Le paludisme dans les suites des interventions chirurgicales en région endémique

La fréquence de l'accès palustre dans les suites des interventions chirurgicales a été observée pendant trois mois, en 1992, dans le service de chirurgie de l'hôpital de Bobo-Dioulasso (Burkina Faso) où 6% des cent vingt opérés ont présenté un accès palustre, tous dus à #Plasmodium falciparum, pendant les cinq jours suivant l'intervention. Ce groupe ne présentait pas de caractéristique médicale ou sociale par rapport aux autres opérés. La fréquence de l'accès palustre dans les suites des interventions semble être souvent surestimée. Une recherche systématique de #Plasmodium en cas de fièvre est souhaitable. (Résumé d'auteur

HIV-1 competition experiments in humanized mice show that APOBEC3H imposes selective pressure and promotes virus adaptation

APOBEC3 (A3) family proteins are DNA cytosine deaminases recognized for contributing to HIV-1 restriction and mutation. Prior studies have demonstrated that A3D, A3F, and A3G enzymes elicit a robust anti-HIV-1 effect in cell cultures and in humanized mouse models. Human A3H is polymorphic and can be categorized into three phenotypes: stable, intermediate, and unstable. However, the anti-viral effect of endogenous A3H in vivo has yet to be examined. Here we utilize a hematopoietic stem cell-transplanted humanized mouse model and demonstrate that stable A3H robustly affects HIV-1 fitness in vivo. In contrast, the selection pressure mediated by intermediate A3H is relaxed. Intriguingly, viral genomic RNA sequencing reveled that HIV-1 frequently adapts to better counteract stable A3H during replication in humanized mice. Molecular phylogenetic analyses and mathematical modeling suggest that stable A3H may be a critical factor in human-to-human viral transmission. Taken together, this study provides evidence that stable variants of A3H impose selective pressure on HIV-1

APOBEC3G and APOBEC3F rarely co-mutate the same HIV genome

Abstract Background The human immune proteins APOBEC3G and APOBEC3F (hA3G and hA3F) induce destructive G-to-A changes in the HIV genome, referred to as ‘hypermutation’. These two proteins co-express in human cells, co-localize to mRNA processing bodies and might co-package into HIV virions. Therefore they are expected to also co-mutate the HIV genome. Here we investigate the mutational footprints of hA3G and hA3F in a large population of full genome HIV-1 sequences from naturally infected patients to uniquely identify sequences hypermutated by either or both of these proteins. We develop a method of identification based on the representation of hA3G and hA3F target and product motifs that does not require an alignment to a parental/consensus sequence. Results Out of nearly 100 hypermutated HIV-1 sequences only one sequence from the HIV-1 outlier group showed clear signatures of co-mutation by both proteins. The remaining sequences were affected by either hA3G or hA3F. Conclusion Using a novel method of identification of HIV sequences hypermutated by the hA3G and hA3F enzymes, we report a very low rate of co-mutation of full-length HIV sequences, and discuss the potential mechanisms underlying this.</p

Insights into the motif preference of APOBEC3 enzymes.

We used a multivariate data analysis approach to identify motifs associated with HIV hypermutation by different APOBEC3 enzymes. The analysis showed that APOBEC3G targets G mainly within GG, TG, TGG, GGG, TGGG and also GGGT. The G nucleotides flanked by a C at the 3' end (in +1 and +2 positions) were indicated as disfavoured targets by APOBEC3G. The G nucleotides within GGGG were found to be targeted at a frequency much less than what is expected. We found that the infrequent G-to-A mutation within GGGG is not limited to the inaccessibility, to APOBEC3, of poly Gs in the central and 3'polypurine tracts (PPTs) which remain double stranded during the HIV reverse transcription. GGGG motifs outside the PPTs were also disfavoured. The motifs GGAG and GAGG were also found to be disfavoured targets for APOBEC3. The motif-dependent mutation of G within the HIV genome by members of the APOBEC3 family other than APOBEC3G was limited to GA→AA changes. The results did not show evidence of other types of context dependent G-to-A changes in the HIV genome

A schematic of principal component analysis applied to the motif representation data of HIV sequences.

<p>A schematic of principal component analysis applied to the motif representation data of HIV sequences.</p

Percentage change of motifs within which G-to-A change(s) in the context of GG has occurred.

<p>The number of available GGs (i.e. mutability) has been used to normalize the results. a) Analysis of whole HIV genome; b) Analysis of the HIV genome without polypurine tracts. Hypermutated sequences (see reference <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0087679#pone.0087679-Armitage1" target="_blank">[5]</a> for details) are shown on the horizontal axes.</p

Principal component analysis of the motif representation data of HIV-1 sequences from subtypes/recombinant B, C, A1 and 01_AE.

<p>a) Scores plot (PC11 vs. PC13). Each point is an HIV-1 full genome sequence. The accession numbers of the two sequences that extend in the direction of mutation by APOBEC3F and/or other similar APOBEC3 members are shown near their points. b) Loadings plot (PC11 vs. PC13). Each point is a motif. The arrow shows the direction of GA→AA mutation by APOBEC3F and/or other similar APOBEC3 enzymes.</p

Conserved polypurine tracts shown in a representative alignment of 54 hypermutated HIV-1 sequences used in this study.

<p>Each line is a full genome hypermutated sequence within which the positions of GGGG motifs are shown by small triangles.</p