Thursday, December 6, 2012

Viral oncology of retrovirus

Retrovirus has a unique machinery for its replication in the host cells. Most RNA viruses, either ssRNA viruses or dsRNA viruses, replicate their own genetic material and translate to viral proteins to activate numerous biological functions. There is no DNA generated in their life cycles. Distinct from other RNA viruses, however, retrovirus uses its own RNA-dependent reverse transcriptase to synthesis viral DNA, and then integrate to cellular genome to fulfill the central dogma. 

The strategy of retroviral reverse transcription and integration leads to the oncology of retrovirus. There are many oncogenes presented in the host genome, which remains silence (with no transcription and translation of the protein) until viral promoters are integrated in a certain position of the genome, resulting the transcription of the oncogenes. With accordance of Astrin et al, avian leukemia virus (ALV) is proved to have the capability to insert its viral promoters to the cellular genome and activate c-onc (cellular oncogene). This special trait is the major cause of neoplastic formation of ALV (Hayward, 1981)

Nevertheless, as for the majority of retroviral infection, the formation of oncology is not efficient as expected, since the integration of viral promoters will be trade off with the integration and replication of other essential genes of the virus, including gag, pol and env. The virus loses its basic element to try so hard to activate cellular oncogenes. The failure indicates that most retrovirus causes cancer with the evasion of another helper viruses, like the co-infection of hepatitis B virus (HBV) and hepatitis C virus (HCV). Helper virus is necessary for most retroviral oncology, but not for Rous sarcoma virus (RSV). It has an outstanding mechanism to simultaneously maintain the oncology and its efficient replication.

Hayward, W. S. (1981). Activation of a cellular onc gene by promoter insertion in ALV-induced lymphoid leukosis. Nature, 290(5806), 475. doi:10.1038/290475a0

The following figure illustrates how ALV integrates its own promoter to the cellular genome, as a very old but groundbreaking finding in 1981, Nature

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