Strategies for Human Tumor Virus Discoveries: From Microscopic Observation to Digital Transcriptome Subtraction.

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.

Human polyomavirus 7-associated pruritic rash and viremia in transplant recipients.

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 in cutaneous T-cell lymphoma.

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.

Cutaneous reactions to epidermal growth factor receptor inhibitors.

Cutaneous toxicities are the most common adverse effects of antineoplastic therapy with epidermal growth factor receptor (EGFR) inhibitors. Skin reactions to this class of agents usually present as papular and/or pustular follicular eruptions developing within two weeks of treatment onset. Other manifestations include generalized xerosis and pruritus, as well as abnormalities of the hair and nails. For most EGFR inhibitors, the incidence and severity of cutaneous toxicity are associated with clinical benefit. At the same time, cutaneous toxic effects may detract substantially from health-related quality of life, leading to interruption, discontinuation or dose reduction of EGFR inhibitor therapy in significantly affected patients. Current recommendations for treatment of EGFR inhibitor-induced eruptions are based primarily on anecdotal evidence from published case series and physicians' own experiences, and include antibiotics, corticosteroids and retinoids. Randomized controlled trials are needed to enable the development of evidence-based paradigms for the treatment of EGFR inhibitor-induced skin eruptions.