Frauke Mücksch

This session takes a deep dive into microbiota, gut dysfunction and neuroinflammation and their connection to infection. The expression of HIV sensors in a range of tissues was presented and the session concluded with an excursion to SARS-CoV-2 susceptibility of motoneurons. Together, this session underlines the importance of tissue reservoirs.

J.Victor Garcia presented a study evaluating the effect of resident microbiota on HIV acquisition in the intestinal tract following oral or rectal exposure. For this, a germ-free humanized mouse model, the GF-BLT model, was established. Presence of resident microbiota increased HIV acquisition via both, oral and rectal exposure. Sarah Byrnes showed that inflammation in the gut of NHPs is associated with neuropathological changes in the brain, which is a reservoir of SIV that persists despite ART suppression. This was independent of SIV infection. These findings suggest that gut disruption may contribute to neurological outcomes in people living with HIV. Ashley George analyzed tissue samples from people with HIV using a CyTOF panel containing viral sensors and restriction factors. Gastrointestinal and reproductive tracts harbored a unique sub-population of CD4+ T cells co-expressing high levels of viral sensors which target several viral replication stages. This may reflect ongoing detection of viral components produced by the HIV reservoir. Gioia Cappelletti presented a study on the susceptibility of motoneurons to SARS-CoV-2 infection. This study was conducted using human iPSC-derived motoneurons. They were able to show that iPSC-motoneurons can be productively infected by SARS-CoV-2. This infection was accompanied by activation of antiviral and inflammatory responses.

Microbiota enhancing infection is a highly interesting finding raising several follow-up questions. The use of a T cell-specific HIV strain might be a limitation, which will be addressed. The developed germ-free BLT mouse model will be highly valuable for various future studies. Potential implications of this session were that shaping the microbiome could impact HIV infection, reversing damage in the gut could result in restriction of brain-inflammation and that potential tissue-specific replication of the viral reservoir could explain ongoing inflammation in those specific tissues. Finally, the susceptibility of moto-neurons for SARS-CoV-2 might unveil the basis for neuromuscular disorders during long-COVID.