scholarly journals An Epitope Platform for Safe and Effective HTLV-1-Immunization: Potential Applications for mRNA and Peptide-Based Vaccines

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1461
Author(s):  
Guglielmo Lucchese ◽  
Hamid Reza Jahantigh ◽  
Leonarda De Benedictis ◽  
Piero Lovreglio ◽  
Angela Stufano
Keyword(s):  
Spastic Paraparesis ◽  
Cross Reactivity ◽  
Human Proteome ◽  
Vast Number ◽  
Human T Cell ◽  
Potential Applications ◽  
Human Proteins ◽  
Window Approach ◽  
Viral Polyprotein

Human T-cell lymphotropic virus type 1 (HTLV-1) infection affects millions of individuals worldwide and can lead to severe leukemia, myelopathy/tropical spastic paraparesis, and numerous other disorders. Pursuing a safe and effective immunotherapeutic approach, we compared the viral polyprotein and the human proteome with a sliding window approach in order to identify oligopeptide sequences unique to the virus. The immunological relevance of the viral unique oligopeptides was assessed by searching them in the immune epitope database (IEDB). We found that HTLV-1 has 15 peptide stretches each consisting of uniquely viral non-human pentapeptides which are ideal candidate for a safe and effective anti-HTLV-1 vaccine. Indeed, experimentally validated HTLV-1 epitopes, as retrieved from the IEDB, contain peptide sequences also present in a vast number of human proteins, thus potentially instituting the basis for cross-reactions. We found a potential for cross-reactivity between the virus and the human proteome and described an epitope platform to be used in order to avoid it, thus obtaining effective, specific, and safe immunization. Potential advantages for mRNA and peptide-based vaccine formulations are discussed.

scholarly journals NO EVIDENCE OF OSTEOPOROSIS IN YOUNG HTLV-1-INFECTED CARRIERS

2014 ◽  
Vol 2 (2) ◽  
Author(s):  
Antonio Carlos Silva Santos ◽  
Ney Boa Sorte ◽  
Carolina Carneiro de Campos ◽  
Sandra Rocha Gadelha ◽  
Maria Fernanda Rios Grassi ◽  
...  
Keyword(s):  
Spastic Paraparesis ◽  
Cross Sectional Study ◽  
Z Score ◽  
Mineral Density ◽  
Aged Patients ◽  
Cross Sectional ◽  
Human T Cell ◽  
Asymptomatic Individuals ◽  
The Relationship

Osteoporosis has been reported among Human T-cell Lymphotropic Virus type 1 (HTLV-1) infected aged patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) diagnosis. However, the association between osteoporosis and HTLV-1 infection remains unclear. This study aimed to evaluate the presence of bone disorders in young HTLV-1 asymptomatic individuals. A cross sectional study was carried out at the HTLV Reference Center in Salvador, Brazil. Forty-seven HTLV-1 infected asymptomatic and 108 healthy subjects aged between 20 to 45 years were included. Biochemical markers of bone metabolism were measured and bone mineral density (BMD) was determined at the femoral neck and at the lumbar spine (L1 -L4). Significant low BMD (Z-score <-1 ) was found in HTLV-1 infected individuals (1.177 ± 0.103) compared to control subjects (1.225 ± 0.146). In logistics regression analysis HTLV-1 infected subjects were more likely to have low BMD (OR = 3.48; 95%CI 1.29- 9.43) adjusted for low education and body mass index (BMI). Osteoporosis (Z-score <-2) was not found among HTLV-1-infected group. In conclusion, our results found a low BMD in patients infected with HTLV-1 compared to uninfected controls. However, osteoporosis was not observed. Further studies should be conducted to evaluate the relationship between HTLV-1-infection and low BMD.

scholarly journals HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread

Viruses ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 152
Author(s):  
Svetlana Kalinichenko ◽  
Dmitriy Komkov ◽  
Dmitriy Mazurov
Keyword(s):  
T Cell ◽  
Spastic Paraparesis ◽  
Latency Period ◽  
Autoimmune Disorder ◽  
Adult T Cell Leukemia ◽  
Modes Of Transmission ◽  
Human T Cell ◽  
Immunodeficiency Syndrome ◽  
Hiv 1

So far, only two retroviruses, human immunodeficiency virus (HIV) (type 1 and 2) and human T-cell lymphotropic virus type 1 (HTLV-1), have been recognized as pathogenic for humans. Both viruses mainly infect CD4+ T lymphocytes. HIV replication induces the apoptosis of CD4 lymphocytes, leading to the development of acquired immunodeficiency syndrome (AIDS). After a long clinical latency period, HTLV-1 can transform lymphocytes, with subsequent uncontrolled proliferation and the manifestation of a disease called adult T-cell leukemia (ATLL). Certain infected patients develop neurological autoimmune disorder called HTLV-1-associated myelopathy, also known as tropical spastic paraparesis (HAM/TSP). Both viruses are transmitted between individuals via blood transfusion, tissue/organ transplantation, breastfeeding, and sexual intercourse. Within the host, these viruses can spread utilizing either cell-free or cell-to-cell modes of transmission. In this review, we discuss the mechanisms and importance of each mode of transmission for the biology of HIV-1 and HTLV-1.

scholarly journals Molecular characterization of human T-cell leukemia virus type 1 gp46 glycoprotein from healthy carriers and tropical spastic paraparesis/HTLV-associated myelopathy infected individuals

Retrovirology ◽  
2014 ◽  
Vol 11 (Suppl 1) ◽  
pp. P83
Author(s):  
Aline CA Mota-Miranda ◽  
Fernanda K Barreto ◽  
Maria FC Amarante ◽  
Everton Baptista ◽  
Joana P Monteiro-Cunha ◽  
...  
Keyword(s):  
T Cell ◽  
Leukemia Virus ◽  
Spastic Paraparesis ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus ◽  
Healthy Carriers

scholarly journals Balance, functional mobility, and fall occurrence in patients with human T-cell lymphotropic virus type-1-associated myelopathy/tropical spastic paraparesis: a cross-sectional study

2018 ◽  
Vol 51 (2) ◽  
pp. 162-167 ◽  
Author(s):  
Erika Pedreira da Fonseca ◽  
Katia Nunes Sá ◽  
Rebeca Freitas Reis Nunes ◽  
Antônio Carlos Ribeiro Junior ◽  
Síntia Freitas Bastos Lira ◽  
...  
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Spastic Paraparesis ◽  
Cross Sectional Study ◽  
Tropical Spastic Paraparesis ◽  
Functional Mobility ◽  
Sectional Study ◽  
Cross Sectional ◽  
Human T Cell

scholarly journals Candidate Polyanionic Microbicides Inhibit Human T-Cell Lymphotropic Virus Type 1 Receptor Interactions, Cell-Free Infection, and Cell-Cell Spread

2008 ◽  
Vol 53 (2) ◽  
pp. 678-687 ◽  
Author(s):  
Daniela Romer ◽  
David W. Brighty ◽  
Cynthia L. Robson ◽  
Quentin J. Sattentau
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Inflammatory Diseases ◽  
Sexual Transmission ◽  
Spastic Paraparesis ◽  
Virus Spread ◽  
Human T Cell ◽  
Cell Cell

ABSTRACT The human T-cell lymphotropic virus type 1 (HTLV-1) is the cause of adult T-cell leukemia and inflammatory diseases including HTLV-1-associated myelopathy/tropical spastic paraparesis. HTLV-1 can be transmitted through sexual contact, mother-to-child transmission, and exposure to contaminated blood. Microbicides are agents that interfere with microbial infectivity at mucous membranes, and candidates are under development for use against sexually transmitted viruses such as human immunodeficiency virus type 1. We previously demonstrated that cell surface polyanionic heparan sulfate proteoglycans bind the HTLV-1 envelope glycoprotein surface subunit gp46, facilitating cell-cell and cell-free virus spread in vitro. We now show, using assays for Env-receptor binding inhibition, Env-induced cell-cell fusion, cell-cell virus spread, and pseudotype HTLV-1 infectivity, that the soluble polyanions PRO 2000 and dextran sulfate are potent inhibitors of HTLV-1 spread in vitro, with PRO 2000 being the more promising candidate. The results of these studies suggest that candidate topical microbicides may be of use in reducing HTLV-1 sexual transmission.

scholarly journals Immunopathogenesis of Human T-Cell Leukemia Virus Type-1-Associated Myelopathy/Tropical Spastic Paraparesis: Recent Perspectives

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Mineki Saito ◽  
Charles R. M. Bangham
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Leukemia Virus ◽  
Spastic Paraparesis ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus

Human T-cell leukemia virus type-1 (HTLV-1) is a replication-competent human retrovirus associated with two distinct types of disease only in a minority of infected individuals: the malignancy known as adult T-cell leukemia (ATL) and a chronic inflammatory central nervous system disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP is a chronic progressive myelopathy characterized by spastic paraparesis, sphincter dysfunction, and mild sensory disturbance in the lower extremities. Although the factors that cause these different manifestations of HTLV-1 infection are not fully understood, accumulating evidence from host population genetics, viral genetics, DNA expression microarrays, and assays of lymphocyte function suggests that complex virus-host interactions and the host immune response play an important role in the pathogenesis of HAM/TSP. Especially, the efficiency of an individual's cytotoxic T-cell (CTL) response to HTLV-1 limits the HTLV-1 proviral load and the risk of HAM/TSP. This paper focuses on the recent advances in HAM/TSP research with the aim to identify the precise mechanisms of disease, in order to develop effective treatment and prevention.

scholarly journals Human T-cell leukaemia virus type 1: parasitism and pathogenesis

2017 ◽  
Vol 372 (1732) ◽  
pp. 20160272 ◽  
Author(s):  
Charles R. M. Bangham ◽  
Masao Matsuoka
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Inflammatory Diseases ◽  
Spastic Paraparesis ◽  
Cell Leukaemia ◽  
Cell Contact ◽  
Leukaemia Virus ◽  
Human T Cell ◽  
Infected Cells

Human T-cell leukaemia virus type 1 (HTLV-1) causes not only adult T-cell leukaemia-lymphoma (ATL), but also inflammatory diseases including HTLV-1-associated myelopathy/tropical spastic paraparesis. HTLV-1 transmits primarily through cell-to-cell contact, and generates abundant infected cells in the host in order to survive and transmit to a new host. The resulting high proviral load is closely associated with the development of ATL and inflammatory diseases. To increase the number of infected cells, HTLV-1 changes the immunophenotype of infected cells, induces proliferation and inhibits apoptosis through the cooperative actions of two viral genes, tax and HTLV-1 bZIP factor ( HBZ ). As a result, infected cells survive, proliferate and infiltrate into the tissues, which is critical for transmission of the virus. Thus, the strategy of this virus is indivisibly linked with its pathogenesis, providing a clue for prevention and treatment of HTLV-1-induced diseases. This article is part of the themed issue ‘Human oncogenic viruses’.

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