Viruses have colonized all kingdoms of life, from bacteria to plants, and from insects to humans, but are themselves at the border of the definition of living entities. Their genomic RNA or DNA embedded in protein coats of various degrees of organization and complexity, sometimes containing diverse viral enzymes and/or lipids and proteins of cellular origin, they absolutely require to be inside cells to replicate, renew, and propagate. Hence, together with the transposons and the bacterial plasmids, they represent the ultimate form of parasitism. Some viruses are rapid hijackers of the cell transcriptional and translational machinery, constantly moving from cell to cell within a host, and from host to host within one or several species. Other establish long-term infection of cells and life-long colonization of their hosts, with some DNA viruses and the retroviruses integrating their genes in the chromosomes of their cell targets.

Although many viruses cause severe, sometimes fatal, acute or chronic diseases, others induce few or no harm in their natural hosts. On an evolutionary time scale, life-long interactions of mobile genetic parasites such as retroviruses and transposons with their host have also been instrumental in shaping the genetic make-up of several species, through a process of integration in the germline of their hosts, sometimes providing them with unexpected benefits. One of the most spectacular examples of such beneficial outcome of genetic parasitism concerns the very emergence of our adaptive immune system, that allows us to discriminate between ‘self’ (our body) and ‘non-self’ (microbes and tumors). The capacity of our adaptive immune system to protect us against infections and cancers depends on the generation of several millions of different antigen receptors that are randomly expressed by lymphocytes through a process of somatic genetic recombination. Rag1 and rag2 (recombination-activating genes) are two of our genes whose products allows this somatic recombination process, and are essential for our survival: human newborns with rag loss of function have no lymphocytes and are condemned to die of infections in the absence of bone marrow transplant therapy. What is the evolutionary origin of these rag genes? They seem to have initially belonged to a transposon, being involved in the ‘selfish’ propagation of this genetic parasite in its hosts.1 Around 400 000 000 years ago, this transposon probably become inserted in the germline of one or several common ancestors of the jawed vertebrates, and rag1 and rag2 progressively become involved in the recombination process that gave rise to our adaptive immune system. Thus, in a counterintuitive manner, a retrospectively welcome failure of one of our ancestors to protect itself against a genetic parasite has been instrumental in the emergence of the organ that now protects us against infections. Similar seemingly paradoxical beneficial functions are exerted by endogenous retroviral sequences that have become a significant part of our genome. For example, an envelope glycoprotein encoded by an endogenous defective retrovirus has been reported to play a crucial role in human placenta development, by allowing syncytia formation of the trophoblasts.2 There have been other very different ways in which viruses have been instrumented by humans to become allies in their fight against disease. More than 200 years ago, the intentional use of the vaccinia virus represented the first effective tool of medicine to prevent disease, leading to the eradication of a fatal viral disease, and to the emergence of the concepts of vaccine and immunity. And the ancestral ability of viruses to insert–and express–themselves in host cells has been more recently instrumented in the form of viral (and retroviral) vectors for gene therapy approaches aimed at curing genetic diseases.3

Log in or create a free account to read this content

Gain free access to this article, as well as selected content from this journal and more on nature.com

Access through your institution

or

Sign in or create an account
Continue with Google
Continue with ORCiD