Oncogenesis by retroviruses: old and new paradigms

Abstract

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.

Extracellular vesicles and viruses: Are they close relatives?

“…Therefore, density gradients, which are often used to separate EVs from contaminating protein aggregates on the basis of differences in buoyant densities (40), are not always reliable for separation of EVs from viral particles. Similar technical hurdles were also experienced at the early stages of retrovirus research, when there were long-lasting disagreements and controversies regarding replication-incompetent oncoviral particles causing cancer and their dependence on competent helper viruses for propagation (41). In those early days, electron microscopists observed that ultracentrifuged viruses copelleted with other 100-nmsized membrane-enclosed particles.…”

Roles of HTLV-1 Tax in Leukemogenesis of Human T-Cells

“…Before the discovery of HTLV-1, many oncogenic retroviruses have been found, which induce malignant tumors in animals such as avian and rodent (Maeda et al, 2008). Most animal oncogenic retroviruses carry oncogenes, but they are totally different from the HTLV-1 oncogene for Tax1.…”

Identification of avian leukosis virus subgroup J-associated acutely transforming viruses carrying the v-src oncogene in layer chickens

“…ALV, a member of the genus Alpharetrovirus of the family Retroviridae, can also acquire cellular oncogenes by recombination events during the infection process, producing ATVs with the ability to induce transformation in some specific types of cultured cells and to rapidly induce tumour formation in chickens within 2 weeks (Maeda et al, 2008;Vogt, 2012). To date, dozens of naturally occurring ATVs coding for different viral oncogenes -such as src, fps, myc, myb, jun and ros -have been isolated (Martin, 2001;Vogt, 2012;Wang & Hanafusa, 1988).…”

“…Some ALV strains can obtain cellular oncogenes (c-onc) from host cells by homologous recombination events during infection to become 'acutely transforming viruses' (ATVs), which have the ability to rapidly induce tumour formation in chickens over a period of only a few weeks and can transform some specific cell types in vitro (Maeda et al, 2008). However, most ATVs are replication defective and can replicate only when replication-competent viruses are present to serve as 'helper viruses'.…”