Cutavirus DNA in Malignant and Nonmalignant Skin of Cutaneous T-Cell Lymphoma and Organ Transplant Patients but Not of Healthy Adults

Väisänen, Elina; Fu, Yu; Koskenmies, Sari; Fyhrquist, Nanna; Wang, Yilin; Keinonen, Anne; Mäkisalo, Heikki; Väkevä, Liisa; Pitkänen, Sari; Ranki, Annamari; Hedman, Klaus; Söderlund‐Venermo, Maria

doi:10.1093/cid/ciy806

Cited by 27 publications

(28 citation statements)

References 23 publications

(33 reference statements)

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“…Although some studies have reported viruses such as HTLV-1, Epstein-Barr virus, or protoparvoviruses associated with a minority of CTCLs, there has been no infectious agent consistently linked to the disease to date. 18,19 In agreement with those data, no viruses were detected in the 5 CTCLs we investigated here.…”

Section: Resultssupporting

confidence: 92%

Comprehensive metagenomic analysis of blastic plasmacytoid dendritic cell neoplasm

et al. 2020

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Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a hematologic malignancy believed to originate from plasmacytoid dendritic cells (pDCs), the immune cells responsible for producing type 1 interferons during infection. Nearly all patients with BPDCN have prominent skin involvement, with cutaneous infiltration occupying the dermis and subcutis. One half of patients present with BPDCN cells only in the skin, with no evidence of disease elsewhere. Because normal pDCs are rare or absent in cutaneous sites, and they only traffic to the skin after activation by pathogen or inflammation, our aim was to determine if a microorganism is associated with BPDCN. We performed RNA sequencing in BPDCN skin and bone marrow, with cutaneous T-cell lymphoma (CTCL) and normal skin as controls. GATK-PathSeq was used to identify known microbial sequences. Bacterial reads in BPDCN skin were components of normal flora and did not distinguish BPDCN from controls. We then developed a new computational tool, virID (Viral Identification and Discovery; https://github.com/jnoms/virID), for identification of microbial-associated reads remaining unassigned after GATK-PathSeq. We found no evidence for a known or novel virus in BPDCN skin or bone marrow, despite confirming that virID could identify Merkel cell polyomavirus in Merkel cell carcinoma, human papillomavirus in head and neck squamous cell carcinoma, and Kaposi’s sarcoma herpesvirus in Kaposi’s sarcoma in a blinded fashion. Thus, at the level of sensitivity used here, we found no clear pathogen linked to BPDCN.

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Section: Resultssupporting

confidence: 92%

Comprehensive metagenomic analysis of blastic plasmacytoid dendritic cell neoplasm

et al. 2020

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“…BuV, TuV and CuV are protoparvoviruses discovered in pediatric diarrheal stool samples and CuV was additionally found in skin lesions of cutaneous T-cell lymphoma (CTCL) [15, 16]. It was later detected in both healthy and malignant skin of CTCL and immunosuppressed organ transplant patients, but not in skin of healthy adults [10]. Parvoviruses in general are not considered directly oncogenic like the polyomaviruses.…”

Section: Discussionmentioning

confidence: 99%

“…A multiplex real-time qPCR was used for the detection of the three human protoparvoviruses, with primers located in the NS1 region of BuV and the VP2 region of TuV and CuV, as described [10].…”

Section: Methodsmentioning

confidence: 99%

Newly detected DNA viruses in juvenile nasopharyngeal angiofibroma (JNA) and oral and oropharyngeal squamous cell carcinoma (OSCC/OPSCC)

Dickinson

Silén

et al. 2018

Eur Arch Otorhinolaryngol

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Purpose Approximately 20% of cancers are estimated to have a viral etiology. We aimed to investigate whether DNA of 8 human parvoviruses [bocavirus 1–4 (HBoV1–4), parvovirus B19 (B19V), protoparvoviruses (bufa-, tusa-, and cutavirus)] and 13 human polyomaviruses (HPyV) can be detected in oropharyngeal and oral cavity squamous cell carcinoma (OPSCC/OSCC), and in juvenile nasopharyngeal angiofibroma (JNA) tissue samples. Methods Fresh samples of seven JNA tissues and ten paired tissues of OSCC/OPSCC tumor and adjacent healthy tissues were collected. DNA extraction and real-time PCRs were performed to detect HBoV1-4, B19V, bufa- tusa- and cutavirus, and HPyV genomes. Results JNA specimens were negative for all parvoviruses tested, whereas one JNA sample was Merkel cell polyomavirus (MCPyV) DNA positive. The OSCC/OPSCC samples were negative for the human protoparvoviruses, HBoV1-4, and all human polyomaviruses, except for one patient that was MCPyV DNA positive in both healthy and tumor tissues. Seven OSCC/OPSCC patients were positive for B19V DNA, three of them in both healthy and cancerous tissues and three in only healthy tissues. Three of the B19V DNA-positive patients harbored viral genotype 1, three genotype 2, and one genotype 3B. Conclusions These are the first reports of MCPyV and B19V DNA being detected in JNA and OPSCC. The significance of viral DNA positivity is unclear. B19V DNA is known to remain in the tissues lifelong, however, it is of interest that there are some patients with B19 DNA in healthy tissue, but not in the corresponding cancer tissue.

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“…In 2016, CuV was found in human fecal samples and cutaneous T-cell lymphomas (CTCL) [5,11]. While CuV DNA was found in skin biopsies from~5% of German and 16% of Finnish patients with CTCL [16,17], it was absent in healthy patients, providing a statistically significant association to CTCL [17]. It has been infrequently detected also in malignant skin melanomas and carcinomas [11,17,18].…”

Section: Introductionmentioning

confidence: 99%

“…While CuV DNA was found in skin biopsies from~5% of German and 16% of Finnish patients with CTCL [16,17], it was absent in healthy patients, providing a statistically significant association to CTCL [17]. It has been infrequently detected also in malignant skin melanomas and carcinomas [11,17,18]. Recently, a study for BuV, CuV, and TuV found low prevalences of BuV IgGs in adults in Finland (~2%) and the United States (~4%), but high prevalences in Iraq (~85%), Iran (~56%), and Kenya (~72%), whereas the CuV IgG prevalences were low (0%-6%), and TuV IgGs undetected in the cohorts tested [14].…”

Section: Introductionmentioning

confidence: 99%

Structural Characterization of Cuta- and Tusavirus: Insight into Protoparvoviruses Capsid Morphology

Mietzsch

McKenna

Väisänen

et al. 2020

Viruses

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Several members of the Protoparvovirus genus, capable of infecting humans, have been recently discovered, including cutavirus (CuV) and tusavirus (TuV). To begin the characterization of these viruses, we have used cryo-electron microscopy and image reconstruction to determine their capsid structures to ~2.9 Å resolution, and glycan array and cell-based assays to identify glycans utilized for cellular entry. Structural comparisons show that the CuV and TuV capsids share common features with other parvoviruses, including an eight-stranded anti-parallel β-barrel, depressions at the icosahedral 2-fold and surrounding the 5-fold axes, and a channel at the 5-fold axes. However, the viruses exhibit significant topological differences in their viral protein surface loops. These result in three separated 3-fold protrusions, similar to the bufaviruses also infecting humans, suggesting a host-driven structure evolution. The surface loops contain residues involved in receptor binding, cellular trafficking, and antigenic reactivity in other parvoviruses. In addition, terminal sialic acid was identified as the glycan potentially utilized by both CuV and TuV for cellular entry, with TuV showing additional recognition of poly-sialic acid and sialylated Lewis X (sLeXLeXLeX) motifs reported to be upregulated in neurotropic and cancer cells, respectively. These structures provide a platform for annotating the cellular interactions of these human pathogens.

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Cutavirus DNA in Malignant and Nonmalignant Skin of Cutaneous T-Cell Lymphoma and Organ Transplant Patients but Not of Healthy Adults

Abstract: Our results suggest that dermal CuV DNA carriage is associated with CTCL. Any putative roles of CuV in the carcinogenesis must be determined in forthcoming studies.

Cited by 27 publications

References 23 publications

Comprehensive metagenomic analysis of blastic plasmacytoid dendritic cell neoplasm

Comprehensive metagenomic analysis of blastic plasmacytoid dendritic cell neoplasm

Newly detected DNA viruses in juvenile nasopharyngeal angiofibroma (JNA) and oral and oropharyngeal squamous cell carcinoma (OSCC/OPSCC)

Structural Characterization of Cuta- and Tusavirus: Insight into Protoparvoviruses Capsid Morphology

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