Involvement of cutavirus in a subset of patients with cutaneous T-cell lymphoma with an unfavorable outcome

Hashida, Yumiko; Nakajima, Kimiko; Higuchi, Tomonori; Nakai, Kozo; Daibata, Masanori

doi:10.1016/j.jcv.2023.105523

Cited by 5 publications

(9 citation statements)

References 40 publications

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“…13,14 The discovery of CuV in 2016 and its subsequent association with CTCL and its precursor parapsoriasis, have sparked interest in CuV and its role in CTCL. 1,[3][4][5]8,15 In this study, we confirmed these associations and pinpointed the host cells of CuV in CTCL and PP mainly to skin CD4 + T lymphocytes. We also detected spliced viral mRNA in skin, indicating that CuV is actively transcribing in these CTCL and PP tissues.…”

Section: Discussionsupporting

confidence: 82%

“…CTCL is a group of rare malignancies of T cells infiltrating skin, the most common subtypes being MF and Sézary syndrome (SS) 2 . Since the initial discovery of CuV, our group, and others have detected statistically significant associations of CuV DNA in skin biopsies from CTCL/MF lesions compared with those from healthy subjects or other skin lymphomas 3–5 . Furthermore, we have observed that CuV DNA can be detected in the skin for years after acute infection, despite circulating antibodies 3 …”

Section: Introductionmentioning

confidence: 71%

“…Detection of CuV mRNA in PP skin, even if non-spliced, was also confirmed by a Japanese group during the review process of our study, 18 with a CuV-DNA prevalence of 38%, same as they had in CTCL/MF. 5 Expression of mRNA means that the persistent virus is active in the skin, expressing its genes in the nucleus, whereby it may be more likely to affect the cell and tumor microenvironment. This information is important because the role of CuV in PP and in the carcinogenesis of In contrast to CuV, however, DNA of parvovirus B19 (B19V) is known to persist in both skin and other tissue types of also healthy individuals for decades after the initial infection.…”

Section: Discussionmentioning

confidence: 99%

“…other skin lymphomas. [3][4][5] Furthermore, we have observed that CuV DNA can be detected in the skin for years after acute infection, despite circulating antibodies. 3 The exact cause of CTCL remains unknown, but it has been suggested that chronic antigen stimulation could lead to CTCL carcinogenesis.…”

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confidence: 85%

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Prevalence, tropism, and activity of cutavirus in circulating blood lymphocytes, stool, and skin biopsy specimens of patients with cutaneous T‐cell lymphoma and parapsoriasis en plaques

Mohanraj,

Väkevä,

Ranki

et al. 2024

Journal of Medical Virology

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A significant association has been established between a newly emerging human parvovirus, cutavirus (CuV), and cutaneous T‐cell lymphoma/mycosis fungoides (CTCL/MF) and its precursor parapsoriasis en plaques (PP). CTCL is a heterogeneous group of skin malignancies of T cells, the cause of which remains unknown. This study aimed to determine the activity, spread, and cell tropism of the skin‐persistent CuV. CuV DNA was detected in both skin biopsies (6/20, 30%) and peripheral blood mononuclear cells (PBMCs) (4/29, 13.8%) from 49 CTCL/MF or PP patients, while none from 33 patients with any other type of skin disease or healthy subjects harbored CuV DNA. CuV DNA persisted in the skin or PBMCs for up to 15 years, despite circulating CuV‐specific IgG. Spliced CuV mRNA was expressed in skin, indicating viral activity. Also, both of two available stool samples contained encapsidated CuV genomes, suggesting that the patients excrete infectious virus into the environment. Finally, CuV was observed to target circulating and skin‐resident CD4 + T cells and some skin keratinocytes and macrophages. This is especially intriguing as malignant T cells in CTCL develop from CD4 + T cells. Hence, CuV should be further investigated for the overall role it plays in the complex tumor microenvironment of CTCL/MF.

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Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 85%

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Prevalence, tropism, and activity of cutavirus in circulating blood lymphocytes, stool, and skin biopsy specimens of patients with cutaneous T‐cell lymphoma and parapsoriasis en plaques

Mohanraj,

Väkevä,

Ranki

et al. 2024

Journal of Medical Virology

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“…However, some recently published studies produced conflicting results. While Hashida et al found a significant association of CutaV load with MF in a subset of Japanese patients [ 50 ], Bergallo et al failed to detect the virus in 55 Italian patients’ skin specimens [ 51 ]. The current state of the art of research exploring the association of CutaVs with CTCL is summarized in Table 3 .…”

Section: Parvoviruses Associated With the Etiopathogenesis Of Cutaneo...mentioning

confidence: 99%

The Complex Role of Infectious Agents in Human Cutaneous T-Cell Lymphoma Pathogenesis: From Candidate Etiological Factors to Potential Therapeutics

Angelova,

Rommelaere,

Ungerechts

2024

Pathogens

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Cutaneous T-cell lymphoma (CTCL) is a devastating, potentially fatal T-lymphocyte malignancy affecting the skin. Despite all efforts, the etiology of this disease remains unknown. Infectious agents have long been suspected as factors or co-factors in CTCL pathogenesis. This review deals with the panel of bacterial and viral pathogens that have been investigated so far in an attempt to establish a potential link between infection/carriage and CTCL development. A special focus is given to a recently discovered human protoparvovirus, namely the cutavirus (CutaV), which has emerged as a plausible CTCL etiological agent. Available evidence in support of this hypothesis as well as alternative interpretations and uncertainties raised by some conflicting data are discussed. The complexity and multifacetedness of the Parvoviridae family of viruses are illustrated by presenting another protoparvovirus, the rat H-1 parvovirus (H-1PV). H-1PV belongs to the same genus as the CutaV but carries considerable potential for therapeutic applications in cutaneous lymphoma.

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Presence of herpesviruses, parvoviruses, and polyomaviruses in sinonasal lymphoma

Jauhiainen,

Mohanraj,

Perdomo

et al. 2024

Eur Arch Otorhinolaryngol

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Purpose Sinonasal lymphoma (SL) is a rare lymphatic neoplasm of the nasal cavities, paranasal sinuses and nasopharynx. Whereas some risk factors for SL subtypes have been identified, their aetiology is unknown. Along with other predisposing factors, the viral association of lymphomas, such as Epstein-Barr virus (EBV) and Burkitt and Hodgkin lymphomas, is well-established. Modern molecular biology techniques have enabled the discovery of novel human viruses, exemplified by the protoparvovirus cutavirus (CuV), associated with cutaneous T-cell lymphoma. These findings, and the anatomical location of the sinonasal tract with its rich microbiome and infectious agents, justify in-depth studies among SL. Methods We analysed the presence of 20 viruses of Orthoherpesviridae, Parvoviridae, and Polyomaviridae by qPCR in 24 SL tumours. We performed RNAscope in situ hybridisation (RISH) to localize the viruses. Parvovirus-specific IgG was analysed by enzyme immunoassay and targeted next-generation sequencing (NGS) was applied to detect CuV in plasma. Results We detected viral DNA in 15/24 (63%) tumours; nine of EBV, six of human herpesvirus (HHV) -7, four each of HHV-6B and parvovirus B19, two of cytomegalovirus, and one each of CuV and Merkel-cell polyomavirus. We found tumours with up to four viruses per tumour, and localized CuV and EBV DNAs by RISH. Two of the ten plasma samples exhibited CuV IgG, and one plasma sample demonstrated CuV viremia by NGS. Conclusion Viruses were frequent findings in SL. The EBV detection rate was high in diffuse large B-cell lymphoma, and co-detections with other viruses were prevalent.

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Involvement of cutavirus in a subset of patients with cutaneous T-cell lymphoma with an unfavorable outcome

Cited by 5 publications

References 40 publications

Prevalence, tropism, and activity of cutavirus in circulating blood lymphocytes, stool, and skin biopsy specimens of patients with cutaneous T‐cell lymphoma and parapsoriasis en plaques

Prevalence, tropism, and activity of cutavirus in circulating blood lymphocytes, stool, and skin biopsy specimens of patients with cutaneous T‐cell lymphoma and parapsoriasis en plaques

The Complex Role of Infectious Agents in Human Cutaneous T-Cell Lymphoma Pathogenesis: From Candidate Etiological Factors to Potential Therapeutics

Presence of herpesviruses, parvoviruses, and polyomaviruses in sinonasal lymphoma

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