Effect of Fc Receptor Genetic Diversity on HIV-1 Disease Pathogenesis

Fc receptor (FcR) genes collectively have copy number and allelic polymorphisms that have been implicated in multiple inflammatory and autoimmune diseases. This variation might also be involved in etiology of infectious diseases. The protective role of Fc-mediated antibody-function in HIV-1 immunity has led to the investigation of specific polymorphisms in FcR genes on acquisition, disease progression, and vaccine efficacy in natural history cohorts. The purpose of this review is not only to explore these known HIV-1 host genetic associations, but also to re-evaluate them in the context of genome-wide data. In the current era of effective anti-retroviral therapy, the potential impact of such variation on post-treatment cohorts cannot go unheeded and is discussed here in the light of current findings. Specific polymorphisms associating with HIV-1 pathogenesis have previously been genotyped by assays that captured only the single-nucleotide polymorphism (SNP) of interest without relative information of neighboring variants. With recent technological advances, variation within these genes can now be characterized using next-generation sequencing, allowing precise annotation of the whole chromosomal region. We herein also discuss updates in the annotation of common FcR variants that have been previously associated with HIV-1 pathogenesis

Analysis of Binding of KIR3DS1*014 to HLA Suggests Distinct Evolutionary History of KIR3DS1

NK cell activity is regulated by the integration of positive and negative signals. One important source of these signals for human NK cells is the killer Ig-like receptor (KIR) family, which includes both members that transduce positive and those that generate negative signals. KIR3DL1 inhibits NK cell activity upon engagement by its ligand HLA-Bw4. The highly homologous KIR3DS1 is an activating receptor, which is implicated in the outcome of a variety of pathological situations. However, unlike KIR3DL1, direct binding of KIR3DS1+ cells to HLA has not been demonstrated. We analyzed four key amino acid differences between KIR3DL1*01502 and KIR3DS1*013 to determine their role in KIR binding to HLA. Single substitutions of these residues dramatically reduced binding by KIR3DL1. In the reciprocal experiment, we found that the rare KIR3DS1 allotype KIR3DS1*014 binds HLA-Bw4 even though it differs from KIR3DS1*013 at only one of these positions (position 138). This reactivity was unexpectedly dependent on residues at other variable positions, as HLA-Bw4 binding was lost in receptors with KIR3DL1-like residues at both positions 199 and 138. These data provide the first evidence, to our knowledge, for the direct binding of KIR3DS1+ cells to HLA-Bw4 and highlight the key role for position 138 in determining ligand specificity of KIR3DS1. They also reveal that KIR3DS1 reactivity and specificity is dictated by complex interactions between the residues in this region, suggesting a unique functional evolution of KIR3DS1 within the activating KIR family

Evaluation of native Trichoderma spp. against pathogens infecting small cardamom

A survey was carried out during 2008-2009 period in the high ranges of Idukki district for isolation and in vitro screening of native Trichoderma spp. against Fusarium oxysporum and Colletotrichum gloeosporioides, pathogens of small cardamom. All the 29 isolates were plated against the two selected plant pathogens in order to test their antagonistic potential and were found to be inhibitive to the growth of F. oxysporum and C. gloeosporioides. In dual cultures, out of the 29 isolates, on seventh day the isolates CT-4, CT-5, CT-10, CT-15, CT-22 and CT-23 showed above 85 per cent reduction on the growth of Fusarium and on tenth day the isolates CT-13, CT-18 and CT-23 showed above 34 per cent reduction on the growth of Colletotrichum. The biomass, spore production, the production potential of siderophore, indole acetic acid (IAA) and hydrogen cyanide (HCN) of these isolates were also assessed. Some of the isolates showed better HCN, IAA and siderophores production. This information can be employed for the exploitation of these biocontrol agents in the high ranges of Idukki district of Kerala for management of the two potential fungal pathogens of small cardamom

Pembuatan Hand Sanitizer dari Daun Sirih dan Jeruk Nipis pada Masyarakat Terdampak Badai Siklon Tropis Seroja di Kelurahan Naibonat Kabupaten Kupang

Kelurahan Naibonat adalah salah satu Kelurahan yang di Kecamatan Kupang Timur Kabupaten Kupang dengan jumlah penduduk mencapai 9.649 jiwa (4.990 laki-laki dan 4.659 perempuan) dengan luas wilayah 22,47 KM2.  Kelurahan Naibonat merupakan salah satu daerah yang terdampak badai siklon tropis seroja kurang lebih 18 jam yang menyebabkan ratusan kepala keluarga mengalami kerusakan tempat tinggal. Berdasarkan fenomena ekstrim tersebut memicu tim Dosen dan mahasiswa Pendidikan Biologi FKIP Undana melakukan Pengabdian Kepada Masyarakat (PKM) di Kelurahan Naibonat kabupaten Kupang. Metode pelaksanaan kegiatan meliputi empat tahapan utama, yaitu sosialisasi, edukasi, demontrasi, dan pembagian produk PKM yaitu hand sanitizer. Bahan alami yang digunakan dalam pembuatan hand sanitizer adalah air rebusan daun sirih dan sari jeruk nipis yang terdapat di sekitar Kabupaten Kupang sebagai antimikroba dan pelembut dalam hand sanitizer. Hasil  kegiatan PKM ini adalah Produk hand sanitizer berbasis bahan alami  yang terbuat dari sari rebusan daun sirih dan air perasan jeruk nipis untuk mencegah infeksi virus corona dan mikroba lainnya, yang langsung dibagikan ke masyarakat peserta PKM sejumlah 49 orang yang hadir pada akhir kegiatan dan juga  mitra sasaran memiliki pengetahuan dan kesadaran serta keterampilan dalam membuat hand sanitizer sendiri dari bahan alam  khususnya dari daun sirih dan air jeruk nipis di rumah masing-masing

Specificity Matters: Unpacking Impact Pathways of Individual Interventions Within Bundled Packages Helps Interpret the Limited Impacts of a Maternal Nutrition Intervention in India

BACKGROUND: To address gaps in coverage and quality of nutrition services, Alive & Thrive (A&T) strengthened the delivery of maternal nutrition interventions through government antenatal care (ANC) services in Uttar Pradesh, India. The impact evaluation of the A&T interventions compared intensive ANC (I-ANC) with standard ANC (S-ANC) areas and found modest impacts on micronutrient supplementation, dietary diversity, and weight-gain monitoring. OBJECTIVES: This study examined intervention-specific program impact pathways (PIPs) and identified reasons for limited impacts of the A&T maternal nutrition intervention package. METHODS: We used mixed methods: frontline worker (FLW) surveys (n = ∼500), counseling observations (n = 407), and qualitative in-depth interviews with FLWs, supervisors, and block-level staff (n = 59). We assessed 7 PIP domains: training and materials, knowledge, supportive supervision, supply chains, data use, service delivery, and counseling. RESULTS: Exposure to training improved in both I-ANC and S-ANC areas with more job aids used in I-ANC compared with S-ANC (90% compared with 70%), but gaps remained for training content and refresher trainings. FLWs\u27 knowledge improvement was higher in I-ANC than S-ANC (22-36 percentage points), but knowledge of micronutrient supplement benefits and recommended foods was insufficient (90%), but supportive supervision was limited by staff vacancies and competing work priorities. Supplies of iron-folic acid and calcium supplements were low in both areas (30-50% stock-outs). Use of monitoring data during review meetings was higher in I-ANC than S-ANC (52% compared with 36%) but was constrained by time, understanding, and data quality. Service provision improved in both I-ANC and S-ANC areas, but counseling on supplement benefits and weight-gain monitoring was low (30-40%). CONCLUSIONS: Systems-strengthening efforts improved maternal nutrition interventions in ANC, but gaps remained. Taking an intervention-specific perspective to the PIP analysis in this package of services was critical to understand how common and specific barriers influenced overall program impact

Multivariate analysis of FcR-mediated NK cell functions identifies unique clustering among humans and rhesus macaques

Rhesus macaques (RMs) are a common pre-clinical model used to test HIV vaccine efficacy and passive immunization strategies. Yet, it remains unclear to what extent the Fc-Fc receptor (FcR) interactions impacting antiviral activities of antibodies in RMs recapitulate those in humans. Here, we evaluated the FcR-related functionality of natural killer cells (NKs) from peripheral blood of uninfected humans and RMs to identify intra- and inter-species variation. NKs were screened for FcγRIIIa (human) and FcγRIII (RM) genotypes (FcγRIII(a)), receptor signaling, and antibody-dependent cellular cytotoxicity (ADCC), the latter mediated by a cocktail of monoclonal IgG1 antibodies with human or RM Fc. FcγRIII(a) genetic polymorphisms alone did not explain differences in NK effector functionality in either species cohort. Using the same parameters, hierarchical clustering separated each species into two clusters. Importantly, in principal components analyses, ADCC magnitude, NK contribution to ADCC, FcγRIII(a) cell-surface expression, and frequency of phosphorylated CD3ζ NK cells all contributed similarly to the first principal component within each species, demonstrating the importance of measuring multiple facets of NK cell function. Although ADCC potency was similar between species, we detected significant differences in frequencies of NK cells and pCD3ζ+ cells, level of cell-surface FcγRIII(a) expression, and NK-mediated ADCC (P<0.001), indicating that a combination of Fc-FcR parameters contribute to overall inter-species functional differences. These data strongly support the importance of multi-parameter analyses of Fc-FcR NK-mediated functions when evaluating efficacy of passive and active immunizations in pre- and clinical trials and identifying correlates of protection. The results also suggest that pre-screening animals for multiple FcR-mediated NK function would ensure even distribution of animals among treatment groups in future preclinical trials

HLA/KIR Restraint of HIV: Surviving the Fittest

Multiple epidemiological studies have demonstrated associations between the human leukocyte antigen (HLA) loci and human immunodeficiency virus (HIV) disease, and more recently the killer cell immunoglobulin-like (KIR) locus has been implicated in differential responses to the virus. Genome-wide association studies have convincingly shown that the HLA class I locus is the most significant host genetic contributor to the variation in HIV control, underscoring a central role for CD8 T cells in resistance to the virus. However, both genetic and functional data indicate that part of the HLA effect on HIV is due to interactions between KIR and HLA genes, also implicating natural killer cells in defense against viral infection and viral expansion prior to initiation of an adaptive response. We review the HLA and KIR associations with HIV disease and the progress that has been made in understanding the mechanisms that explain these associations

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Supplementary data from: "Single cell transcriptomics identifies prothymosin α restriction of HIV-1 in vivo"

Data associated with supplementary figures in "Single cell transcriptomics identifies prothymosin α restriction of HIV-1 in vivo"</p