Mosquito Feeding Habits in Coastal French Guiana: Mammals in the Crosshairs?

Pathogens transmitted by mosquitoes (Diptera, Culicidae) in sylvatic or urban cycles involve wild or domestic animals and humans, driven by various mosquito species with distinct host preferences. Understanding mosquito-host associations is crucial for ecological insights and pathogen surveillance. In this study, we analyzed mosquito blood meals from coastal French Guiana by amplifying and sequencing host DNA from blood-fed females.

Paramyxovirus circulation in bat species from French Guiana.

Bats are recognized as reservoirs of numerous viruses. Among them, paramyxoviruses, for example, Hendra and Nipah viruses, are highly pathogenic to humans. Nothing is known regarding the circulation of this viral family in bats from French Guiana.

Using phylogenetic surveillance and epidemiological data to understand the HIV-1 transmission dynamics in French Guiana.

Objective: The aim of this study was to understand the transmission dynamics of the HIV-1 subtype B epidemic in French Guiana and the factors that shaped the expansion of major phylogenetic transmission clusters.

Design: HIV-1 subtype B pol sequences with associated epidemiological data obtained from 703 treatment-naive patients living in French Guiana between 2006 and 2012, which correspond to 91% of all HIV cases diagnosed in that period, were employed in this study.

Methods: Maximum likelihood and Bayesian methods were used to construct phylogenetic trees, identify transmission clusters and estimate intervals between successive infections.

The HIV-1 Subtype B Epidemic in French Guiana and Suriname Is Driven by Ongoing Transmissions of Pandemic and Non-pandemic Lineages.

The HIV-1 subtype B epidemic in French Guiana and Suriname is characterized by the co-circulation of the globally disseminated "B" lineage and of non-pandemic subtype B lineages of Caribbean origin (B). To reconstruct the spatiotemporal pattern of spread of those viral lineages circulating in these two countries, a total of 361 HIV-1 subtype B sequences recovered from treatment-naive adult patients from French Guiana and Suriname between 2006 and 2012 were combined with B and B reference sequences. Major Guianese/Surinamese B and B lineages were identified by Maximum Likelihood phylogenetic analysis and the spatiotemporal and demographic parameters estimated using a Bayesian coalescent-based method.

Development of molecular and cellular tools to decipher the type I IFN pathway of the common vampire bat.

Though the common vampire bat, Desmodus rotundus, is known as the main rabies virus reservoir in Latin America, no tools are available to investigate its antiviral innate immune system. To characterize the IFN-I pathway, we established an immortalized cell line from a D. rotundus fetal lung named FLuDero.

Virome analysis of two sympatric bat species (Desmodus rotundus and Molossus molossus) in French Guiana.

Environmental disturbances in the Neotropics (e.g., deforestation, agriculture intensification, urbanization) contribute to an increasing risk of cross-species transmission of microorganisms and to disease outbreaks due to changing ecosystems of reservoir hosts.

Absence of vaccinia virus detection in a remote region of the Northern Amazon forests, 2005-2015.

Vaccinia virus (VACV) circulates in Brazil and other South America countries and is responsible for a zoonotic disease that usually affects dairy cattle and humans, causing economic losses and impacting animal and human health. Furthermore, it has been detected in wild areas in the Brazilian Amazon. To better understand the natural history of VACV, we investigated its circulation in wildlife from French Guiana, a remote region in the Northern Amazon forest.

HIV-1 Genetic Diversity and Drug Resistance Mutations Among Treatment-Naive Adult Patients in Suriname.

The molecular epidemiologic profile of HIV-1 in Suriname was determined through protease (PR) and reverse transcriptase (RT) sequences obtained from HIV-1 strains collected from 100 drug-naive HIV-1-infected persons. Subtype determination revealed that most viruses were of subtype B (94.9%) in both PR and RT genomic regions, followed by B/D recombinants (5.

Complete Genome Sequence of a Vampire Bat Rabies Virus from French Guiana.

A rabies virus was detected in a common vampire bat (Desmodus rotundus) in French Guiana. Its genomic sequence was obtained and found to be closely related to other hematophagous bat-related viruses that widely circulate in the northern Amazon region. This virus is named AT6.

HIV-1 Pol Gene Polymorphism and Antiretroviral Resistance Mutations in Treatment-Naive Adult Patients in French Guiana Between 2006 and 2012.

Little information is available on the molecular epidemiologic profile of HIV-1 in French Guiana, the French department with the highest HIV/AIDS incidence. To follow the evolution of HIV-1 diversity, we carried out a molecular analysis of HIV-1 isolates from 305 treatment-naive patients between 2006 and 2012. Protease and reverse-transcriptase sequences were obtained for subtype characterization, polymorphism analysis, and identification of drug resistance mutations.

Bioecological Drivers of Rabies Virus Circulation in a Neotropical Bat Community.

Introduction: In addition to the commonly accepted importance of the vampire bat in the maintenance and transmission of the rabies virus (RABV) in South America, RABV infection of other species is widely evidenced, challenging their role in the viral cycle.

Methodology / Principles Findings: To identify the bioecological drivers of RABV circulation in neotropical bat communities, we conducted a molecular and serological survey on almost 1,000 bats from 30 species, and a 4-year longitudinal survey in two colonies of vampire bats in French Guiana. RABV was molecularly detected in a common vampire and in a frugivorous bat.

Intralesional regulatory T-cell suppressive function during human acute and chronic cutaneous leishmaniasis due to Leishmania guyanensis.

The levels of regulatory T cells (Treg cells), analyzed by Foxp3 mRNA expression, were determined in lesions from patients with acute cutaneous leishmaniasis (ACL) and chronic cutaneous leishmaniasis (CCL). We demonstrated that Treg cells preferentially accumulate in lesions from ACL patients during the early phase of infection (lesion duration of less than 1 month). In addition, levels of Foxp3 mRNA transcripts were significantly higher in specimens from patients with CCL than in those from patients with ACL, suggesting a critical role of intralesional Treg cells in CCL.

A novel cellular RNA helicase, RH116, differentially regulates cell growth, programmed cell death and human immunodeficiency virus type 1 replication.

In an effort to define novel cellular factors regulating human immunodeficiency virus type 1 (HIV-1) replication, a differential display analysis has been performed on endogenously infected cells stimulated with the HIV-suppressive immunomodulator Murabutide. In this study, the cloning and identification of a Murabutide-downregulated gene, named RH116, bearing classical motifs that are characteristic of the DExH family of RNA helicases, are reported. The 116 kDa encoded protein shares 99.

A phase I study of a six-week cycle of immunotherapy with Murabutide in HIV-1 patients naive to antiretrovirals.

Background: Limitations in the use of antiretroviral therapy suggest the need for additional approaches to enhance immune restoration and the control of HIV-1 replication. Therefore, we evaluated the clinical tolerance and biological effects of immunotherapy with the synthetic immunomodulator Murabutide in 9 treatment-naive HIV-1 patients presenting with CD4+ lymphocyte counts >500 cells/mm3 and plasma viral loads <30.000 copies/ml.

Clinical and immunological effects of a 6 week immunotherapy cycle with murabutide in HIV-1 patients with unsuccessful long-term antiretroviral treatment.

In an effort to evaluate the potential of non-specific immunotherapy in restoring global immunity, we have examined the clinical tolerance and biological effects of a 6 week administration of the immunomodulator, murabutide, in chronically infected HIV-1 patients. Forty-two subjects, presenting weak immune reconstitution and ineffective virus suppression following long-term highly active antiretroviral therapy (HAART), were randomized to receive, or not, murabutide 7 mg/day on five consecutive days/week. Clinical and immunological parameters were monitored before and after the immunotherapy period.

Discordant effects of interleukin-2 on viral and immune parameters in human immunodeficiency virus-1-infected monocyte-derived mature dendritic cells.

Use of interleukin-2 (IL-2) in the immunotherapy of human immunodeficiency virus (HIV) has frequently resulted in the restoration of CD4 lymphocyte counts but not of virus-specific responses. We reasoned that the absence of reconstituted functional immune parameters could be related to the inability of IL-2 to correct HIV-induced dysfunctions in antigen-presenting cells. In this study, we used in vitro-differentiated monocyte-derived macrophages (MDMs) and mature dendritic cells (MDDCs), acutely infected with primary HIV-1 isolates, to analyse the effects of IL-2 on virus replication, co-receptor expression, and cytokine or chemokine release.

Clinical tolerance and immunologic effects after single or repeated administrations of the synthetic immunomodulator murabutide in HIV-1-infected patients.

Correction of the virus-induced deficits in innate immunity of HIV-infected subjects could well contribute to enhanced immune recovery and efficacious control of viral replication. The safe synthetic immunomodulator Murabutide (ISTAC Biotechnology, Lille, France) has been found to regulate the function of antigen-presenting cells and to selectively activate CD4 lymphocytes leading to dramatic suppression of HIV replication, in vitro. Therefore, as a first step toward the evaluation of the immunotherapeutic potential of Murabutide in HIV disease, we have conducted two phase 1/2 clinical trials to address the safety and the immunologic effects of Murabutide administration into HIV-infected subjects receiving antiretroviral therapy.

The transcriptional response of human macrophages to murabutide reflects a spectrum of biological effects for the synthetic immunomodulator.

The synthetic immunomodulator murabutide (MB) presents multiple biological activities with minimal toxicity in animals and in man. Although MB is known to target cells of the reticuloendothelial system and to regulate cytokine synthesis, the molecular mechanisms underlying several of its biological effects are still largely unknown. In an effort to define cellular factors implicated in the immunomodulatory and HIV-suppressive activities of MB, we have undertaken profiling the regulated expression of genes in human monocyte-derived macrophages (MDM) following a 6-h stimulation with this synthetic glycopeptide.

Variations in serum IL-7 and 90K/Mac-2 binding protein (Mac-2 BP) levels analysed in cohorts of HIV-1 patients and correlated with clinical changes following antiretroviral therapy.

Serum levels of interleukin-7 (IL-7), a non-redundant cytokine that plays a crucial role in lymphopoiesis, are known to be elevated in HIV-1-infected subjects. To examine further the association between levels of IL-7, CD4+ cell counts and viraemia, we analysed these parameters in a large cohort of HIV-1 patients along with serum levels of 90K, a marker of disease severity but with no established involvement in lymphopoiesis. While IL-7 levels were only found to correlate with CD4+ cell counts, 90K levels presented strong correlations with both CD4+ cell numbers and with plasma viral loads (VLs).

Clinical tolerance and profile of cytokine induction in healthy volunteers following the simultaneous administration of ifn-alpha and the synthetic immunomodulator murabutide.

As the therapeutic use of interferon-alpha (IFN-alpha) is limited by a dose-dependent toxicity and variable efficacy, ways of improving the therapeutic index of the cytokine are being sought. Murabutide (N-acetyl muramyl-L-alanyl-D-glutamine-O-n-butyl-ester) (ISTAC Biotechnology, Lille, France) is a safe synthetic and clinically acceptable immunomodulator that enhances the biologic activities of IFN-alpha in different experimental models. We evaluated in healthy human volunteers tolerance of the coadministration of Murabutide with increasing doses of IFN-alpha.

Macrophage stimulation with Murabutide, an HIV-suppressive muramyl peptide derivative, selectively activates extracellular signal-regulated kinases 1 and 2, C/EBPbeta and STAT1: role of CD14 and Toll-like receptors 2 and 4.

The smallest unit of bacterial peptidoglycans known to be endowed with biological activities is muramyl dipeptide (MDP). A clinically acceptable synthetic derivative of MDP, namely murabutide (MB), has been found to present interesting pharmacological properties and to suppress HIV-1 replication in monocyte-derived macrophages (MDM). We have addressed the signaling events activated in MDM following stimulation with either MB or the potent immunostimulant LPS.

Selective regulation of human immunodeficiency virus-infected CD4(+) lymphocytes by a synthetic immunomodulator leads to potent virus suppression in vitro and in hu-PBL-SCID mice.

We have previously observed that the synthetic immunomodulator Murabutide inhibits human immunodeficiency virus type 1 (HIV-1) replication at multiple levels in macrophages and dendritic cells. The present study was designed to profile the activity of Murabutide on CD8-depleted phytohemagglutinin-activated lymphocytes from HIV-1-infected subjects and on the outcome of HIV-1 infection in severe combined immunodeficiency mice reconstituted with human peripheral blood leukocytes (hu-PBL-SCID mice). Maintaining cultures of CD8-depleted blasts from 36 patients in the presence of Murabutide produced dramatically reduced levels of viral p24 protein in the supernatants.

The synthetic immunomodulator murabutide controls human immunodeficiency virus type 1 replication at multiple levels in macrophages and dendritic cells.

Macrophages and dendritic cells are known to play an important role in the establishment and persistence of human immunodeficiency virus (HIV) infection. Besides antiretroviral therapy, several immune-based interventions are being evaluated with the aim of achieving better control of virus replication in reservoir cells. Murabutide is a safe synthetic immunomodulator presenting a capacity to enhance nonspecific resistance against viral infections and to target cells of the reticuloendothelial system.

Human chemokine receptors CCR5, CCR3 and CCR2B share common polarity motif in the first extracellular loop with other human G-protein coupled receptors implications for HIV-1 coreceptor function.

Chemokine receptors (CRs) are 7-helix membrane proteins from the family of G-protein coupled receptors (GPCRs). A few human CRs act as cofactors for macrophage-tropic (M-tropic) human immunodeficiency virus type-1 (HIV-1) entry into cells, while others do not. In this study, we describe an application of molecular modeling techniques to delineate common molecular determinants that might be related to coreceptor activity, and the use of the data to identify other GPCRs as putative cofactors for M-tropic HIV-1 entry.