Risks linked to endogenous retroviruses for vaccine production: A general overview

Mammalian genomes contain a heavy load of retroelements, which are mobile sequences requiring reverse transcription for their amplification. A significant proportion of these elements is of retroviral origin, with thousands of sequences resembling the integrated form of infectious retroviruses with two LTRs bordering internal regions homologous to the gag, pol, and env genes. These elements, named endogenous retroviruses (ERVs), are thought to be the remnants of ancestral germline infections by active retroviruses, which have thereafter been transmitted in a Mendelian manner. The sequencing of several mammalian genomes has allowed a comprehensive study of their ERVs. They can be grouped according to sequence homologies into 10-100 families per genome, each containing a few to several hundred elements. Strong similarities between ERVs and present-day retroviruses can be inferred from phylogenetic analyses performed on the pol or env genes, suggesting a common history. As a general rule, most ERVs are old and degenerated, with their open reading frames disrupted, but a few proviruses have retained intact genes and the corresponding proteins can thus be expressed. Some elements still contain gag and pol genes that drive the synthesis of viral particles, as well as envelope genes whose product can be incorporated on their cognate or heterologous viral particles. This presentation will review the general properties of endogenous retroviruses, in relation with their possible consequences on vaccine production.