Project description:Ebolaviruses are known to cause severe hemorrhagic fever in humans. A new ebolavirus species, Bombali orthoebolavirus (BOMV), was recently detected in bats from Sierra Leone, Kenya, Guinea, Mozambique, and Tanzania. No infectious BOMV has been isolated from field samples, but an infectious recombinant BOMV clone (rBOMV) was recently established. To estimate disease potential in humans, we challenged cynomolgus macaques with rBOMV. Macaques exhibit hallmark features of Ebola virus disease, including vascular leak, lymphopenia, neutrophilia, and elevated inflammation markers. Consistent with these hallmarks, we detected rBOMV in multiple target tissues at peak viremia, including the liver, lymph nodes, and adrenal gland. All animals survived challenge and developed robust adaptive immune responses, including strong BOMV-specific IgG and neutralizing antibody titers. These data suggest that BOMV may have an attenuated disease phenotype compared to more pathogenic ebolaviruses such as Ebola, Bundibugyo, Sudan, or Taï Forest and may serve as an important model of resolving Ebola Virus Disease.
Project description:Transcriptome profiling of pyrethroid resistant field populations of Anopheles funestus across Uganda and neighboring Kenya from Uganda and Kenya compared to a susceptible lab strain FANG
Project description:We evaluated transcriptional profiles in peripheral blood mononuclear cells (PBMCs) from 54 pregnant women in Kenya, 19 of whom delivered preterm.
Project description:Genome wide DNA methylation profiling of isolated monocyte samples from healthy Kenyan children, the same children during an episode of acute malaria, healthy Kenyan adults, and healthy adults from the United States. The Illumina Infinium MethylationEPIC BeadChip microarray was used to obtain DNA methylation profiles across approximately 860,000 CpGs in negatively selected monocyte samples. Samples included monocytes from 8 children from western Kenya obtained while healthy and matching samples from the same 8 Kenyan children obtained during an episode of acute uncomplicated Plasmodium falciparum malaria, 8 healthy malaria-immune adults from western Kenya, and 8 healthy malaria-naive adults from the US. Abstract -- Background: Age-related changes in adaptive and innate immune cells have been associated with a decline in effective immunity and chronic, low-grade inflammation. Epigenetic, transcriptional, and functional changes in monocytes occur with aging, though most studies to date have focused on differences between young adults and the elderly in populations with European ancestry; few data exist regarding changes that occur in circulating monocytes during the first few decades of life or in African populations. We analyzed DNA methylation profiles, cytokine production, and inflammatory gene expression profiles in monocytes from young adults and children from western Kenya. Results: We identified several hypo- and hyper-methylated CpG sites in monocytes from Kenyan young adults vs. children that replicated findings in the current literature of differential DNA methylation in monocytes from elderly persons vs. young adults across diverse populations. Differentially methylated CpG sites were also noted in gene regions important to inflammation and innate immune responses. Monocytes from Kenyan young adults vs. children displayed increased production of IL-8, IL-10, and IL-12p70 in response to TLR4 and TLR2/1 stimulation as well as distinct inflammatory gene expression profiles. Conclusions: These findings complement previous reports of age-related methylation changes in isolated monocytes and provide novel insights into the role of age-associated changes in innate immune functions.
Project description:Understanding why some individual resist HIV-1 infection despite continued exposure is an important goal for vaccine development. We compared CD4+ T cell gene expression at baseline in HIV-1 resistant commercial sex-workers from Nairobi, Kenya to HIV-1 high-risk negative (non-resistant) commercial sex-workers using gene expression arrays Experiment Overall Design: CD4+ T cells from both HIV resistant and HIV low-risk negative individuals were isolated from PBMC after 24 hours of culture by negative selection. Total RNA was isolated and gene expression compared using Affymetrix total genome arrays.