Early and transient reverse transcription during primary deltaretroviral infection of sheep

Here we demonstrate that the primary experimental bovine leukemia virus (BLV) infection of sheep displays an early and intense burst of horizontal replicative dissemination of the virus generating frequent RT-associated substitutions that account for 69% of the in vivo BLV genetic variability during the first 8 months of the infection. During this period, evidence has been found of a cell-to-cell passage of a mutated sequence and of a sequence having undergone both RT-associated and somatic mutations. The detection of RT-dependent proviral substitution was restricted to a narrow window encompassing the first 250 days following seroconversion.In contrast to lentiviruses, deltaretroviruses display two time-dependent mechanisms of genetic variation that parallel their two-step nature of replication in vivo. We propose that the early and transient RT-based horizontal replication helps the virus escape the first wave of host immune response whereas somatic-dependent genetic variability during persistent clonal expansion helps infected clones escape the persistent and intense immune pressure that characterizes the chronic phase of deltaretrovirus infection.Retroviruses are unique in that they exist as DNA and/or RNA species. Their polymerases are reverse transcriptases devoid of 3' exonucleolytic activity, and genetic variability is thereby a part of their way of life [1]. Among retroviruses, deltaretroviruses possess an additional mechanism of replication that accompanies an original way of genetic variability. In addition to reverse transcriptase, that generate an error rate in the same range as those of other retroviruses; these lymphotropic viruses encode regulatory proteins that interfere with many host cell pathways including cell cycle, apoptosis and DNA repair [2,3]. This results in the persistent clonal expansion of infected cells and generates a significant level of genetic variability resulting from somatic mutations of the proviral sequence [4-6].Deltaretrovir