Gammaretrovirus Infections in Humans in the Past, Present, and Future: Have We Defeated the Pathogen?

Gammaretroviruses are ubiquitous pathogens, often associated with the induction of neoplasia, especially leukemia, lymphoma, and sarcoma, and with a propensity to target the germline. The latter trait has left extensive evidence of their infectious competence in vertebrate genomes, the human genome being no exception. Despite the continuing activity of gammaretroviruses in mammals, including Old World monkeys, apes, and gibbons, humans have apparently evaded novel infections by the virus class for the past 30 million years or so. Nevertheless, from the 1970s onward, cell culture studies repeatedly discovered gammaretroviral components and/or virus replication in human samples. The last novel 'human' gammaretrovirus, identified in prostate cancer tissue, culminated in the XMRV frenzy of the 2000s. In the end, that discovery was shown to be due to lab contamination with a murine gammaretrovirus. Contamination is also the likely source of the earlier findings. Complementation between genes of partially defective endogenous proviruses could have been another source of the virions observed. However, the capacity of many gammaretroviruses to replicate in human cell lines, as well as the presence of diverse infectious gammaretroviral species in our animal companions, for instance in mice, cats, pigs, monkeys, chickens, and bats, does not make a transmission to humans an improbable scenario. This review will summarize evidence for, or the lack of, gammaretrovirus infections in humans in the past, present, and near future. Aspects linked to the probabilities of novel gammaretrovirus infections in humans, regarding exposure risk in connection to modern lifestyle, geography, diet, and habitat, together with genetic and immune factors, will also be part of the review, as will be the estimated consequences of such novel infections.