Abstract
Endogenous retrovirus (ERV) genomes integrated into the chromosomal DNA of the host were first detected in chickens and mice as Mendelian determinants of Gag and Env proteins and of the release of infectious virus particles. The presence of ERV was confirmed by DNA hybridization. With complete host genomes available for analysis, we can now see the great extent of viral invasion into the genomes of numerous vertebrate species, including humans. ERVs are found at many loci in host DNA and also in the genomes of large DNA viruses, such as herpesviruses and poxviruses. The evolution of xenotropism and cross-species infection is discussed in the light of the dynamic relationship between exogenous and endogenous retroviruses.
Highlights
Nowadays, the notion that viral genetic sequences are present in host genomes is commonplace [1,2]
Many host genes have been incorporated into large DNA viruses, such as herpesviuses and poxviruses, as well as oncogenebearing retroviruses
The DNA provirus hypothesis involving reverse transcription and integration is generally regarded as a revolutionary paradigm shift, but the science historian Fisher suggests in a recent reappraisal that Temin was thinking—albeit boldly—within the conceptual framework of his time and that the synthesis of DNA from an RNA template did not overturn the ‘central dogma’ of molecular biology [4]
Summary
The notion that viral genetic sequences are present in host genomes is commonplace [1,2]. Reverse transcriptase had not yet been discovered, Howard Temin had recently enunciated his DNA provirus hypothesis [3]. He postulated that RNA tumour viruses made DNA copies which integrated into host chromosomal DNA, analogous to integration of prophage in bacteria. For small DNA tumour viruses, the full replication cycle occurs via non-integrated circular viral genomes, whereas viral integration into host DNA usually leads to abortive. In full confirmation of Temin’s DNA provirus hypothesis, retroviral integration is an obligatory step in replication, whereas non-integrated 2-LTR circles lead to abortive infection. Germ-line integration has not yet been described for DNA tumour viruses, we know that it occasionally occurs with human herpesvirus 6 [9,10]
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