Special Issue "40 Years Anniversary of HTLV-1 Discovery"

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: 15 September 2021.

Special Issue Editor

Prof. Dr. Louis M. Mansky
E-Mail Website
Guest Editor
Institute for Molecular Virology, University of Minnesota, 18-242 Moos Tower, 515 Delaware St. SE, Minneapolis, MN 55455, USA
Interests: human retroviruses; virus assembly; reverse transcription; retroviral diversity and evolution; antiretroviral
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

The discovery of the retroviral reverse transcriptase in 1970 and the subsequent declaration of the “War on Cancer” led to an intense surge of research activity directed towards the identification of human cancer retroviruses. Many cancer researchers abandoned this search, largely due to flawed results caused by a variety of objects. The laboratory of Dr. Robert C. Gallo continued to pursue this goal. Their research involved the development of specific assays along with new cell culture methods, leading to the identification and initial characterization of human T cell leukemia virus type 1 (HTLV-1), which was produced by a T cell line from a lymphoma patient (Poiesz et. al., 1980, Proc. Natl. Acad. Sci. USA 77:7415-7419). This rapidly led to other reports describing the characterization of some of the HTLV-1 proteins, evidence of integrated proviral DNA in infected cells, and serological assays for antibodies indicative of HTLV-1 infection.

Roughly 15 million people are infected with HTLV-1 and many millions with HTLV type 2 (HTLV-2) worldwide. HTLV-1 is associated with the T-lymphocytic malignancy, adult T cell leukemia/lymphoma (ATLL), in about 2% of individuals infected, with another 2–3% developing a neurologic disorder called HTLV-associated myelopathy (HAM). HTLV-2 causes HAM in approximately 1–2% of infected individuals, however does not cause ATLL. HTLV-1 and HTLV-2 have served as highly informative models for the study of the epidemiology and pathogenesis of virus-associated cancers as well as autoimmune conditions such as multiple sclerosis. Two more recently identified members—HTLV-3 and HTLV-4—have been discovered in bushmeat hunters from central Africa, which has further emphasized the unmet need for continual surveillance for emerging new human retroviruses and their capacity to cause disease. The COVID-19 pandemic has highlighted the critical importance of the threats posed by emerging viruses in the human population, which can have catastrophe results if society is not well prepared for such public health crises.

The HTLV-1 oncoprotein Tax-1 is both necessary and sufficient for viral transformation, while Tax-2 (encoded by HTLV-2) does not induce tumors in animal models. The HTLVs encode for other regulatory proteins, including the HTLV-1 basic leucine zipper factor (HBZ), which inhibits Tax-mediated gene expression and is encoded as an anti-sense viral transcript. Another important protein is the HTLV-1 p30II protein, which can act as an agonist of Tax-mediated transcription and serve as a multifunctional repressor of cellular gene expression.

The study of HTLV-1-mediated leukemogenesis remains an important area of investigation. The focus of ongoing research remains centered upon: (i) the Tax effects on cellular transformation; (ii) the consequences of perturbing cell cycle control and genome stability; (iii) the role of HBZ and p30II on viral pathogenesis; (iv) HTLV-1 latency and reactivation; as well as (v) the development of therapeutic approaches. The study of HAM pathogenesis continues to hold promise as a model for neuroimmunologic diseases. New and exciting progress continues to be made in the basic understanding of viral replication of the HTLVs, particularly in virus assembly and particle structure.

The high prevalence rate of HTLV-1 infection among the indigenous population of Central Australia has further emphasized the important public health issues that have yet to be addressed, despite the basic epidemiology of HTLV-1 and HTLV-2 being reasonably well defined – i.e., emergence patterns in new host populations, transmission prevention, improved blood donor screening, and the potential human transmission of HTLV-3 and HTLV-4. Clinical research is particularly needed in order to potentially develop HTLV-1 and HTLV-2 vaccines, as well as the development of treatment options for ATLL and HAM.

The year 2020 marked the 40th anniversary of the discovery of HTLV-1, and this Special Issue highlights the many unmet research needs to be addressed in order to develop effective treatments and a cure for HTLV-1 infection.

Prof. Louis M. Mansky
Guest Editor

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Published Papers (2 papers)

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Research

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Article
An Epitope Platform for Safe and Effective HTLV-1-Immunization: Potential Applications for mRNA and Peptide-Based Vaccines
Viruses 2021, 13(8), 1461; https://doi.org/10.3390/v13081461 - 27 Jul 2021
Viewed by 351
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue 40 Years Anniversary of HTLV-1 Discovery)
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Review

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Review
The Effect of Early Postnatal Nutrition on Human T Cell Leukemia Virus Type 1 Mother-to-Child Transmission: A Systematic Review and Meta-Analysis
Viruses 2021, 13(5), 819; https://doi.org/10.3390/v13050819 - 01 May 2021
Cited by 2 | Viewed by 680
Abstract
The main route of mother-to-child transmission (MTCT) of human T cell leukemia virus type 1 is vertical transmission via breastfeeding. Although the most reliable method for preventing MCTC is exclusive formula feeding (ExFF), short-term breastfeeding (STBF) or frozen–thawed breast milk feeding (FTBMF) has [...] Read more.
The main route of mother-to-child transmission (MTCT) of human T cell leukemia virus type 1 is vertical transmission via breastfeeding. Although the most reliable method for preventing MCTC is exclusive formula feeding (ExFF), short-term breastfeeding (STBF) or frozen–thawed breast milk feeding (FTBMF) has been offered as an alternative method if breastfeeding is strongly desired. The aim of this review was to clarify the pooled risk ratio of MCTC of STBF and FTBMF compared with ExFF. This study was registered with PROSPERO (number 42018087317). A literature search of PubMed, CINAHL, the Cochrane Database, EMBASE, and Japanese databases through September 2018 identified 1979 articles, 10 of which met the inclusion criteria. Finally, 11 articles, including these 10 studies and the report of a recent Japanese national cohort study, were included in the meta-analysis. The pooled relative risks of STBF ≤3 months, STBF ≤6 months, and FTBMF compared with ExFF were 0.72 (95% confidence interval (CI): 0.30–1.77; p = 0.48), 2.91 (95% CI: 1.69–5.03; p = 0.0001), and 1.14 (95% CI: 0.20–6.50; p = 0.88), respectively. This meta-analysis showed no statistical difference in the risk of MTCT between STBF ≤3 months and ExFF, but the risk of MTCT significantly increased in STBF ≤6 months. Full article
(This article belongs to the Special Issue 40 Years Anniversary of HTLV-1 Discovery)
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