Authors: Enzo Tramontano (Università degli studi di Cagliari, Italy)
Take a look behind the scenes of a recent Future Virology editorial, entitled ‘The emerging field of endogenous retroviruses: understanding their physiological role and contribution to diseases‘ as we ask author Enzo Tramontano (Università degli studi di Cagliari, Italy) about human endogenous retroviruses, whether they could be linked with disease and the future of this field.
What inspired you to write this piece?
I have been asked to write an Editorial for Future Virology and I thought that the topic could be an interesting one since it is a hot and emerging subject that I believe is going to have an impact in the next few years. Indeed, I find that endogenous retroviruses are an amazing area of investigation raising many relevant and intriguing scientific questions that still await answers.
What is the importance of retroviral DNA integration in human evolution?
The answer to this question is not fully understood yet. Retroviral sequences have been proposed to have had a role in shaping primate genome in a number of instances. The most fascinating and known example is represented by syncytins: these retroviral envelope proteins are encoded by different integrated retroviruses that have been independently exapted in different species through a process of convergent evolution, providing placental functions to eutherian mammals – but also other examples are being studied, including a pivotal role of retroviral integrations in the establishment of complex immune networks and development of the main antiviral systems.
Why have human endogenous retroviruses re-emerged as a research interest?
Human endogenous retroviruses have been estimated to represent 8% of the human genome, which is a very high percentage. These sequences of viral origin have been acquired and modified along the millions of years of primate evolution. This clearly raises the question of ‘what are their functions?’. It is, in fact, difficult to imagine that these sequences have been conserved among many species without having had, and still having, some functional roles. In the last decades, with the development of the current and potent bioinformatic tools, it has become possible to investigate them with these new tools to try to answer, at least in part, to this question.
How could these insertions be linked to certain diseases?
This is still also a not fully understood aspect, which surely deserves more investigation. One possibility is that they could be linked to diseases based on their immune-modulatory and/or oncogenic properties, making these sequences multifaceted elements potentially balancing the same biological activities in serving the host physiology and exerting harmful effects. Even the mere presence of retroviral regulatory sequences near to cellular genes could account for their altered modulation, possibly leading to pathological manifestations. Indeed, complex disorders share a general immune and epigenetics dysregulation, both known to strongly and non-specifically modulate endogenous retroviruses expression.
What further work needs to be done to characterize these possible associations?
In my opinion further work is needed to clearly associate the differential expression (positive or negative) of specific loci of retroviral origin with a certain disease. This will allow to identify specific contributing candidates and to evaluate the physiological and/or pathological role/s of these sequences and eventually their coded products. Of note, even in the absence of a direct etiological role, the expression of retroviral sequences in diseased conditions can provide biomarkers and immunological targets for oncolytic therapies.
What work are you hoping to do/ do you have any predictions for the future?
I think that today there is a growing attention on the human endogenous retroviruses and that this is the time in which questions on their possible role in evolution, current physiology of primates and human diseases development can find some first answers. These are amazing questions to me because they show how what can be seen as negative events, such as the introduction of potentially pathogenic viruses in an animal genome, can instead become an opportunity for evolution up to the domestication/use of these viral elements to improve life. I think that this may be a lesson from the past that can be very instructive also for our current everyday life.
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