Gut microbiome signatures linked to HIV-1 reservoir size and viremia control

The potential role of the gut microbiome as a predictor of immune-mediated HIV-1 control in the absence of antiretroviral therapy (ART) is still unknown. In the BCN02 clinical trial, which combined the MVA.HIVconsv immunogen with the latency-reversing agent romidepsin in early-ART treated HIV-1 infected individuals, 23% (3/13) of participants showed sustained low-levels of plasma viremia during 32 weeks of a monitored ART pause (MAP). Here, we present a multi-omics analysis to identify compositional and functional gut microbiome patterns associated with HIV-1 control in the BCN02 trial. Viremic controllers during the MAP (controllers) exhibited higher Bacteroidales/Clostridiales ratio and lower microbial gene richness before vaccination and throughout the study intervention when compared to non-controllers. Longitudinal assessment indicated that the gut microbiome of controllers was enriched in pro-inflammatory bacteria and depleted in butyrate-producing bacteria and methanogenic archaea. Functional profiling also showed that metabolic pathways related to fatty acid and lipid biosynthesis were significantly increased in controllers. Fecal metaproteome analyses confirmed that baseline functional differences were mainly driven by Clostridial es. Participants with high baseline Bacteroidales/Clostridiales ratio had increased pre-existing immune activation-related transcripts. The Bacteroidales/Clostridiales ratio as well as host immune-activation signatures inversely correlated with HIV-1 reservoir size. The present proof-of-concept study suggests the Bacteroidales/Clostridiales ratio as a novel gut microbiome signature associated with HIV-1 reservoir size and immune-mediated viral control after ART interruption. The online version contains supplementary material available at 10.1186/s40168-022-01247-6

Gut microbiome signatures linked to HIV-1 reservoir size and viremia control

Background: The potential role of the gut microbiome as a predictor of immune-mediated HIV-1 control in the absence of antiretroviral therapy (ART) is still unknown. In the BCN02 clinical trial, which combined the MVA.HIVconsv immunogen with the latency-reversing agent romidepsin in early-ART treated HIV-1 infected individuals, 23% (3/13) of participants showed sustained low-levels of plasma viremia during 32 weeks of a monitored ART pause (MAP). Here, we present a multi-omics analysis to identify compositional and functional gut microbiome patterns associated with HIV-1 control in the BCN02 trial. Results: Viremic controllers during the MAP (controllers) exhibited higher Bacteroidales/Clostridiales ratio and lower microbial gene richness before vaccination and throughout the study intervention when compared to non-controllers. Longitudinal assessment indicated that the gut microbiome of controllers was enriched in pro-inflammatory bacteria and depleted in butyrate-producing bacteria and methanogenic archaea. Functional profiling also showed that metabolic pathways related to fatty acid and lipid biosynthesis were significantly increased in controllers. Fecal metaproteome analyses confirmed that baseline functional differences were mainly driven by Clostridiales. Participants with high baseline Bacteroidales/Clostridiales ratio had increased pre-existing immune activation-related transcripts. The Bacteroidales/Clostridiales ratio as well as host immune-activation signatures inversely correlated with HIV-1 reservoir size. Conclusions: The present proof-of-concept study suggests the Bacteroidales/Clostridiales ratio as a novel gut microbiome signature associated with HIV-1 reservoir size and immune-mediated viral control after ART interruption. Video abstract

Whole Genome Deep Sequencing of HIV-1 Reveals the Impact of Early Minor Variants Upon Immune Recognition During Acute Infection

Deep sequencing technologies have the potential to transform the study of highly variable viral pathogens by providing a rapid and cost-effective approach to sensitively characterize rapidly evolving viral quasispecies. Here, we report on a high-throughput whole HIV-1 genome deep sequencing platform that combines 454 pyrosequencing with novel assembly and variant detection algorithms. In one subject we combined these genetic data with detailed immunological analyses to comprehensively evaluate viral evolution and immune escape during the acute phase of HIV-1 infection. The majority of early, low frequency mutations represented viral adaptation to host CD8+ T cell responses, evidence of strong immune selection pressure occurring during the early decline from peak viremia. CD8+ T cell responses capable of recognizing these low frequency escape variants coincided with the selection and evolution of more effective secondary HLA-anchor escape mutations. Frequent, and in some cases rapid, reversion of transmitted mutations was also observed across the viral genome. When located within restricted CD8 epitopes these low frequency reverting mutations were sufficient to prime de novo responses to these epitopes, again illustrating the capacity of the immune response to recognize and respond to low frequency variants. More importantly, rapid viral escape from the most immunodominant CD8+ T cell responses coincided with plateauing of the initial viral load decline in this subject, suggestive of a potential link between maintenance of effective, dominant CD8 responses and the degree of early viremia reduction. We conclude that the early control of HIV-1 replication by immunodominant CD8+ T cell responses may be substantially influenced by rapid, low frequency viral adaptations not detected by conventional sequencing approaches, which warrants further investigation. These data support the critical need for vaccine-induced CD8+ T cell responses to target more highly constrained regions of the virus in order to ensure the maintenance of immunodominant CD8 responses and the sustained decline of early viremia

'And they knew that they were naked.' Nakedness in the Middle Ages

In Anlehnung an die berühmte Kontroverse zwischen Nobert Elias und Hans Peter Duerr um die Frage der Entstehung der Schamgrenzen im Verhältnis von Körper und Kultur wendet sich dieser Sammelband in inter- und transdisziplinärer Weise der 'Nacktheit im Mittelalter' zu. In 18 Beiträgen aus der gesamten Bandbreite geisteswissenschaftlicher Disziplinen (Geschichte, Islamwissenschaften, Kunstgeschichte, Latinistik, Literaturwissenschaften, Theologie und Philosophie) werden verschiedenste Aspekte entblößter Körper behandelt und umfassend, teilweise mit reichem Bildmaterial dargestellt.folg

genus & generatio. Rollenerwartungen und Rollenerfüllungen im Spannungsfeld der Geschlechter und Generationen in Antike und Mittelalter

Die Beiträge in diesem Band gehen zurück auf die dritte Nachwuchstagung des Bamberger DFG-Graduiertenkollegs „Generationenbewusstsein und Generationenkonflikte in Antike und Mittelalter“. Neben Aspekten der Generationenthematik stehen dabei vor allem Überlegungen zu den genderstudies und die Frage nach den Valenzen des Rollenbegriffs im Vordergrund, wodurch sich vielfältige interdisziplinäre Berührungs- und Schnittpunkte ergeben. Der Band umfasst Beiträge der Fächer Klassische Philologie, Geschichtswissenschaft, Romanistik und Germanistik in einem Untersuchungszeitraum von der Antike bis ins ausgehende Mittelalter

Finns det plats för både kvinnor och män? : Seminariemiljön vid Historiska institutionens grundutbildning ur ett genusperspektiv

Under vårterminen 2009 genomfördes en genusanalytisk undersökning av Historiska institutionens seminariemiljö. Syftet med undersökningen var att öka kunskapen om institutionens seminariemiljö ur ett genusperspektiv liksom medvetenheten om jämställdhet hos studenter och personal vid Historiska institutionen. Undersökningen var uppdelad i tre delar. Den första delen bestod av öppna observationer på A-, B- och C-kursen då bland annat kvinnors och mäns talutrymme kartlades. Den andra delen innefattade en enkät där studenternas syn på seminariemiljön och jämställdheten på institutionen undersöktes. Den tredje delen bestod av en gruppintervju med lärarna som fokuserade på seminarieledarnas roll och syn på seminariemiljön. Undersökningen visar att talutrymmet vid seminarierna är mer jämnt fördelat än vad som var förväntat med tanke på resultat från tidigare forskning. Det finns dock skillnader i hur kvinnor och män agerar och uttrycker sig i seminariesituationen, precis som det finns skillnader i seminarieformerna och undervisningssätten. De flesta studenter är nöjda med seminarieformen som sådan men en del kritik lyftes fram i enkäten då det gäller genusintegreringen på grundutbildningen. Ett annat resultat av undersökningen är att studenter och lärare har formulerat förslag till åtgärder för att förbättra jämställdheten och kvaliteten på undervisningen. Dessa åtgärdsförslag är av sådan karaktär att de även kan tillämpas på andra institutioner vid universitetet