Recombinant HIV-1 P24 Fragment (CRF01_AE)

Background: HIV Sentinel Surveillance among pregnant women attending antenatal care clinics, ANC-HSS, is used to estimate HIV prevalence among the general population. Despite the declining trend, HIV prevalence among the general population in Karnataka is still higher than the national average (0.22%), with a recent, noticeable stabilization. Demographic analysis on concentrated HIV infection among pregnant women could be potential indicators for targeted HIV interventions among general population as well as and prevention of parent to child transmission (PPTCT). Objectives: To analyse the demographics of HIV-positive pregnant mothers in Karnataka, thereby identifying the most-at-risk populations (MARP) within the general population. Methods: In total, 24800 eligible pregnant women aged 15-49 attending the ANC clinic for the first time during the surveillance period (Jan-Mar, 2017) were enrolled. Demographic data and blood samples were collected, recorded and tested for HIV. Age-specific factors associated with HIV prevalence, besides the demographics of the HIV positive pregnant women, were analysed to identify the MARP for targeted HIV interventions. Results: Comprehensively, none of the demographic factors was significantly associated with HIV prevalence. Nevertheless, analysis of demographics, HIV test history and ART status of HIV-positive pregnant women reveals prominent prevalence patterns. The epidemic was majorly confined within young, less educated, primigravida and rural mothers of low economic status. Conclusion: ANC-HSS is designed to estimate the HIV prevalence among general population at national, state and district levels and is not reflective of the concentrated epidemic confined to MARP. Identifying the disease pattern specific to MARP is essential for effective targeted interventions and disease management.

Macroautophagy/autophagy delivers cytoplasmic cargo to lysosomes for degradation. In yeast, the single Atg8 protein plays a role in the formation of autophagosomes whereas in mammalian cells there are five to seven paralogs, referred to as mammalian Atg8s (mAtg8s: GABARAP, GABARAPL1, GABARAPL2, LC3A, LC3B, LC3B2 and LC3C) with incompletely defined functions. Here we show that a subset of mAtg8s directly control lysosomal biogenesis. This occurs at the level of TFEB, the principal regulator of the lysosomal transcriptional program. mAtg8s promote TFEB's nuclear translocation in response to stimuli such as starvation. GABARAP interacts directly with TFEB, whereas RNA-Seq analyses reveal that knockout of six genes encoding mAtg8s, or a triple knockout of the genes encoding all GABARAPs, diminishes the TFEB transcriptional program. We furthermore show that GABARAPs in cooperation with other proteins, IRGM, a factor implicated in tuberculosis and Crohn disease, and STX17, are required during starvation for optimal inhibition of MTOR, an upstream kinase of TFEB, and activation of the PPP3/calcineurin phosphatase that dephosphorylates TFEB, thus promoting its nuclear translocation. In conclusion, mAtg8s, IRGM and STX17 control lysosomal biogenesis by their combined or individual effects on MTOR, TFEB, and PPP3/calcineurin, independently of their roles in the formation of autophagosomal membranes.