Biology subjects

Anderson, F.

Publications and source records attributed to Anderson, F..

3 recordsLinked to original sources

bioRxiv2022

The interferon-inducible GTPase MxB promotes capsid disassembly and genome release of herpesviruses

Host proteins sense viral products and induce defence mechanisms, particularly in immune cells. Using cell-free assays and quantitative mass spectrometry, we determined the interactome of capsid- host protein complexes of herpes simplex virus and identified the large dynamin-like GTPase myxovirus resistance protein B (MxB) as an interferon-inducible protein interacting with capsids. Electron microscopy analyses showed that cytosols containing MxB had the remarkable capability to disassemble the icosahedral capsids of herpes simplex viruses and varicella zoster virus into flat sheets of connected triangular faces. In contrast, capsids remained intact in cytosols with MxB mutants unable to hydrolyse GTP or to dimerize. Our data suggest that MxB senses herpesviral capsids, mediates their disassembly, and thereby restricts the efficiency of nuclear targeting of incoming capsids and/or the assembly of progeny capsids. The resulting premature release of viral genomes from capsids may enhance the activation of DNA sensors, and thereby amplify the innate immune responses.

microbiology↗

bioRxiv2021

HIV-specific CD8+ T-cells in tonsils express exhaustive TRM-like signatures

Lymphoid tissues are an important HIV reservoir site that persists in the face of antiretroviral therapy and natural immunity. Targeting these reservoirs by harnessing the antiviral activity of local tissue resident memory ( TRM) CD8+ T-cells is of great interest, but limited data exist on TRMs within lymph nodes of people living with HIV (PLWH). Here, we studied tonsil CD8+ T-cells obtained from PLWH and uninfected controls from South Africa. We show that these cells are preferentially located outside the germinal centers (GCs), the main reservoir site for HIV, and display a low cytolytic and transcriptionally TRM-like profile that is distinct from blood. In PLWH, CD8+ TRM-like cells are highly expanded and adopt a more cytolytic, activated and exhausted phenotype characterized by increased expression of CD69, PD-1 and perforin, but reduced CD127. This phenotype was enhanced in HIV-specific CD8+ T-cells from tonsils compared to matched blood. Single-cell profiling of these cells revealed a clear transcriptional signature of T-cell activation, clonal expansion and exhaustion ex-vivo. In contrast, this signature was absent from HIV-specific CD8+ T-cells in tonsils isolated from a natural HIV controller, who expressed lower levels of cell surface PD-1 and CXCR5, and reduced transcriptional evidence of T-cell activation, exhaustion and cytolytic activity. Thus, we show that HIV-specific TRM-like CD8+ T-cells in tonsils from non-HIV controllers are enriched for activation and exhaustion profiles compared to those in blood, suggesting that lymphoid HIV-specific CD8+ TRM cells are potentially ideal candidates for immunotherapy to modulate their ability to targeting the HIV reservoirs.

immunology↗

bioRxiv2021

riboviz 2: A flexible and robust ribosome profiling data analysis and visualization workflow

MotivationRibosome profiling, or Ribo-seq, is the state of the art method for quantifying protein synthesis in living cells. Computational analysis of Ribo-seq data remains challenging due to the complexity of the procedure, as well as variations introduced for specific organisms or specialized analyses. Many bioinformatic pipelines have been developed, but these pipelines have key limitations in terms of functionality or usability. ResultsWe present riboviz 2, an updated riboviz package, for the comprehensive transcript-centric analysis and visualization of Ribo-seq data. riboviz 2 includes an analysis workflow built on the Nextflow workflow management system, combining freely available software with custom code. The package is extensively documented and provides example configuration files for organisms spanning the domains of life. riboviz 2 is distinguished by clear separation of concerns between annotation and analysis: prior to a run, the user chooses a transcriptome in FASTA format, paired with annotation for the CDS locations in GFF3 format. The user is empowered to choose the relevant transcriptome for their biological question, or to run alternative analyses that address distinct questions. riboviz 2 has been extensively tested on various library preparation strategies, including multiplexed samples. riboviz 2 is flexible and uses open, documented file formats, allowing users to integrate new analyses with the pipeline. Availabilityriboviz 2 is freely available at github.com/riboviz/riboviz. Supplementary information

bioinformatics↗