Antiretroviral Therapy in HTLV-1 Infection: An Updated Overview

Marino-Merlo, Francesca; Balestrieri, Emanuela; Matteucci, Claudia; Mastino, Antonio; Grelli, Sandro; Macchi, Beatrice

doi:10.3390/pathogens9050342

Cited by 31 publications

(27 citation statements)

References 58 publications

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“…Ritonavir is the only known HIV PI, which can be applied in the treatment of HTLV infection since it can inhibit NF-κB activation, but it acts on alternative target(s) rather than the viral protease [ 54 ]. Thus, the identification of potent therapeutic PIs against HTLV PRs is still in demand [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

“…There are also some potential molecules, which are used in the therapy or are in clinical trials, especially purine analogs, histone deacetylase inhibitors, or monoclonal antibodies [ 25 ]. Only some anti-HIV agents including the inhibitors of the nucleoside/nucleotide reverse transcriptase and the protease (PR) are considered to be potential anti-HTLV drugs [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

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Biochemical Characterization, Specificity and Inhibition Studies of HTLV-1, HTLV-2, and HTLV-3 Proteases

Kassay

Mótyán

Matúz

et al. 2021

Life

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The human T-lymphotropic viruses (HTLVs) are causative agents of severe diseases including adult T-cell leukemia. Similar to human immunodeficiency viruses (HIVs), the viral protease (PR) plays a crucial role in the viral life-cycle via the processing of the viral polyproteins. Thus, it is a potential target of anti-retroviral therapies. In this study, we performed in vitro comparative analysis of human T-cell leukemia virus type 1, 2, and 3 (HTLV-1, -2, and -3) proteases. Amino acid preferences of S4 to S1′ subsites were studied by using a series of synthetic oligopeptide substrates representing the natural and modified cleavage site sequences of the proteases. Biochemical characteristics of the different PRs were also determined, including catalytic efficiencies and dependence of activity on pH, temperature, and ionic strength. We investigated the effects of different HIV-1 PR inhibitors (atazanavir, darunavir, DMP-323, indinavir, ritonavir, and saquinavir) on enzyme activities, and inhibitory potentials of IB-268 and IB-269 inhibitors that were previously designed against HTLV-1 PR. Comparative biochemical analysis of HTLV-1, -2, and -3 PRs may help understand the characteristic similarities and differences between these enzymes in order to estimate the potential of the appearance of drug-resistance against specific HTLV-1 PR inhibitors.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Biochemical Characterization, Specificity and Inhibition Studies of HTLV-1, HTLV-2, and HTLV-3 Proteases

Kassay

Mótyán

Matúz

et al. 2021

Life

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“…Most infected people, however, remain asymptomatic, highlighting the role of the immune system in the control of infection [ 9 , 10 , 11 ]. Worldwide, more than 20 million subjects are infected by HTLV and, despite advances in treatment, patients with aggressive ATL generally have a poor prognosis [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

HTLV-1 Infection and Pathogenesis: New Insights from Cellular and Animal Models

Forlani

Shallak

Accolla

et al. 2021

IJMS

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Since the discovery of the human T-cell leukemia virus-1 (HTLV-1), cellular and animal models have provided invaluable contributions in the knowledge of viral infection, transmission and progression of HTLV-associated diseases. HTLV-1 is the causative agent of the aggressive adult T-cell leukemia/lymphoma and inflammatory diseases such as the HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). Cell models contribute to defining the role of HTLV proteins, as well as the mechanisms of cell-to-cell transmission of the virus. Otherwise, selected and engineered animal models are currently applied to recapitulate in vivo the HTLV-1 associated pathogenesis and to verify the effectiveness of viral therapy and host immune response. Here we review the current cell models for studying virus–host interaction, cellular restriction factors and cell pathway deregulation mediated by HTLV products. We recapitulate the most effective animal models applied to investigate the pathogenesis of HTLV-1-associated diseases such as transgenic and humanized mice, rabbit and monkey models. Finally, we summarize the studies on STLV and BLV, two closely related HTLV-1 viruses in animals. The most recent anticancer and HAM/TSP therapies are also discussed in view of the most reliable experimental models that may accelerate the translation from the experimental findings to effective therapies in infected patients.

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“…Although HTLV is also an onco-retrovirus, evidence for treating HTLV-associated T cell leukemia with antiretroviral therapy remains limited. Currently, only the combination of interferon (IFN)-α and zidovudine showed some benefits in patients with T cell leukemia, and the underlying mechanism and the antiviral contribution of zidovudine require further investigation (as reviewed by Marino-Merlo et al [9] and Futsch et al [10]). Therefore, the following discussion will be focused on HIV and HERV.…”

Section: Introductionmentioning

confidence: 99%

Contribution of Human Retroviruses to Disease Development—A Focus on the HIV– and HERV–Cancer Relationships and Treatment Strategies

Grandi

Palanivelu

Lin

2020

Viruses

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Animal retroviruses are known for their transforming potential, and this is also true for the ones hosted by humans, which have gathered expanding attention as one of the potent causative agents in various disease, including specific cancer types. For instance, Human T Lymphotropic virus (HTLV) is a well-studied class of oncoviruses causing T cell leukemia, while human immunodeficiency virus (HIV) leads to acquired immunodeficiency syndrome (AIDS), which is linked to a series of defining cancers including Kaposi sarcoma, certain types of non-Hodgkin lymphoma, and cervical cancer. Of note, in addition to these “modern” exogenous retroviruses, our genome harbors a staggering number of human endogenous retroviruses (HERVs). HERVs are the genetic remnants of ancient retroviral germline infection of human ancestors and are typically silenced in normal tissues due to inactivating mutations and sequence loss. While some HERV elements have been appropriated and contribute to human physiological functions, others can be reactivated through epigenetic dysregulations to express retroviral elements and promote carcinogenesis. Conversely, HERV replication intermediates or protein products can also serve as intrinsic pathogen-associated molecular patterns that cause the immune system to interpret it as an exogenous infection, thereby stimulating immune responses against tumors. As such, HERVs have also been targeted as a potential internal strategy to sensitize tumor cells for promising immunotherapies. In this review, we discuss the dynamic role of human retroviruses in cancer development, focusing on HIV and HERVs contribution. We also describe potential treatment strategies, including immunotherapeutic targeting of HERVs, inhibiting DNA methylation to expose HERV signatures, and the use of antiretroviral drugs against HIV and HERVs, which can be employed as prospective anti-cancer modalities.

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Antiretroviral Therapy in HTLV-1 Infection: An Updated Overview

Cited by 31 publications

References 58 publications

Biochemical Characterization, Specificity and Inhibition Studies of HTLV-1, HTLV-2, and HTLV-3 Proteases

Biochemical Characterization, Specificity and Inhibition Studies of HTLV-1, HTLV-2, and HTLV-3 Proteases

HTLV-1 Infection and Pathogenesis: New Insights from Cellular and Animal Models

Contribution of Human Retroviruses to Disease Development—A Focus on the HIV– and HERV–Cancer Relationships and Treatment Strategies

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