Adenosine pathway is associated with the control of immune activation and inflammation in nonprogressive SIV infection (VIR1P.1009)

Abstract

Abstract Adenosine (ADO) is associated with immunosuppression in multiple diseases, yet its role in modulating immune activation/inflammation (IA/INFL) in HIV-1/SIV infection is unclear. We compared changes in ADO pathway-associated markers between African green monkeys (AGMs) that control SIV-related IA/INFL and pigtailed macaques (PTMs) that exhibit IA/INFL associated with AIDS progression. CD39/CD73 and CD26 (which promote ADO production or breakdown to inosine) were assessed by flow cytometry on T cells from blood, lymph nodes (LNs) and intestine of AGMs and PTMs pre and post SIV infection. ADO was measured by mass spectrometry in frozen tissues. Baseline CD39/CD73 expression on Tregs from LNs and intestine were intrinsically high in AGMs and remained high throughout SIV infection. CD26 and inosine did not change in AGMs. In the gut, basal ADO was high in AGMs and further increased early after infection. Conversely, in PTMs, CD26 expression dramatically increased in the gut early in infection, a change associated with increased inosine. CD39/CD73 only increased during late infection in PTMs. Our results suggest a key role for ADO in the control of IA/INFL in nonprogressive SIV infections and that ADO production may be counteracted by the early increase of CD26 in pathogenic HIV/SIV. Furthermore, changes of ADO levels predominately occur in the gut rather than in blood or LNs, suggesting that future studies of the ADO pathway should focus on mucosal sites of viral replication.