Genetic diversity and dynamics of the Noir Marron settlement in French Guyana : A study combining mitochondrial DNA, Y chromosome and HTLV-1 genotyping [Abstract]

The Noir Marron are the direct descendants of thousands of African slaves deported to the Guyanas during the Atlantic Slave Trade and later escaped mainly from Dutch colonial plantations. Six ethnic groups are officially recognized, four of which are located in French Guyana: the Aluku, the Ndjuka, the Saramaka, and the Paramaka. The aim of this study was: (1) to determine the Noir Marron settlement through genetic exchanges with other communities such as Amerindians and Europeans; (2) to retrace their origins in Africa. Buffy-coat DNA from 142 Noir Marron, currently living in French Guyana, were analyzed using mtDNA (typing of SNP coding regions and sequencing of HVSI/II) and Y chromosomes (typing STR and SNPs) to define their genetic profile. Results were compared to an African database composed by published data, updated with genotypes of 82 Fon from Benin, and 128 Ahizi and 63 Yacouba from the Ivory-Coast obtained in this study for the same markers. Furthermore, the determination of the genomic subtype of HTLV-1 strains (env gp21 and LTR regions), which can be used as a marker of migration of infected populations, was performed for samples from 23 HTLV-1 infected Noir Marron and compared with the corresponding database. MtDNA profiles showed a high haplotype diversity, in which 99% of samples belonged to the major haplogroup L, frequent in Africa. Each haplotype was largely represented on the West African coast, but notably higher homologies were obtained with the samples present in the Gulf of Guinea. Y Chromosome analysis revealed the same pattern, i.e. a conservation of the African contribution to the Noir Marron genetic profile, with 98% of haplotypes belonging to the major haplogroup E1b1a, frequent in West Africa. The genetic diversity was higher than those observed in African populations, proving the large Noir Marron’s fatherland, but a predominant identity in the Gulf of Guinea can be suggested. Concerning HTLV-1 genotyping, all the Noir Marron strains belonged to the large Cosmopolitan A subtype. However, among them 17/23 (74%) clustered with the West African clade comprizing samples originating from Ivory-Coast, Ghana, Burkina-Fasso and Senegal, while 3 others clustered in the Trans-Sahelian clade and the remaining 3 were similar to strains found in individuals in South America. Through the combined analyses of three approaches, we have provided a conclusive image of the genetic profile of the Noir Marron communities studied. The high degree of preservation of the African gene pool contradicts the expected gene flow that would correspond to the major cultural exchanges observed between Noir Marron, Europeans and Amerindians. Marital practices and historical events could explain these observations. Corresponding to historical and cultural data, the origin of the ethnic groups is widely dispatched throughout West Africa. However, all results converge to suggest an individualization from a major birthplace in the Gulf of Guinea

A standardized framework for accurate, high-throughput genotyping of recombinant and non-recombinant viral sequences

Human immunodeficiency virus type-1 (HIV-1), hepatitis B and C and other rapidly evolving viruses are characterized by extremely high levels of genetic diversity. To facilitate diagnosis and the development of prevention and treatment strategies that efficiently target the diversity of these viruses, and other pathogens such as human T-lymphotropic virus type-1 (HTLV-1), human herpes virus type-8 (HHV8) and human papillomavirus (HPV), we developed a rapid high-throughput-genotyping system. The method involves the alignment of a query sequence with a carefully selected set of pre-defined reference strains, followed by phylogenetic analysis of multiple overlapping segments of the alignment using a sliding window. Each segment of the query sequence is assigned the genotype and sub-genotype of the reference strain with the highest bootstrap (>70%) and bootscanning (>90%) scores. Results from all windows are combined and displayed graphically using color-coded genotypes. The new Virus-Genotyping Tools provide accurate classification of recombinant and non-recombinant viruses and are currently being assessed for their diagnostic utility. They have incorporated into several HIV drug resistance algorithms including the Stanford (http://hivdb.stanford.edu) and two European databases (http://www.umcutrecht.nl/subsite/spread-programme/ and http://www.hivrdb.org.uk/) and have been successfully used to genotype a large number of sequences in these and other databases. The tools are a PHP/JAVA web application and are freely accessible on a number of servers including

Frequent and Recent Human Acquisition of Simian Foamy Viruses Through Apes' Bites in Central Africa

Human infection by simian foamy viruses (SFV) can be acquired by persons occupationally exposed to non-human primates (NHP) or in natural settings. This study aimed at getting better knowledge on SFV transmission dynamics, risk factors for such a zoonotic infection and, searching for intra-familial dissemination and the level of peripheral blood (pro)viral loads in infected individuals. We studied 1,321 people from the general adult population (mean age 49 yrs, 640 women and 681 men) and 198 individuals, mostly men, all of whom had encountered a NHP with a resulting bite or scratch. All of these, either Pygmies (436) or Bantus (1085) live in villages in South Cameroon. A specific SFV Western blot was used and two nested PCRs (polymerase, and LTR) were done on all the positive/borderline samples by serology. In the general population, 2/1,321 (0.2%) persons were found to be infected. In the second group, 37/198 (18.6%) persons were SFV positive. They were mostly infected by apes (37/39) FV (mainly gorilla). Infection by monkey FV was less frequent (2/39). The viral origin of the amplified sequences matched with the history reported by the hunters, most of which (83%) are aged 20 to 40 years and acquired the infection during the last twenty years. The (pro)viral load in 33 individuals infected by a gorilla FV was quite low (<1 to 145 copies per 105 cells) in the peripheral blood leucocytes. Of the 30 wives and 12 children from families of FV infected persons, only one woman was seropositive in WB without subsequent viral DNA amplification. We demonstrate a high level of recent transmission of SFVs to humans in natural settings specifically following severe gorilla bites during hunting activities. The virus was found to persist over several years, with low SFV loads in infected persons. Secondary transmission remains an open question

An unusual presentation of Castleman's Disease:a case report

BACKGROUND: Castleman's disease (CD), a rare condition of uncertain etiology, involves a massive proliferation of lymphoid tissues and typically presents as mediastinal masses. We describe a patient with CD who presented with diffuse adenopathy involving the inguinal, paratracheal, retroperitoneal, axillary, and pelvic regions. CASE PRESENTATION: Case report describing presentation, work-up, management and clinical course of a patient with Castleman's disease in the setting of a county hospital in metropolitan area. Patient was treated with chemotherapeutic agents. CONCLUSIONS: To our knowledge, this represents the first case of CD involving an HIV-positive patient with a negative Human Herpes Virus (HHV-8) viral panel. Because patients with similar clinical histories are at high risk for the development of non-Hodgkin's lymphoma and Kaposi sarcoma, regular medical surveillance is recommended

AIDS-Kaposi Sarcoma and Classic Kaposi Sarcoma: are different ultrasound patterns related to different variants?

<p>Abstract</p> <p>Background</p> <p>Kaposi Sarcoma (KS) is a malignancy of endothelial skin cells with multifocal localization on the skin, lymph nodes and visceral organs. Although all clinical variants are associated with HHV-8 infection, specific differences in the clinical onset and in the natural history of AIDS-KS and Classic-KS have been described. The present randomised prospective-observational study aimed to investigate whether the ultrasound pattern and color Doppler flow imaging of vascularisation of skin lesions of patients with Classic KS (CKS) or AIDS-KS could provide useful information to the evaluation of clinical activity of the disease.</p> <p>Methods</p> <p>Cutaneous lesions of 24 patients with histologically confirmed KS were investigated using very high frequency ultrasound probes; 16 patients had CKS and 8 had AIDS-KS. HHV-8 infection was confirmed in all patients by investigating the specific humoral response to viral antigens. Immunological and virological parameters were also assessed to monitor HIV or HHV-8 viral infection. For each patient, a target skin lesion was selected on the basis of size (diameter from 0.4 to 2 cm). Each lesion was analyzed in terms of size, depth and color Doppler pattern.</p> <p>Results</p> <p>The B-mode ultrasound patterns of skin lesions did not differ when comparing CKS patients to AIDS-KS patients, whereas the color Doppler signal, which is associated with vascular activity, was detected in the KS lesions of 6/8 AIDS-KS patients (75.0%) and in 2/16 CKS (16,7%); the latter two patients showed a clinically progressive and extensive disease stage (IV B).</p> <p>Conclusions</p> <p>Our preliminary results suggest that small cutaneous KS lesions - in both CKS and AIDS-KS patients- display similar B-mode ultrasound patterns ( hypoechoic, well defined, superficial lesions). However, the color Doppler signal, which is associated with endothelial activity and angiogenesis, which play a substantial role in KS progression, could constitute a useful tool for evaluating disease activity.</p

NRP/Optineurin Cooperates with TAX1BP1 to Potentiate the Activation of NF-κB by Human T-Lymphotropic Virus Type 1 Tax Protein

Nuclear factor (NF)-κB is a major survival pathway engaged by the Human T-Lymphotropic Virus type 1 (HTLV-1) Tax protein. Tax1 activation of NF-κB occurs predominantly in the cytoplasm, where Tax1 binds NF-κB Essential Modulator (NEMO/IKKγ) and triggers the activation of IκB kinases. Several independent studies have shown that Tax1-mediated NF-κB activation is dependent on Tax1 ubiquitination. Here, we identify by co-immunoprecipitation assays NEMO-Related Protein (NRP/Optineurin) as a binding partner for Tax1 in HTLV-1 infected and Tax1/NRP co-expressing cells. Immunofluorescence studies reveal that Tax1, NRP and NEMO colocalize in Golgi-associated structures. The interaction between Tax1 and NRP requires the ubiquitin-binding activity of NRP and the ubiquitination sites of Tax1. In addition, we observe that NRP increases the ubiquitination of Tax1 along with Tax1-dependent NF-κB signaling. Surprisingly, we find that in addition to Tax1, NRP interacts cooperatively with the Tax1 binding protein TAX1BP1, and that NRP and TAX1BP1 cooperate to modulate Tax1 ubiquitination and NF-κB activation. Our data strongly suggest for the first time that NRP is a critical adaptor that regulates the assembly of TAX1BP1 and post-translationally modified forms of Tax1, leading to sustained NF-κB activation