Biology subjects

Bryer, A.

Publications and source records attributed to Bryer, A..

3 recordsLinked to original sources

bioRxiv2021

HIV-1 Mutants that Escape the Cytotoxic T-Lymphocytes are Defective in Viral DNA Integration

ABSTRACT HIV-1 replication is durably controlled in certain untreated HIV-1-infected individuals expressing particular human leukocyte antigens (HLA). These HLAs tag infected cells for elimination by presenting specific viral epitopes to CD8+ cytotoxic T-lymphocytes (CTL). In individuals expressing HLA-B27, CTLs primarily target the capsid protein (CA)-derived KK10 epitope. Selection of CA mutation R264K helps HIV-1 escape the CTL response but severely diminishes virus infectivity. Here we report that the R264K mutation-associated infectivity defect arises primarily from impaired viral DNA integration. Strikingly, selection of the compensatory CA mutation S173A or depletion of host cyclophilin A largely rescues the R264K-associated integration and infectivity defects. Collectively, our study reveals novel mechanistic insights into the fitness defect incurred by an HIV-1 variant escaping a CA-directed CTL response.

microbiology↗

bioRxiv2021

Full scale structural, mechanical and dynamical properties of HIV-1 liposomes.

Enveloped viruses are enclosed by a lipid membrane inside of which are all of the components necessary for the virus life cycle; viral proteins, the viral genome and metabolites. Viral envelopes are lipid bilayers that adopt morphologies ranging from spheres to tubes. The envelope is derived from the host cell during viral replication. Thus, the composition of the bilayer depends on the complex constitution of lipids from the host-cells organelle(s) where assembly and/or budding of the viral particle occurs. Here, molecular dynamics (MD) simulations of authentic, asymmetric HIV-1 liposomes are used to derive a unique level of resolution of its full-scale structure, mechanics and dynamics. Analysis of the structural properties reveal the distribution of thicknesses of the bilayers over the entire liposome as well as its global fluctuations. Moreover, full-scale mechanical analyses are employed to derive the global bending rigidity of HIV-1 liposomes. Finally, dynamical properties of the lipid molecules reveal important relationships between their 3D diffusion, the location of lipid-rafts and the asymmetrical composition of the envelope. Overall, our simulations reveal complex relationships between the rich lipid composition of the HIV-1 liposome and its structural, mechanical and dynamical properties with critical consequences to different stages of HIV-1s life cycle.

biophysics↗

bioRxiv2020

Accelerating Prediction of Chemical Shift of Protein Structures on GPUs

Experimental chemical shifts (CS) from solution and solid state magic-angle-spinning nuclear magnetic resonance spectra provide atomic level information for each amino acid within a protein or protein complex. However, structure determination of large complexes and assemblies based on NMR data alone remains challenging due the complexity of the calculations. Here, we present a hardware accelerated strategy for the estimation of NMR chemical-shifts of large macromolecular complexes based on the previously published PPM_One software. The original code was not viable for computing large complexes, with our largest dataset taking approximately 14 hours to complete. Our results show that the code refactoring and acceleration brought down the time taken of the software running on an NVIDIA V100 GPU to 46.71 seconds for our largest dataset of 11.3M atoms. We use OpenACC, a directive-based programming model for porting the application to a heterogeneous system consisting of x86 processors and NVIDIA GPUs. Finally, we demonstrate the feasibility of our approach in systems of increasing complexity ranging from 100K to 11.3M atoms. Author summary

biophysics↗