HERVs contain all or a subset of the three genes universally present in the genomes of replication-competent retroviruses. The gag (group antigen) gene encodes proteins that in exogenous retroviruses comprise the nucleo-capsid of the virus (major capsid protein, CA) and a matrix layer (matrix, MA). The gag gene is named because antibodies produced against the Gag proteins cross-react with Gag proteins of retroviruses of the same group (species), but not others. The pol gene encodes several enzymes associated with the retrovirus core, including protease (PR), RT, and IN. Exogenous retroviruses are enveloped; virions contain lipid and products of the env gene designated surface (SU) and transmembrane (TM) glycoproteins. Most HERVs contain partial deletions or mutations that disrupt the reading frames of the genes for each structural protein. HERVs also may have deletions in one or both LTRs. The human genome does contain HERVs, however, such as members of the HERV K family, with long open reading frames encoding functional proteins (see Fig. 1). Notably, the W family of HERVs expresses a functional Env, called syncytin, which functions as a fus-ogen during syncytiotrophoblast formation of the placenta . Newly discovered HERV 113 also seems capable of synthesizing gag, pol, and env protein products . Certain HERVs (for example: HERV-K family members) contain accessory genes analogous to those of complex retroviruses, such as HTLV or HIV, that regulate genome expression or replication (see Fig. 1).
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