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Background Chronic inflammation is prevalent with antiretroviral therapy (ART)-suppressed human immunodeficiency virus (HIV) infection and one immune cell subset putatively driving this phenomenon is TIGIT+ γδ T cells. Methods To elucidate γδ T-cell phenotypic diversity, spectral flow cytometry was performed on blood lymphocytes from individuals of a HIV and aging cohort and data were analyzed using bioinformatic platforms. Plasma inflammatory markers were measured and correlated with γδ T-cell subset frequencies. Results Thirty-nine distinct γδ T-cell subsets were identified (22 Vδ1+, 14 Vδ2+, and 3 Vδ1−Vδ2−Vγ9+) and TIGIT was nearly exclusively found on the Vδ1+CD45RA+CD27− effector populations. People with ART-suppressed HIV infection (PWH) exhibited high frequencies of distinct clusters of Vδ1+ effectors distinguished via CD8, CD16, and CD38 expression. Among Vδ2+ cells, most Vγ9+ (innate-like) clusters were lower in PWH; however, CD27+ subsets were similar in frequency between participants with and without HIV. Comparisons by age revealed lower 'naive' Vδ1+CD45RA+CD27+ cells in older individuals, regardless of HIV status. Plasma inflammatory markers were selectively linked to subsets of Vδ1+ and Vδ2+ cells. Conclusions These results further elucidate γδ T-cell subset complexity and reveal distinct alterations and connections with inflammatory pathways of Vδ1+ effector and Vδ2+ innate-like subsets during ART-suppressed HIV infection. [ABSTRACT FROM AUTHOR]

Intercropping perennial cereal crops with legume species can offer multiple ecosystem functions and agronomic benefits. This study evaluated the forage dry matter yield (FDMY) and the nutritive value of two perennial cereal grain crop species [ACE 1-rye and Kenza, intermediate wheatgrass (IWG)] intercropped with three perennial legume species (alfalfa, white clover, and sainfoin) using alternate- and same-row seeding methods at five different sites in Alberta. The experimental sites were established in June 2022 using a factorial experimental model with eight treatment factors, including perennial monocultures or intercrop with a legume species. One year after establishment in 2023, the forage dry matter yield (FDMY) varied significantly (P < 0.05) across experimental sites, ranging from 228 kgּ·ha-1ּ·yr-1 for the IWG/sainfoin intercrop to 6,833 kgּ·ha-1ּ·yr-1 for the IWG and alfalfa intercrop treatment. Seeding methods (Same or Alternate row) and site location had a significant effect on the FDMY (P = 0.00126), indicating consistent performance in the two cropping systems across diverse environments and site locations. The study assessed eight treatments (cereal-legume combinations) for forage quality performance, of which seven treatments, including RyeClover, Rye-Sainfoin, Wheat-Alfalfa, Wheat-Clover, Wheat-Sainfoin, Wheat mono, and Rye mono, showed significant effects on forage quality factors of crude protein (CP), NDF, NDFD-48, and the Relative Feed Value (RFV). The nutritive value of forage varied across different treatments, with CP content ranging from 6.28% to 18.94% and acid detergent fiber (ADF) content ranging from 10.28% to 40.27%. This variation suggests that the protein and digestibility requirements for livestock consumption are met at different stages. Additionally, the study suggests that intercropping perennial cereal grain crops with legume species using either alternate or the same row seeding methods can lead to consistent forage productivity across different sites. The forages from these intercropping systems exhibit adequate concentrations of CP and total digestible nutrient (TDN), with an average TDN concentration across all sites of approximately 59.3%. This makes them suitable for fulfilling the dietary requirements of beef or dairy cows at various developmental stages. Further research is ongoing to investigate ecosystem functions such as biological nitrogen fixation and water-use efficiency to optimize management practices for sustainable forage production. [ABSTRACT FROM AUTHOR]

Opioid use may impact the HIV-1 reservoir and its reversal from latency. We studied forty-seven virally suppressed people with HIV (PWH) and observed that lower concentration of HIV-1 latency reversal agents (LRA), used in combination with small molecules that did not reverse latency, synergistically increased the magnitude of HIV-1 re-activation ex vivo, regardless of opioid use. This LRA boosting, which combined a Smac mimetic or low-dose protein kinase C agonist with histone deacetylase inhibitors, generated significantly more unspliced HIV-1 transcription than phorbol 12-myristate 13-acetate (PMA) with ionomycin (PMAi), the maximal known HIV-1 reactivator. LRA boosting associated with greater histone acetylation, modulated surface activation-induced markers, and altered T cell production of TNFα, IL-2, and IFNγ. HIV-1 reservoirs in PWH contained unspliced and polyadenylated (polyA) virus mRNA, the ratios of which were greater in resting than total CD4+ T cells and correct to 1:1 with PMAi exposure. We characterized treated suppressed HIV-1 infection as a period of inefficient, not absent, virus transcription. Multiply spliced HIV-1 transcripts and virion production did not consistently increase with LRA boosting, suggesting the presence of a persistent post-transcriptional block. LRA boosting can be leveraged to probe mechanisms of an effective cellular HIV-1 latency reversal program.

The opioid epidemic may impact the HIV-1 reservoir and its reversal from latency in virally suppressed people with HIV (PWH). We studied forty-seven PWH and observed that lowering the concentration of HIV-1 latency reversal agents (LRA), used in combination with small molecules that do not reverse latency, synergistically increases the magnitude of HIV-1 re-activation ex vivo , regardless of opioid use. This LRA boosting, which combines a Smac mimetic or low-dose protein kinase C agonist with histone deacetylase inhibitors, can generate significantly more unspliced HIV-1 transcription than phorbol 12-myristate 13-acetate (PMA) with ionomycin (PMAi), the maximal known HIV-1 reactivator. LRA boosting associated with greater histone acetylation in CD4 + T cells and modulated T cell activation-induced markers and intracellular cytokine production; Smac mimetic-based boosting was less likely to induce immune activation. We found that HIV-1 reservoirs in PWH contain unspliced and polyadenylated (polyA) virus mRNA, the ratios of which are greater in resting than total CD4 + T cells and can correct to 1:1 with PMAi exposure. Latency reversal results in greater fold-change increases to HIV-1 poly(A) mRNA than unspliced message. Multiply spliced HIV-1 transcripts and virion production did not consistently increase with LRA boosting, suggesting the presence of a persistent post-transcriptional block. LRA boosting can be leveraged to probe the mechanisms of an effective cellular HIV-1 latency reversal program.