Seroprevalence of HHV-8, CMV, and EBV among the general population in Ghana, West Africa

<p>Abstract</p> <p>Background</p> <p>Human herpesvirus 8 (HHV-8), cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are prevalent in Africa, but less common elsewhere and the modes of transmission are still subject to debate. Generally, they rarely cause disease in the immunocompetent host but are highly oncogenic when associated with immunosuppression. Although the high prevalence of HHV-8, CMV and EBV has been well documented in Africa, such data are sparse from Ghana.</p> <p>Methods</p> <p>Serum samples from 3275 HIV-seronegative healthy blood donors and 250 HIV-AIDS patients were tested for antibodies specific for HHV-8, CMV and EBV by IgG ELISA assays. Differences in seropositivity rates by gender and age were evaluated using the Chi-square test with Yates correction.</p> <p>Results</p> <p>Of the 3275 HIV-seronegative healthy blood donors tested, 2573 (78.6%) were males and 702 (21.4%) were females, with ages ranging from 18 to 65 years (median 32.6; mean 31.2; mode 30). Of the 250 HIV-AIDS patients tested, 140 (56%) were males and 110 (44%) were females, with ages ranging from 17 to 64 years (median 30.8; mean 30.3; mode 28). Among the HIV-seronegative healthy blood donors, overall seroprevalence of HHV-8, CMV and EBV was 23.7%, 77.6% and 20.0%, respectively. Among the HIV-AIDS patients, overall seroprevalence of HHV-8, CMV and EBV was 65.6%, 59.2% and 87.2%, respectively. The seroprevalence of HHV-8 (p < 0.005) and EBV (p < 0.001) was statistically significantly higher in HIV-AIDS patients compared to HIV-seronegative healthy blood donors. There was no statistically significant difference (p = 0.24) between CMV seroprevalence in HIV-AIDS patients and HIV-seronegative healthy blood donors. Age and gender were not independent determinants (p > 0.05) for all three infections among HIV-seronegative healthy blood donors and HIV-AIDS patients in Ghana.</p> <p>Conclusion</p> <p>The results presented herein indicate that HHV-8, CMV and EBV infections are hyperendemic in both HIV-seronegative and HIV-seropositive Ghanaians, and suggest primarily a horizontal route of transmission of these three viral infections in Ghana.</p

Immune Reconstitution During the First Year of Antiretroviral Therapy of HIV-1-Infected Adults in Rural Burkina Faso

There are no data on the outcome of highly active antiretroviral therapy (HAART) in HIV-infected adults in rural Burkina Faso. We therefore assessed CD4+ T-cell counts and HIV-1 plasma viral load (VL), the proportion of naive T-cells (co-expressing CCR7 and CD45RA) and T-cell activation (expression of CD95 or CD38) in 61 previously untreated adult patients from Nouna, Burkina Faso, at baseline and 2 weeks, 1, 3, 6, 9 and 12 months after starting therapy. Median CD4+ T-cell counts increased from 174 (10th-90th percentile: 33-314) cells/µl at baseline to 300 (114- 505) cells/µl after 3 months and 360 (169-562) cells/µl after 12 months of HAART. Median VL decreased from 5.8 (4.6- 6.6) log10 copies/ml at baseline to 1.6 (1.6-2.3) log10 copies/ml after 12 months. Early CD4+ T-cell recovery was accompanied by a reduction of the expression levels of CD95 and CD38 on T-cells. Out of 42 patients with complete virological follow-up under HAART, 19 (45%) achieved concordant good immunological (gain of ≥100 CD4+ T-cells/µl above baseline) and virological (undetectable VL) responses after 12 months of treatment (intention-to-treat analysis). Neither a decreased expression of the T-cell activation markers CD38 and CD95, nor an increase in the percentage of naive T-cells reliably predicted good virological treatment responses in patients with good CD4+ T-cell reconstitution. Repeated measurement of CD4+ T-cell counts during HAART remains the most important parameter for immunologic monitoring. Substitution of repeated VL testing by determination of T-cell activation levels (e.g., CD38 expression on CD8+ T-cells) should be applied with caution

GLRB allelic variation associated with agoraphobic cognitions, increased startle response and fear network activation : a potential neurogenetic pathway to panic disorder

The molecular genetics of panic disorder (PD) with and without agoraphobia (AG) are still largely unknown and progress is hampered by small sample sizes. We therefore performed a genome-wide association study with a dimensional, PD/AG - related anxiety phenotype based on the Agoraphobia Cognition Questionnaire (ACQ) in a sample of 1,370 healthy German volunteers of the CRC TRR58 MEGA study wave 1. A genome-wide significant association was found between ACQ and single non-coding nucleotide variants of the GLRB gene (rs78726293, p=3.3x10-8; rs191260602, p=3.9x10-8). We followed up on this finding in a larger dimensional ACQ sample (N=2,547) and in independent samples with a dichotomous AG phenotype based on the Symptoms Checklist (SCL-90; N=3,845) and a case control sample with the categorical phenotype PD/AG (Ncombined =1,012) obtaining highly significant p-values also for GLRB single nucleotide variants rs17035816 (p=3.8x10-4) and rs7688285 (p=7.6x10-5). GLRB gene expression was found to be modulated by rs7688285 in brain tissue as well as cell culture. Analyses of intermediate PD/AG phenotypes demonstrated increased startle reflex and increased fear network as well as general sensory activation by GLRB risk gene variants rs78726293, rs191260602, rs17035816 and rs7688285. Partial Glrb knockout-mice demonstrated an agoraphobic phenotype. In conjunction withthe clinical observation that rare coding GLRB gene mutations are associated with the neurological disorder hyperekplexia characterized by a generalized startle reaction and agoraphobic behavior, our data provide evidence that non-coding, though functional GLRB gene polymorphisms may predispose to PD by increasing startle response and agoraphobic cognitions.PostprintPeer reviewe

Transcriptome Analysis in Hybrid Plants using Platinum Genomes

Heterosis refers to the deviation of the F1 progeny from the phenotypic mean of the parental plants, espe- cially in cases where both parents are inbred and homozygous throughout the genome. When comparing certain traits of a F1 hybrid to the corresponding parental plants one can compare the performance of the hybrid to (1) the midparent value (MPV), which refers to the mean of both parental plants for the given trait. Furthermore the F1 hybrid can be compared to (2) the best-parent value (BPV), referring to the value of the superior parental plant. Mainly three genetic models, explaining heterosis have been proposed. However, there is no consensus about the diversity of molecular principles of heterosis. Recent studies suggested structural genome variation, such as copy-number variation (CNV) as well as presence absence variation (PAV), among maize inbred lines, underlying complementary contributions of genes from both parents as an important factor (Springer et al. 2009). Gene expression with regard to heterosis has been analyzed in several plants includingA. thaliana (Alonso-Peral et al. 2017). How- ever, the majority of these studies relied either on microarray data, which are limited to transcripts present on the chip, or on RNA-seq data that have been processed using a single reference genome, thus not accounting for structural variation among different genotypes (accessions). We now have access to high quality full length genome sequences of different A. thaliana accessions. Two of these accessions have been used in a reciprocal crossing. The root and shoot transcriptomes of F1 hybrids as well as from the corresponding parental plants have been short read sequenced. RNA-seq reads have been processed using either one parental genome as a reference or a trans-reference genome, containing full length genome sequences of both parental plants and accounting for orthologous assignment. DESeq2 has been used to detect transcripts with non parental expression patterns (below or above MPV) in the F1 hybrid plants. When using a single reference genome we found various transposable elements among the differentially expressed genes (p < 0.01). However, whole genome alignment data among parental plants indicate that many of these are due to a reference bias. Here we present a way of how to process a double reference genome in order to improve the analysis of hybrid transcriptomes regarding heterosis

The improved genome of the nematode Parapristionchus giblindavisi provides insights into lineage-specific gene family evolution

Nematodes such as Caenorhabditis elegans and Pristionchus pacificus are extremely successful model organisms for comparative biology. Several studies have shown that phenotypic novelty but also conserved processes are controlled by taxon-restricted genes. To trace back the evolution of such new or rapidly evolving genes, a robust phylogenomic framework is indispensable. Here, we present an improved version of the genome of Parapristionchus giblindavisi which is the only known member of the sister group of Pristionchus. Relative to the previous short read assembly, the new genome is based on long reads and displays higher levels of contiguity, completeness, and correctness. Specifically, the number of contigs dropped from over 7303 to 735 resulting in an N50 increase from 112 kb to 791 kb. We made use of the new genome to revisit the evolution of multiple gene families. This revealed Pristionchus-specific expansions of several environmentally responsive gene families and a Pristionchus-specific loss of the de novo purine biosynthesis pathway. Focusing on the evolution of sulfatases and sulfotransferases, which control the mouth form plasticity in P. pacificus, reveals differences in copy number and genomic configurations between the genera Pristionchus and Parapristionchus. Altogether, this demonstrates the utility of the P. giblindavisi genome to date and polarize lineage-specific patterns

Linking resistance and effector genes in the Arabidopsis-Hyaloperonospora pathosystem

The oomycete pathogen Hyaloperonospora arabidopsidis specifically infects a single host, Arabidopsis thaliana, pointing to a strong co-evolutionary relationship. This pathogen secretes effectors into the host cells that are able to manipulate the plant immune network, promoting successful infection. When recognized by the host immune system, though, they confer host resistance in the form of effector-triggered immunity (Coates & Beynon, 2010; Polonio et al., 2020). We have collected and whole-genome sequenced over one hundred new pathogen isolates from much of the European range of Arabidopsis thaliana and discovered allelic diversity within the pathogen effector genes. At the ATR1 locus, we found over 50 alleles, at least some of which might be recognized by different alleles at the host RPP1 locus. RPP1 allelic variation has been deduced from long-read genome >assemblies of A. thaliana accessions. Ongoing experiments seek to understand the functional differences of ATR1 variants on recognition by the host, investigating both different Arabidopsis thaliana accessions and heterologous expression in combination with RPP1 alleles

Homozygosity at its Limit: Inbreeding Depression in Wild Arabidopsis arenosa Populations

New combinations of genetic material brought together through hybridization can lead to unfit offspring as a result of outbreeding or inbreeding depression. In selfing plants such as Arabidopsis thaliana, outbreeding depression is typically the result of pairwise deleterious epistatic interactions between two alleles that can geographically co-occur. What remains elusive is how often alleles resulting in genetic incompatibilities co-occur in natural populations of outcrossing plant species. To address this question, we screened over two thousand five hundred wild Arabidopsis arenosa hybrid plants in search for potential genetic mismatches. We show that although abnormal deleterious phenotypes are common, the transcriptional profiles of these abnormal A. arenosa plants differ substantially from those seen in incompatible A. thaliana hybrids. The abnormal hybrid phenotypes in A. arenosa had different underlying genetic architectures, yet a repeated theme was increased homozygosity, indicating that inbreeding rather than outbreeding depression gives rise to some of the deleterious phenotypes segregating in wild A. arenosa populations

A Truncated Singleton NLR Causes Hybrid Necrosis in Arabidopsis thaliana

Hybrid necrosis in plants arises from conflict between divergent alleles of immunity genes contributed by different parents, resulting in autoimmunity. We investigate a severe hybrid necrosis case in Arabidopsis thaliana, where the hybrid does not develop past the cotyledon stage and dies 3 weeks after sowing. Massive transcriptional changes take place in the hybrid, including the upregulation of most NLR (nucleotide-binding site leucine-rich repeat) disease-resistance genes. This is due to an incompatible interaction between the singleton TIR-NLR gene DANGEROUS MIX 10 (DM10), which was recently relocated from a larger NLR cluster, and an unlinked locus, DANGEROUS MIX 11 (DM11). There are multiple DM10 allelic variants in the global A. thaliana population, several of which have premature stop codons. One of these, which has a truncated LRR-PL (leucine-rich repeat [LRR]-post-LRR) region, corresponds to the DM10 risk allele. The DM10 locus and the adjacent genomic region in the risk allele carriers are highly differentiated from those in the nonrisk carriers in the global A. thaliana population, suggesting that this allele became geographically widespread only relatively recently. The DM11 risk allele is much rarer and found only in two accessions from southwestern Spain-a region from which the DM10 risk haplotype is absent-indicating that the ranges of DM10 and DM11 risk alleles may be nonoverlapping