular, is the most life-threatening member of this viral family, causing fatal ATL in approximately 5% of the infected cases that characterizes high blood circulation, lymph node swelling and immunosuppression (7,8).…”

Section: Introductionmentioning

confidence: 99%

Accelerating Cancer Vaccine Development for Human T-Lymphotropic Virus (HTLV) Using a High-Throughput Molecular Dynamics Approach

Moin,

Rani,

Ullah

et al. 2023

Preprint

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Human T-lymphotropic virus (HTLV), a retrovirus belonging to the oncovirus family, has long been linked to be associated with various inflammatory and immunosuppressive disorders. To combat the devastating impact of this virus, our study employed a reverse vaccinology approach to design a multi-epitope-based vaccine targeting the highly virulent subtypes of HTLV. We conducted a comprehensive analysis of the molecular interactions between the vaccine and Toll-like receptors (TLRs), providing valuable insights for future research on preventing and managing HTLV-related diseases and any possible outbreaks. The vaccine was designed by focusing on the envelope glycoprotein gp62, a crucial protein involved in the infectious process and immune mechanisms of HTLV inside the human body. Epitope mapping identified T cell and B cell epitopes with low binding energies, ensuring their immunogenicity and safety. Linkers and adjuvants were incorporated to enhance the vaccine's stability, antigenicity, and immunogenicity. Two vaccine constructs were developed, both exhibiting high antigenicity and conferring safety. Vaccine construct 2 demonstrated expected solubility and structural stability after disulfide engineering. Molecular docking analyses revealed strong binding affinity between the vaccine construct 2 and both TLR2 and TLR4. Molecular dynamics simulations indicated that the TLR2-vaccine complex displayed enhanced stability, compactness, and consistent hydrogen bond formation, suggesting a favorable affinity. Contact analysis, Gibbs free energy landscapes, and DCC analysis further supported the stability of the TLR2-vaccine complex, while DSSP analysis confirmed stable secondary structures. MM-PBSA analysis revealed a more favorable binding affinity of the TLR4-vaccine complex, primarily due to lower electrostatic energy. In conclusion, our study successfully designed a multi-epitope-based vaccine targeting HTLV subtypes and provided valuable insights into the molecular interactions between the vaccine and TLRs. These findings should contribute to the development of effective preventive and treatment approaches against HTLV-related diseases.

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Human T-Lymphotropic Viruses (HTLV)

Cited by 4 publications

References 48 publications

An immunoinformatics and extended molecular dynamics approach for designing a polyvalent vaccine against multiple strains of Human T-lymphotropic virus (HTLV)

An immunoinformatics and extended molecular dynamics approach for designing a polyvalent vaccine against multiple strains of Human T-lymphotropic virus (HTLV)

Catalytic Mechanism of Human T-Cell Leukemia Virus Type 1 Protease Investigated by Combined QM/MM Molecular Dynamics Simulations

Accelerating Cancer Vaccine Development for Human T-Lymphotropic Virus (HTLV) Using a High-Throughput Molecular Dynamics Approach

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