Cutavirus in Cutaneous Malignant Melanoma

Abstract

A novel human protoparvovirus related to human bufavirus and preliminarily named cutavirus has been discovered. We detected cutavirus in a sample of cutaneous malignant melanoma by using viral enrichment and high-throughput sequencing. The role of cutaviruses in cutaneous cancers remains to be investigated.

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

“…Thus far, human protoparvovirus DNA has been detected mainly in diarrheal feces and two studies have shown the presence of CuV DNA in altogether four malignant CTCL skin lesions and in one melanoma [1,6]. Immunosuppressed organ transplant recipients have in general been shown to be at risk for epithelial skin cancers [13].…”

“…In the original publication of CuV discovery, it was detected by PCR in 2/15 CTCL lesions, whereas 10 skin carcinomas, 16 other skin diseases (8 parapsoriasis, 4 eczema and 4 eczematoid dermatitis), and 3 healthy skin samples were all CuV-DNA negative [1]. Furthermore, one out of 10 melanoma skin samples was reported to harbor CuV DNA [6]. Interestingly, we discovered CuV DNA both in non-malignant and malignant skin of three subjects: two transplant recipients had CuV DNA in basal or squamous cell carcinoma tissue and in healthy skin, whereas one CTCL/MF patient had CuV in both early-and late-stage CTCL lesions, in melanoma, atypical moles, benign skin tumors, and lymph nodes, but not in his prostate samples.…”

“…CTCL represents a group of malignancies of mature T cells, for which viral etiology has been long sought but not found [5]. CuV DNA was recently detected also in the cutaneous melanoma of a patient in Denmark [6]. Like other human parvoviruses, CuV induces a humoral immune response; however, with low seroprevalences (0-5.6%) in all countries analyzed [7].…”

Human Protoparvoviruses

“…Skin samples of other cancers ( n = 10) and non-malignant skin biopsies ( n = 19) were all CuV PCR-negative ( Table 3 ). Later on, CuV DNA was detected with NGS in the malignant skin lesions of one melanoma patient in Denmark [ 31 ], while 9 additional melanoma samples were CuV DNA-negative when using both NGS and PCR. The CuV nt sequence from Denmark was 96.5–93.7% identical to the previously published three sequences covering the entire NS1 and VP coding regions ( Table 4 , data calculated for this review, and Figure 1 ).…”

Atomic Resolution Structures of Human Bufaviruses Determined by Cryo-Electron Microscopy

“…Advances in DNA sequencing technology have led to the discovery of several new members of the ssDNA Parvoviridae that infect humans, including human bocaviruses 1 to 4 (HBoV1-HBoV4), cutavirus (CuV), tusavirus (TuV), bufavirus 1 to 3 (BuV1-BuV3), and human parvovirus 4 (PARV4) [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. These viruses are grouped into different genera based on the DNA sequence of their non-structural (NS) proteins [ 8 ].…”