Human polyomavirus 7 (HPyV7) is one of 11 HPyVs recently discovered through genomic sequencing technologies. Two lung transplant recipients receiving immunosuppressive therapy developed pruritic, brown plaques on the trunk and extremities showing a distinctive epidermal hyperplasia with virus-laden keratinocytes containing densely packed 36-45-nm icosahedral capsids. Rolling circle amplification and gradient centrifugation testing were positive for encapsidated HPyV7 DNA in skin and peripheral blood specimens from both patients, and HPyV7 early and capsid proteins were abundantly expressed in affected tissues. We describe for the first time that HPyV7 is associated with novel pathogenicity in some immunosuppressed individuals.

Infectious agents have long been suspected as potential causative agents in cutaneous T-cell lymphoma (CTCL). Tissues of patients with CTCL have been evaluated for evidence of infection with a number of agents, including Staphylococcus aureus, retroviruses, and herpesviruses. These studies have failed to reveal a consistent association of CTCL with investigated agents. However, there is substantial evidence suggesting a potential role of a yet unidentified virus in CTCL. This article will review the findings of studies exploring potential roles of infectious agents in CTCL. In addition, we investigated CTCL tissues for evidence of infection with Merkel cell polyomavirus, a novel polyomavirus that was recently discovered as a probable carcinogenic agent in Merkel cell carcinoma. Cutaneous lesions demonstrating mycosis fungoides were stained with a monoclonal antibody against the Merkel cell polyomavirus T antigen, along with appropriate positive and negative controls. Immunohistochemical stains produced negative results in all examined mycosis fungoides specimens. These findings, which suggest a lack of association of CTCL with Merkel cell polyomavirus, add to the current body of knowledge regarding infectious agents and CTCL.

Background Microarray hybridization studies in Sezary Syndrome (SS) have compared T lymphocytes from cutaneous T-cell lymphoma patients to those of normal controls; a major limitation of this design is that significant inherent genetic variability of lymphocyte populations between individuals may produce differences in gene expression unrelated to disease state. Objective The objective of this study was to minimize the heterogeneity of information derived from whole-genome expression analysis and to identify specific genetic differences between highly purified malignant and nonmalignant (control) T cells from the same SS patient. Patients/Methods Peripheral blood mononuclear cells were obtained from a SS patient, stained with anti-T cell receptor-Vβ (TCR-Vβ) antibodies, and sorted by multiparameter flow cytometry. Malignant cells expressed the dominant TCR-Vβ; control T cells lacked the dominant TCR-Vβ but were otherwise phenotypically identical (CD3+ CD4+ CD45RO+). These cell populations were compared using the Illunina Inc. Sentrix Human-6 expression BeadChip system. Results Transcriptome analysis using the J5 test, which was selected for data analysis based on an efficiency analysis of competing statistical methods, showed differential expression of 44 genes between the malignant and nonmalignant cell subsets. Promyelocytic leukemia zinc finger protein (ZBTB16) was the most profoundly upregulated gene in the malignant cell population, while interferon regulatory factor 3 (IRF3) and interferon-induced protein 35 (IFI35), which are important elements of the cellular response to viral infection, were significantly downregulated. Conclusions The results of this study suggest the feasibility of this novel comparative approach to genomic profiling in SS. Using this approach, we identified several differentially expressed genes and pathways not previously described in SS. While these findings require validation in larger studies, they may be important in SS pathogenesis.

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Over 20% of human cancers worldwide are associated with infectious agents, including viruses, bacteria, and parasites. Various methods have been used to identify human tumor viruses, including electron microscopic observations of viral particles, immunologic screening, cDNA library screening, nucleic acid hybridization, consensus PCR, viral DNA array chip, and representational difference analysis. With the Human Genome Project, a large amount of genetic information from humans and other organisms has accumulated over the last decade. Utilizing the available genetic databases, Feng et al. (2007) developed digital transcriptome subtraction (DTS), an in silico method to sequentially subtract human sequences from tissue or cellular transcriptome, and discovered Merkel cell polyomavirus (MCV) from Merkel cell carcinoma. Here, we review the background and methods underlying the human tumor virus discoveries and explain how DTS was developed and used for the discovery of MCV.