In silico analysis of transcription binding site motifs in endogenous and exogenous retroviruses emphasizes their conservation

Abstract

LTRs flanking the proviral genome in retroviruses are functionally divided into three regions: U3, R and U5. Transcription starts in the first nucleotide of the 5’ R and the region just upstream (5’ U3) contains sites which bind cellular factors and trigger transcription, known as TBS. Retroviruses may become endogenous when they infect germ cells, being transmitted throughout generations. In this review we have used the algorithm ALGGEN to analyze the presence of TBS in the U3 region of both endogenous and exogenous retroviruses. Exogenous retroviruses have included different gammaretroviruses (gibbon ape leukemia virus, GALV; murine leukemia virus, MuLV; koala retrovirus, KoRV and feline leukemia virus, FeLV). Endogenous retroviruses studied were related to FeLV (enFeLV). The most abundant TBS found were related to the immune response (adaptive and innate). Many TBS were arranged in clusters combining six or more overlapping sites, and polymorphisms mostly occurred outside the TBS. The number of TBS was similar in most LTRs analyzed. The analysis of TBS may explain the pathogenesis of each viral type. The high degree of conservation of TBS in endogenous sequences supports their importance.