13 research outputs found
Sex Hormone Modulation of HHV-8 Transcription
No full textHuman herpesvirus 8 (HHV-8) seroprevalence is similar in men and women, but Kaposi’s sarcoma (KS) is mostly seen in men, suggesting that sex hormones play a role in KS development. Previous work from our laboratory has identified potential estrogen response elements (EREs) within several regulatory genes’ promoters such as K8 (KB-Zip), ORF50 and ORF49. The HHV-8 EREs were found to bind the alpha estrogen receptor. The functionality of the K8 EREs was demonstrated using transient expression assays.
In this study, we tested the hypothesis that estrogen modulates the transcription of HHV-8 during latency or reactivation.
BCBL-1 cells are a B established from a pleural effusion lymphoma that is HHV-8 positive and Epstein-Barr virus (EBV) negative were used in the current study. Trex-BCBL-1 cells contain a doxycycline inducible ORF50 gene. MCF-7 cells are well studied breast cancer cell line. Production of infectious virus was determined using a TCID50 assay. Transcription of individual viral genes was measure by RT-PCR using specific primers. Measurement of cellular transcription following estrogen treatment was performed using estrogen signaling PCR arrays.
Treatment of BCBL-1 or TRex-BCBL-1 cells with estrogen did not result in viral reactivation as measure by flow cytometry. Estrogen treatment did not prevent TPA-induced reactivation of BCBL-1 cells or doxycycline-induced reactivation of TRex-BCBL-1 cells. treatment of BCBL-1 cells with estrogen alone resulted in a decrease of constitutive viral transcription. BCBL-1 express estrogen receptor beta (compared to MCF-7 cells which express estrogen receptor alpha).Treatment of MCF-7 cells with estrogen result in an increase in transcription of cellular genes while treatment of BCBL-1 resulted in a decrease in cellular transcription.
Our results suggest that estrogen can down-regulate both cellular and viral transcription in B cells. This down regulation may be involved in the lack of KS development in women.
Statement of Public Health relevance: Reactivation of HHV-8 has been shown to be associated with the advent of Kaposi’s sarcoma. By determining the role of estrogen in the transcription of viral genes and the estrogen receptors involved, potential therapeutic target can be found. The results from these experiments will help understand the biology of HHV-8, and pathology of Kaposi’s sarcoma
APOBEC3G Variants and Protection against HIV-1 Infection in Burkina Faso.
No full textStudies on host factors, particularly the APOBEC3G gene, have previously found an association with AIDS progression in some populations and against some HIV-1 strains but not others. Our study had two main objectives: firstly, to screen a population from Burkina Faso for three variants of APOBEC3G previously described, and secondly to analyze the effect of these three variants and their haplotypes on HIV-1 infection with Circulating Recombinant Forms (CRFs) present in Burkina Faso. This case control study involved 708 seropositive and seronegative individuals. Genotyping was done by the TaqMan allelic discrimination method. Minor allele frequencies of rs6001417 (p<0.05), rs8177832 (P<0.05), and rs35228531 (P<0.001) were higher in seronegative subjects. The rs6001417 and rs8177832 SNPs were associated with HIV-1 infection in an additive model (P<0.01). Furthermore the SNP rs35228531 was also associated with HIV-1 infection in a dominant model (P<0.001). Odds ratio analysis of genotypes and alleles of the different APOBEC3G variants showed that there is a strong association between the minor genetic variants, genotype of the three SNPs, and HIV-1 status. Haplotype analysis demonstrated that rs6001417, rs8177832, and rs35228531 are in linkage disequilibrium. The haplotype GGT from the rs6001417, rs8177832 and rs35228531 respectively has a protective effect OR = 0.54 [0.43-0.68] with P<0.001. There was also associations between the haplotypes GGC OR = 1.6 [1.1;-2.3] P<0.05, and CGC OR = 5.21 [2.4-11.3] P<0.001, which increase the risk of infection by HIV-1 from almost two (2) to five (5) fold. This study demonstrates an association of rs6001417, rs8177832, and rs35228531 of APOBEC3G with HIV-1 infection in a population from Burkina Faso
Major Polymorphisms of Genes Involved in Homocysteine Metabolism in Malaria Patients in Ouagadougou, Burkina Faso
No full textThis study analyzed the four main polymorphisms of the genes in homocysteine metabolism in malaria patients. Forty-two randomly selected subjects, diagnosed positive for Plasmodium falciparum, were included. The four genotypes were detected by real-time PCR using the MTHFR 677C>T, MTHFR 1298A>C, MTR 2756A>G, and MTRR 66A>G detection kit (Sacace Biotechnologies REF: T01002-96-S). The results revealed frequencies of 90% 677CC, 10% 677CT, and 00% 677TT for MTHFR C677T; 78.6% 1298AA, 19% 1298AC, and 2.4% 1298CC for MTHFR A1298C; 61.9% 2756AA, 33.3% 2756AG, and 4.8% 2756GG for MTR A2756G; and 50% of 66AA, 45% of 66AG, and 5% of 66GG for MTRR A66G. Correlations were found between A2756G MTR genotypes and parasitaemia (P=0.02), MTRR A66G and hemoglobin genotypes (P=0.009), and MTHFR A1298C and sex (P=0.01). This study demonstrated for the first time an association between the A2756G MTR alleles and Plasmodium falciparum malaria in Burkina Faso and gave an overview of the genotypic distribution of the major SNPs influencing the metabolism of homocysteine.</jats:p
Genetic diversity and occult hepatitis B infection in Africa: A comprehensive review.
No full textBACKGROUND: Occult hepatitis B infection (OBI) is a globally prevalent infection, with its frequency being influenced by the prevalence of hepatitis B virus (HBV) infection in a particular geographic region, including Africa. OBI can be transmitted through blood transfusions and organ transplants and has been linked to the development of hepatocellular carcinoma (HCC). The associated HBV genotype influences the infection. AIM: To highlight the genetic diversity and prevalence of OBI in Africa. METHODS: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and involved a comprehensive search on PubMed, Google Scholar, Science Direct, and African Journals Online for published studies on the prevalence and genetic diversity of OBI in Africa. RESULTS: The synthesis included 83 articles, revealing that the prevalence of OBI varied between countries and population groups, with the highest prevalence being 90.9% in patients with hepatitis C virus infection and 38% in blood donors, indicating an increased risk of HBV transmission through blood transfusions. Cases of OBI reactivation have been reported following chemotherapy. Genotype D is the predominant, followed by genotypes A and E. CONCLUSION: This review highlights the prevalence of OBI in Africa, which varies across countries and population groups. The study also demonstrates that genotype D is the most prevalent
APOBEC3G expression and HIV-1 infection in Burkina Faso
No full textAPOBEC3G is a potent inhibitor of HIV-1 replication, and act by deaminating cytidines in uracil on the negative strand of the viral cDNA. In this case-control study, APOBEC3G expression in subjects’ naïve to HAART infected by HIV-1 and the effect of APOBEC3G polymorphism on its expression were evaluated. The results show that the HIV-1 infected carriers of the G minor alleles of the variant rs8177832 had a higher expression of APOBEC3G mRNA than the controls carriers of the G minor allele. APOBEC3G polymorphisms could play an important role in the modulation of the HIV-1 dissemination
Prevalence of serological markers for Hepatitis B and C Viruses, human immuno-deficiency virus and Treponema pallidum among blood donors in Ouagadougou, Burkina Faso
No full textIn Sub-Saharan Africa, transfusion safety remains a challenge due to the high endemicity of blood-borne infections. This study aimed to determining the seroprevalence of human immunodeficiency virus (HIV), hepatitis B (HBV), hepatitis C (HCV), and Treponema pallidum among blood donors in Ouagadougou. This was a retrospective study in blood donor. HIV 1/2 and HCV antibodies and HBsAg were screened and confirmed with two ELISA (Enzyme Linked ImmunoSorbent Assay). While T. pallidum antibodies were also screened and confirmed with two serology tests. Only samples positive for both tests were counted as positive. Prevalence rates were calculated among first-time blood donors. Of 63,779 registered blood donors, 54,113 (84.84%) were first-time donors. Overall seroprevalences of HIV, HBV, HCV and Treponema pallidum were 2.56%, 11.87%, 5.89% and 3.22% respectively. Seroprevalences of HIV-HBV, HBV-HCV, HBV- T. pallidum and HIV-HBV-HCV co-infections were 0.36; 1.21; 0.54 and 0.02 respectively. The study reports that HIV, HBV, HCV and Treponema pallidum seroprevalences remain high among blood donors. These results highlight a potential infectious risk to blood products recipients
World Hepatitis Day in Burkina Faso, 2016: Awareness, Screening, Identification of HBV Markers, HBV/HCV Coinfection, and Vaccination
No full textDistribution of the cases and controls haplotypes.
No full text<p>Distribution of the cases and controls haplotypes.</p
Haploview APOBEC3G linkage disequilibrium plots for case and controls.
No full text<p>The figures are oriented 5’ to 3’, right to left, relative to the gene orientation on the minus strand. Fig 1a represents the LD plot of the case pairwise D’ between markers, and Fig 1b shows the LD plot of the control pairwise D’ between markers. Strong LD is indicated by red, while pink indicate uninformative values. LD blocks were created with the default algorithm in the Haploview software (version 4.1) that creates 95% confidence bounds. D’ was considered strong where 95% of the comparisons made are informative.</p
