Consequently, some ERVs have been positively selected selleck chemicals and maintained in the host genome throughout evolution. This review will focus on the critical role of ERVs in development of the mammalian placenta and specifically highlight the biological role of sheep JSRV-related endogenous betaretroviruses in conceptus (embryo and associated extraembryonic membranes) development. Endogenous retroviruses

(ERVs) are present in the genome of all vertebrates and are vertically transmitted as stable, inherited Mendelian genes.1 ERVs are thought to arise from ancient infections of the germline of the host by exogenous retroviruses. The obligatory integration step of the retroviral replication cycle allowed, during evolution, the incorporation of the viral genome (provirus) into the host genome. Retrotransposition or re-infection of the germline can generate further insertions augmenting the number of ERVs loci in the genome.2 ERVs have heavily colonized the genome of all animal species; for example, they account for approximately 8–10% of the human genome.3 A complete ERV ‘provirus’ (i.e. the retroviral genome integrated into the host cell genome) shares the same genomic structure of an exogenous retrovirus, which is four viral genes (gag, pro, pol, and env) flanked by

two long terminal repeats (LTRs) (Fig. 1). The gag gene encodes for the major viral structural protein, while pro and pol encode for the viral enzymatic machinery necessary for the viral replication cycle. The env gene encodes for the envelope check details glycoprotein (Env) that is inserted into the lipid bilayer of the exterior membrane to form the viral envelope and mediates entry of the virus into susceptible cells. The LTRs contain enhancer and promoter elements that direct expression of the viral genes. Most ERVs are destined to extinction if their expression brings deleterious consequences for the host. Thus, their persistence in the host genome is the result of a fine balance reached throughout evolution

which usually renders them replication defective because of the accumulation of mutations, deletions, rearrangements, and methylation.1 ERVs are widespread throughout vertebrate genomes.4 Some ERVs are highly related to exogenous retroviruses, including Jaagsiekte sheep retrovirus (JSRV), mouse mammary tumor virus, feline leukemia virus, and avian leukemia virus, which are currently active and infect Phosphatidylethanolamine N-methyltransferase sheep, mice, cats, and chickens, respectively.1 These ERVs are generally referred to as ‘modern’ ERVs, because they integrated into the host genome after speciation and are closely related to exogenous viruses that are still infectious, while most ERVs do not have an exogenous counterpart. Some modern ERVs are still able to produce infectious virus because of the lack of inactivating mutations. Modern ERVs can also have insertionally polymorphic loci, because they are not completely fixed in a particular population and are still undergoing endogenization.