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The negative strand of the human immunodeficiency virus-1 (HIV-1) proviral genome contains an antisense open reading frame encoding a protein (ASP) with no known homologs. The presence of immune responses to ASP in people living with HIV-1 (PLWH) demonstrates its expression in vivo. Further, the predicted hydrophobicity of ASP is consistent with its association with the plasma membrane and viral envelope. Despite this body of evidence, the role of ASP in HIV-1 replication remains unknown. In this report, we investigated the hypothesis that the presence of ASP on the viral surface enhances HIV-1 entry into target cells. We generated an ASP-knockout replication-competent HIV-1 molecular clone in the NL4-3 background, which we used to perform cell–cell fusion, viral entry, and viral replication assays. Our results suggest that the presence of ASP on the plasma membrane of infected cells and the envelope of HIV-1 virions enhances viral transmission. Overall, our studies provide first evidence that ASP plays a role in the HIV-1 replication cycle. Further investigation into these observations may lead to the identification of new HIV-1 vulnerabilities that may be the target of novel interventions.

Nucleosomes positioned on the HIV-1 5′ long terminal repeat (LTR) regulate sense transcription as well as the establishment and maintenance of latency. A negative-sense promoter (NSP) in the 3′ LTR expresses antisense transcripts with coding and non-coding activities. Previous studies identified cis-acting elements that modulate NSP activity. Here, we used the two chronically infected T cell lines, ACH-2 and J1.1, to investigate epigenetic regulation of NSP activity. We found that histones H3 and H4 are present on the 3′ LTR in both cell lines. Following treatment with histone deacetylase inhibitors (HDACi), the levels of H3K27Ac increased and histone occupancy declined. HDACi treatment also led to increased levels of RNA polymerase II (RNPII) at NSP, and antisense transcription was induced with similar kinetics and to a similar extent as 5′ LTR-driven sense transcription. We also detected H3K9me2 and H3K27me3 on NSP, along with the enzymes responsible for these epigenetic marks, namely G9a and EZH2, respectively. Treatment with their respective inhibitors had little or no effect on RNPII occupancy at the two LTRs, but it induced both sense and antisense transcription. Moreover, the increased expression of antisense transcripts in response to treatment with a panel of eleven latency-reversing agents closely paralleled and was often greater than the effect on sense transcripts. Thus, HIV-1 sense and antisense RNA expression are both regulated via acetylation and methylation of lysine 9 and 27 on histone H3. Since HIV-1 antisense transcripts act as non-coding RNAs promoting epigenetic silencing of the 5′ LTR, our results suggest that the limited efficacy of latency-reversing agents in the context of ‘shock and kill’ cure strategies may be due to concurrent induction of antisense transcripts thwarting their effect on sense transcription.

Modifications to daily sedentary behavior (SB) and participation in moderate-to-vigorous physical activity (MVPA) may provide beneficial results in the prevention and management of mental disorders, such as Major Depressive Disorder (MDD). This cross-sectional research investigated the minimum number of follow-up days needed to reliably estimate the time spent in SB and MVPA from accelerometer data in people with MDD. SB and physical activity (PA) were assessed using an accelerometer, and classified as time spent in SB and in different PA intensities (light—LPA, moderate—MPA, vigorous—VPA, MVPA, or total—TPA). The minimum days of use were calculated using Spearman–Brown analyses, considering only variables with an ICC > 0.8 (cut point-considered acceptable). In the results, 98 people with MDD showed no differences between the days of the week, and an ICC > 0.8 for SB, MPA, and MVPA (for 2-3-4-5-6 vs. 7). Thus, Spearman–Brown analyses were performed considering 2 days (minimum days with ICC > 0.8) and 7 days (maximum days of original test with ICC > 0.8). Our results suggest that a minimum of 3 days of accelerometer use is necessary to reliably estimate the time of SB, MPA, and MVPA. This finding has a significant practical application, allowing data collection using a reduced duration of accelerometer wear. The optimization of time needed in this context permits the utilization of accelerometers among a greater number of individuals, possibly affecting the sample size of MDD patients in research and decreasing acquisition costs in this scientific area.