Oncogenesis by retroviruses: old and new paradigms.

Retroviruses are associated with a variety of diseases including an array of malignancies, immunodeficiencies and neurological disorders. In particular, studies of oncogenic retroviruses established fundamental principles of modern molecular cancer biology. Studies of avian Rous sarcoma virus (RSV) led to the discovery of the viral oncogene src, and this was followed by the discovery of other viral oncogenes in retroviruses of mammals including rodents, cats, monkeys and so forth. Studies of the viral oncogenes in turn led to the discovery of cellular proto-oncogenes in the host genome; cellular oncogenes have been shown to be activated in a variety of human cancers, including those with no viral involvement. Oncogenic animal retroviruses can be divided into two groups based on their mechanisms of tumourigenesis, acute transforming retroviruses and nonacute retroviruses. Acute transforming retroviruses are typically replication defective and they induce tumours rapidly due to expression of their viral oncogenes. Nonacute retroviruses are replication competent and they induce tumours with longer latencies, by activating cellular proto-oncogenes in the tumour cells; this results from insertion of proviral DNA in the vicinity of the activated proto-oncogene. More recently, human T-cell leukaemia virus type I (HTLV-I) was discovered as an etiological agent of human cancer (adult T-cell leukaemia [ATL]); this virus also encodes regulatory genes some of which are important for its oncogenic potential. Most recently, the retroviral structural protein Envelope (Env) has been shown to be directly involved in oncogenic transformation for certain retroviruses. Env-induced transformation is a new paradigm for retroviral oncogenesis. In this review, we will summarise research on retrovirus oncogenic transformation over the past 100 years since the first published report of an oncogenic virus with particular attention to Env-induced transformation.