HIV-1 Protease and Reverse Transcriptase Control the Architecture of Their Nucleocapsid Partner

The HIV-1 nucleocapsid is formed during protease (PR)-directed viral maturation, and is transformed into pre-integration complexes following reverse transcription in the cytoplasm of the infected cell. Here, we report a detailed transmission electron microscopy analysis of the impact of HIV-1 PR and reverse transcriptase (RT) on nucleocapsid plasticity, using in vitro reconstitutions. After binding to nucleic acids, NCp15, a proteolytic intermediate of nucleocapsid protein (NC), was processed at its C-terminus by PR, yielding premature NC (NCp9) followed by mature NC (NCp7), through the consecutive removal of p6 and p1. This allowed NC co-aggregation with its single-stranded nucleic-acid substrate. Examination of these co-aggregates for the ability of RT to catalyse reverse transcription showed an effective synthesis of double-stranded DNA that, remarkably, escaped from the aggregates more efficiently with NCp7 than with NCp9. These data offer a compelling explanation for results from previous virological studies that focused on i) Gag processing leading to nucleocapsid condensation, and ii) the disappearance of NCp7 from the HIV-1 pre-integration complexes. We propose that HIV-1 PR and RT, by controlling the nucleocapsid architecture during the steps of condensation and dismantling, engage in a successive nucleoprotein-remodelling process that spatiotemporally coordinates the pre-integration steps of HIV-1. Finally we suggest that nucleoprotein remodelling mechanisms are common features developed by mobile genetic elements to ensure successful replication

Le Fibroscan®, un nouvel outil ambulatoire (étude de son impact dans la prise en charge des patients co-infectés VIH-VHC à Marseille)

AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Qualité de vie des patients co-infectés par le VIH-VHC après un traitement anti-VHC (quels bénéfices sur le long terme ? Le point de vue des médecins généralistes, médecins traitants de ces patients, au travers d'une enquête)

AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocSudocFranceF

Hepatitis B Virus Genomics Knocking at the Door of Routine Diagnostic Laboratories

International audienc

Do Malassezia yeasts colonize the guts of people living with HIV?

Malassezia yeasts are commensals of human skin. In contrast to culture-based studies, metagenomic studies have detected abundant Malassezia reads in the gut, especially in patients living with HIV. Whether Malassezia colonizes and persists in the gut remains an open question. This study aimed to describe the influence of HIV-associated immunodeficiency on gut colonization by Malassezia and to assess whether Malassezia are alive. Stool samples were prospectively collected over one-five visits from ten controls and 23 patients living with HIV (10 had CD4  500/mm3). Each sample was cultured and subjected to Malassezia viability PCR and both fungal and bacterial metabarcoding. Abundant M. furfur colonies were cultured from an HIV-immunocompromised patient. M. furfur and M. globosa were isolated in very low quantities from healthy volunteers. Viability Malassezia-specific qPCR was positive in three HIV-immunocompromised patients. Metagenomic analyses showed that Malassezia reads were significantly more abundant in immunocompromised patients living with HIV and erratic over time in all participants. Our findings emphasise that Malassezia are rarely cultured from human stool samples, despite the use of specific culture media. Although HIV-related immunosuppression appears to be associated with the presence of Malassezia, these yeasts do not persist and colonise the gut, even in immunocompromised patients

Malassezia yeast population dynamics on the skin of patients living with HIV

International audienceAbstract Malassezia species are lipid-dependent yeasts of the normal skin mycobiota in humans and some animals. Yet, both the dynamic of Malassezia skin colonization and the associated fungal and bacterial skin microbiome remain unknown in HIV+ patients. This study aimed to compare Malassezia yeast community structure and associated microbiome on the healthy skin of HIV+ patients and healthy controls. A total of 23 HIV+ patients and 10 healthy controls were included and followed-up for a maximum of 5 visits over 10–17 months. At each visit, chest, face, nasolabial fold, and scalp skin samples were subjected to both culture and MALDI-TOF MS identification, and ITS/16S metabarcoding. The participants were categorized according to their Malassezia colony forming unit (CFU) abundance. Malassezia were cultured from each participant at each visit. HIV+ patients were highly colonized on all visits with CFU > 100. Malassezia sympodialis and M. globosa were the most dominant species. Malassezia furfur and M. dermatis were more prevalent in HIV+ than in healthy participants. Malassezia sympodialis prevalence was stable at each sampling sites over time. Malassezia furfur prevalence was stable and more abundant over time on HIV+ patients’ chest. The metabarcoding analysis suggested a higher fungal and bacterial diversity and an increased abundance of Cladosporium halotolerans and Streptococcus in HIV+ patients than in controls. Overall, HIV+ patients display a high skin colonization by Malassezia yeasts and a dysbiosis of both fungal and bacterial communities

Detection of the newly characterized HIV CRF56_cpx in Marseille, southeastern France

SummaryObjectivesWe aimed to seek HIV sequences highly similar to CRF56-cpx, a recently described newly circulating B/CRF02/G recombinant HIV, in our local clinical microbiology laboratory sequence database.MethodsA recently implemented tool that combines a databank of all HIV nucleotide sequences obtained at our clinical microbiology laboratory with a search tool that uses BLAST was used. A comparative and phylogenetic analysis of HIV protease and reverse transcriptase fragments was performed.ResultsWe identified two sequences that were clustered with CRF56-cpx with a bootstrap value of 99% in phylogenetic analyses; these were obtained from two patients diagnosed with HIV in 2009–2011. HIV protease–reverse transcriptase sequences obtained from these two patients shared a mean identity of 98.2±0.2% with previously described CRF56-cpx sequences. Both case patients diagnosed with HIV in our centre were highly sexually active men who have sex with men.ConclusionsOur findings highlight the continuous expansion of HIV diversity in France and indicate that real-time surveillance of HIV molecular epidemiology, including the comparison of sequences from laboratory, national, and international databases, might be helpful to identify the emergence, circulation, and transmission of viral strains