Review Lentiviral Vectors and Antiretroviral Intrinsic Immunity

ABSTRACTMulticellular organisms have evolved under relentless attacks from pathogens, and as a consequence havespiked their genomes with numerous genes that serve to thwart these threats, notably through the buildingof the innate and adaptive arms of the immune system. The innate immune system is by far the most ancient,being found as widely as in plants and Drosophila , while adaptive immunity arose with the emergence of car-tilaginous fishes. Innate immunity enters rapidly into the game during the course of an infection and gener-ally involves the recognition by specific cellular receptors of common pathogen-associated patterns to elicitbroad defensive responses, mediated in humans by interferons, macrophages, and natural killer cells, amongstothers. When innate immunity fails to eradicate the infection quickly, adaptive immune responses enter intoplay, to generate exquisitely specific defenses to virtually any pathogen, thanks to a quasi-infinite repertoireof nonself receptors and effectors. A specific form of innate immunity, coined “intrinsic immunity,” completesthis protection by providing a constant, always-on, line of defense, generally through intracellular obstaclesto the replication of pathogens. This component of the immune system has gained much attention as it wasdiscovered that it is a cornerstone of the resistance of mammals against retroviruses. One of these newly dis-covered intracellular molecular weapons, the APOBEC family of proteins, is active against several classes ofretroelements. We present here the current state of knowledge on this rapidly evolving field and discuss im-plications for gene therapy.