Army liposome formulation containing QS-21 render human monocyte-derived macrophages less permissive to HIV-1 infection by upregulating ABOBEC3A.

Monocyte-derived macrophages (MDM) are highly permissive to HIV-1 infection potentially due to the downregulation of innate factors during the differentiation process. The environmental milieu and innate anti-viral factors which are modulated during macrophage differentiation, have been associated with their increased permissiveness to HIV-1 infection. Here, we demonstrate that the Army Liposome Formulation containing MPLA, and QS-21 (ALFQ) activated MDM that are normally permissive to HIV-1 infection to generate a proinflammatory environment and upregulated anti-viral factors notably APOBEC3A. Induction of APOBEC3A by ALFQ decreased permissiveness to HIV-1 infection, while knockdown of APOBEC3A with APOBEC3AsiRNA resulted in a significant loss in the restriction of HIV-1 infectivity. The liposome formulation ALF55, with identical lipid composition but lacking QS-21 had no effect. Furthermore, the capacity of ALFQ to modulate MDM permissiveness to HIV-1 infection was predominantly mediated by large ALFQ liposomes. Our findings highlight a relationship between innate immune activation, proinflammatory milieu, and upregulation of anti-HIV proteins. Induction of these responses can switch the HIV-1 permissive MDM into a more refractory phenotype.

Independent and combined effects of carbohydrate and caffeine ingestion on aerobic cycling performance in the fed state.

The purpose of this study was to examine the independent and combined effects of carbohydrate and caffeine ingestion on performance and various physiological parameters during aerobic cycling (∼1 h). Ten male cyclists (28 ± 9 years, 73 ± 6 kg, 66 ± 9 mL·kg(-1)·min(-1) maximal oxygen consumption) performed 20 min of steady-state (SS) cycling (60% peak power (W(max))) followed by a simulated 20-km time trial (TT) under placebo (PLA), carbohydrate (CHO), caffeine (CAF), and combined CAF-CHO conditions, all of which were performed in the fed state. CAF-CHO improved TT performance by 3.4% ± 2% (84 ± 57 s) compared with PLA (p < 0.05), whereas no differences were detected among CHO, CAF, and PLA. The SS respiratory exchange ratio was elevated in CHO (0.92 ± 0.03), CAF (0.96 ± 0.07), and CAF-CHO (0.95 ± 0.02) compared with PLA (0.89 ± 0.03) (p < 0.05). Post-SS and post-TT blood glucose levels were also elevated in CAF-CHO (88.3 ± 16.7 mg·dL(-1) and 111.2 ± 33.5 mg·dL(-1), respectively) compared with PLA (74.5 ± 9.8 mg·dL(-1) and 85.4 ± 17.6 mg·dL(-1), respectively) (p < 0.05). Treatment conditions did not differentially impact SS pulmonary ventilation, oxygen consumption, heart rate, peak quadriceps muscle strength, rating of perceived exertion, or blood lactate. CAF and CHO improved TT performance when taken together but not independently. Although the present work did not yield any definitive physiological mechanisms for the performance findings, these data suggest that cyclists in the fed state should ingest carbohydrate and caffeine together to improve time trial performance.