env Sequences of Simian Immunodeficiency Viruses from Chimpanzees in Cameroon Are Strongly Related to Those of Human Immunodeficiency Virus Group N from the Same Geographic Area

Human immunodeficiency virus type 1 (HIV-1) group N from Cameroon is phylogenetically close, in env, to the simian immunodeficiency virus (SIV) cpz-gab from Gabon and SIVcpz-US of unknown geographic origin. We screened 29 wild-born Cameroonian chimpanzees and found that three (Cam3, Cam4, and Cam5) were positive for HIV-1 by Western blotting. Mitochondrial DNA sequence analysis demonstrated that Cam3 and Cam5 belonged to Pan troglodytes troglodytes and that Cam4 belonged to P. t. vellerosus. Genetic analyses of the viruses together with serological data demonstrated that at least one of the two P. t. troglodytes chimpanzees (Cam5) was infected in the wild, and revealed a horizontal transmission between Cam3 and Cam4. These data confirm that P. t. troglodytes is a natural host for HIV-1-related viruses. Furthermore, they show that SIVcpz can be transmitted in captivity, from one chimpanzee subspecies to another. All three SIVcpz-cam viruses clustered with HIV-1 N in env. The full Cam3 SIVcpz genome sequence showed a very close phylogenetic relationship with SIVcpz-US, a virus identified in a P. t. troglodytes chimpanzee captured nearly 40 years earlier. Like SIVcpz-US, SIVcpz-cam3 was closely related to HIV-1 N in env, but not in pol, supporting the hypothesis that HIV-1 N results from a recombination event. SIVcpz from chimpanzees born in the wild in Cameroon are thus strongly related in env to HIV-1 N from Cameroon, demonstrating the geographic coincidence of these human and simian viruses and providing a further strong argument in favor of the origin of HIV-1 being in chimpanzees

Diversity of Pneumocystis jirovecii during infection revealed by ultra-deep pyrosequencing

Pneumocystis jirovecii is an uncultivable fungal pathogen responsible for Pneumocystis pneumonia (PcP) in immunocompromised patients, the physiopathology of which is only partially understood. The diversity of the Pneumocystis strains associated with acute infection has mainly been studied by Sanger sequencing techniques precluding any identification of rare genetic events (<20% frequency). We used next-generation sequencing to detect minority variants causing infection, and analyzed the complexity of the genomes of infection-causing P. jirovecii. Ultra-deep pyrosequencing (UDPS) of PCR amplicons of two nuclear target region (internal transcribed spacer 2 (ITS2) and dihydrofolate reductase (DHFR)) and one mitochondrial DNA target region (the mitochondrial ribosomal RNA large subunit gene (mtLSU)) was performed on 31 samples from 25 patients. UDPS revealed that almost all patients (n=23/25, 92%) were infected with mixtures of strains. An analysis of repeated samples from six patients showed that the proportion of each variant change significantly (by up to 30%) over time on treatment in three of these patients. A comparison of mitochondrial and nuclear UDPS data revealed heteroplasmy in Pneumocystis jirovecii. The recognition site for the homing endonuclease I-SceI was recovered from the mtLSU gene, whereas its two conserved motifs of the enzyme were not. This suggests that heteroplasmy may result from recombination induced by unidentified homing endonucleases.This study sheds new light on the biology of P. jirovecii during infection. PcP results from infection not with a single microorganism, but with a complex mixture of different genotypes, the proportions of which change over time due intricate selection and reinfection mechanisms that may differ between patients, treatments and predisposing diseases

Higher convergence of human-great ape enteric eukaryotic viromes in central African forest than in a European zoo: a One Health analysis

Abstract Human-animal pathogenic transmissions threaten both human and animal health, and the processes catalyzing zoonotic spillover and spillback are complex. Prior field studies offer partial insight into these processes but overlook animal ecologies and human perceptions and practices facilitating human-animal contact. Conducted in Cameroon and a European zoo, this integrative study elucidates these processes, incorporating metagenomic, historical, anthropological and great ape ecological analyses, and real-time evaluation of human-great ape contact types and frequencies. We find more enteric eukaryotic virome sharing between Cameroonian humans and great apes than in the zoo, virome convergence between Cameroonian humans and gorillas, and adenovirus and enterovirus taxa as most frequently shared between Cameroonian humans and great apes. Together with physical contact from hunting, meat handling and fecal exposure, overlapping human cultivation and gorilla pillaging in forest gardens help explain these findings. Our multidisciplinary study identifies environmental co-use as a complementary mechanism for viral sharing

Multidrug-resistant Neisseria gonorrhoeae failing treatment with ceftriaxone and doxycycline in France, November 2017

We report a multidrug-resistant Neisseria gonorrhoeae urogenital and pharyngeal infection with ceftriaxone resistance and intermediate resistance to azithromycin in a heterosexual woman in her 20s in France. Treatment with ceftriaxone plus doxycycline failed for the pharyngeal localisation. Whole-genome sequencing of isolate F90 identified MLST1903, NG-MAST ST3435, NG-STAR233, and relevant resistance determinants. F90 showed phenotypic and genotypic similarities to an internationally spreading multidrug-resistant and ceftriaxone-resistant clone detected in Japan and subsequently in Australia, Canada and Denmark

Affinity-Purified Respiratory Syncytial Virus Antibodies from Intravenous Immunoglobulin Exert Potent Antibody-Dependent Cellular Cytotoxicity

Mixed infections are one of the major therapeutic challenges, as the current strategies have had limited success. One of the most common and widespread conditions of mixed infection is respiratory syncytial virus-mediated pathology of the respiratory tract in children. There is a dire need for the development of novel therapeutic approaches during mixed infections. Therapeutic intravenous immunoglobulin preparations, obtained from plasma pools of healthy donors have been used in immune deficiencies. This study was thus designed to characterize the functional efficacy of RSV-specific antibodies in IVIg. To explore the functional ability of these affinity-purified RSV-specific antibodies, the antibody-dependent and complement dependent cytotoxicity was determined using peripheral cells of healthy donors. This study demonstrates the existence of highly potent RSV-specific antibodies in IVIg preparations and provides the basis for the use of IVIg as broad-spectrum protective shield to RSV-infected children during mixed infections

Reactivity of native IVIg and purified anti-RSV G antibodies.

<p><b>A)</b> Reactivity of various IVIg preparations (labeled P1 to P9) with the recombinant G protein of RSV. <b>B)</b> Reactivity of IVIg (line with circle) and affinity-purified anti-RSV IgG (line with square) with the recombinant G protein of RSV.</p

Antibody-dependent cell-mediated cytotoxicity (ADCC) activity.

<p>The RSV infected Hep-2 cells were used as target cells and PBMCs were used as effector cells. The cells were incubated with various concentrations of IVIg (line with circle), anti-RSV G IgG (line with square) and anti-RSV F IgG (line with blank circle). The assay was performed at the ratio of 50∶1 (Effector: Target) in triplicates. Data were analyzed by two-way ANOVA followed by Bonferroni test for comparison between IVIg, anti-RSV G IgG and anti-RSV F IgG treated cells. Results are mean ± standard error of the mean of values obtained with PBMCs (effector cells) from 6 individual donors in three independent experiments. ***<i>P</i><0.001, and *<i>P</i><0.05.</p

Complement-dependent cytotoxicity (CDC) activity.

<p>The RSV infected Hep-2 cells were used, as target cells and rabbit complement serum was the source of complement. The cells were incubated with various concentrations of IVIg (line with circle), anti-RSV G IgG (line with square) and anti-RSV F IgG (line with blank circle), in triplicates. Data were analyzed by two-way ANOVA followed by Bonferroni test for comparison between IVIg, anti-RSV G IgG and anti-RSV F IgG treated cells. Results are mean ± standard error of values obtained in three independent experiments. ns: non-significant.</p