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IL-2 captured by traditional T cells induces activation of PDE fpsyg.2015.01413 and AC7 downregulation, as a result major to intracellular cAMP degradation. Low intracellular cAMP is related to improved T-cells proliferation and activation. Consequently of these HIV-mediated alterations of regulatory mechanisms, the balance amongst activated T cells and Treg might be broken, compromising the homeostatic finetuned balance from the immune program.mechanisms capable of hindering viral entry, replication and transcription but in addition guaranteeing the immune system homeostasis. Nevertheless, HIV is capable of infecting and abrogating Treg function by inducing the downregulation of crucial molecules critical to allow Treg-dependent suppression. Impairment of Treg immune-modulatory function and induction of hyper-immune activation, supply an immunological situation favorable for viral infection and replication. The fact that HIV may well exert a suppressive impact upon Treg function support us to know that Treg function could be detrimental for HIV fitness and disease progression. This hypothesis implies that the effective part of Treg on preventing immune hyperactivation outweighs the detrimental effect of Treg upon HIV CD4+ and CD8+-specific responses, which has been a matter of controversy in current years. As much as date, it has been extensively described by other people the pros and cons of Treg immunomodulatory mechanisms in HIV-infected patients and its effect upon illness progression. However, the growing evidence of HIV’s direct influence upon the Treg population adds an more layer of complexity taking into consideration the dysregulation of HIV-infected Treg and also the contribution of such alterations towards the illness progression. Understanding the immune-regulatory mechanisms which are impaired or deregulated will facilitate to unveil the rationale behind the immune hyperactivation that hallmarks HIV disease. This can open new avenues to locate potential targets that could restore the immune homeostasis and, hence, decrease the systemic immune activation and exhaustion that figure out the disease progression.AUTHOR CONTRiBUTiONSJL-A, RC-R, and MP have all participated inside the conception, discussion, and elaboration of this critique.CONCLUDiNG ReMARKSRetroviruses, which include HIV, have coexisted with all the human race for millions of years. By that, host species have evolved to guard themselves by unique mechanisms, such as restriction elements, but also by modulating the immune system to attain a fine-tuned response against the virus and also other pathogens. As a consequence, virus counter-evolution results in an evolutionary arms race. This phenomenon is nicely illustrated in Leigh Van Valens’s Red Queen Hypothesis, where two evolutionary systems, such as host/pathogen are continually developing in order to sustain its fitness relative towards the system they are co-evolving with. Within this overview it has been described how Treg exert numerous immune-modulatoryFUNDiNGAll the authors declare that they have no competing journal.pone.0169185 economic interests. This work was supported by grants from Instituto de Salud Carlos III (ISCIII) co-financed by FEDER funds (PI12/00934; PI12/016763; ICI14/00282; PI15/00011; PI15/00923). RC-R is supported by the ISCIII by means of the “Miguel Servet II” program (CPII13/00033) and M P is supported by the Spanish MICINN by means of the Ram y Cajal I3 Program. JL-A is supported by an IISGM pre-doctoral grant.four. Douek DC, purchase Erastin Picker LJ, Koup RA.