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

Ezra D Mirvish,Masahiro Shuda

doi:10.3389/fmicb.2016.00676

Abstract

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.

Highlights

20% of human cancers worldwide are associated with infectious agents, including parasites, bacteria, and viruses (Parkin, 2006)
In 12% of cancers, seven different viruses have been causally linked to human oncogenesis (Table 1): Epstein–Barr virus (EBV), hepatitis B virus (HBV), human T-lymphotropic retrovirus type 1 (HTLV-1), high-risk human papillomaviruses (HPV), hepatitis C virus (HCV), Kaposi’s sarcoma herpesvirus (KSHV), and Merkel cell polyomavirus (MCV)
Similar type C particles were identified in MT-1 cells derived from Japanese patients with adult T cell leukemia (ATL), which is known to be caused by HTLV-1 (Hinuma et al, 1981)

Summary

INTRODUCTION

20% of human cancers worldwide are associated with infectious agents, including parasites, bacteria, and viruses (Parkin, 2006). In 12% of cancers, seven different viruses have been causally linked to human oncogenesis (Table 1): Epstein–Barr virus (EBV), hepatitis B virus (HBV), human T-lymphotropic retrovirus type 1 (HTLV-1), high-risk human papillomaviruses (HPV), hepatitis C virus (HCV), Kaposi’s sarcoma herpesvirus (KSHV), and Merkel cell polyomavirus (MCV). Cancers that are related to immunosuppression, for example, are candidates for being caused by tumor viruses (Grulich et al, 2007). During the 20th century, various methods, ranging from the classical electron microscopic observation to the advanced molecular biology techniques, were used to identify cancer-causing viruses. Adult T cell leukemia Cervical carcinoma, head and neck carcinoma, anogenital cancer HCC Kaposi’s sarcoma, primary effusion lymphoma, Castleman’s disease Merkel cell carcinoma. Blumberg et al, 1967 Poiesz et al, 1980 Durst et al, 1983; Boshart et al, 1984 Choo et al, 1989 Chang et al, 1994

METHODS

Immunologic Methods to Detect Viral Antigen

Findings

CONCLUDING REMARKS