Natural antibodies (Abs) can target host glycans on the surface of pathogens. We studied the evolution of glycan-reactive B cells of rhesus macaques and humans using glycosylated HIV-1 envelope (Env) as a model antigen. 2G12 is a broadly neutralizing Ab (bnAb) that targets a conserved glycan patch on Env of geographically diverse HIV-1 strains using a unique heavy-chain (VH) domain-swapped architecture that results in fragment antigen-binding (Fab) dimerization. Here, we describe HIV-1 Env Fab-dimerized glycan (FDG)-reactive bnAbs without VH-swapped domains from simian-human immunodeficiency virus (SHIV)-infected macaques. FDG Abs also recognized cell-surface glycans on diverse pathogens, including yeast and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike. FDG precursors were expanded by glycan-bearing immunogens in macaques and were abundant in HIV-1-naive humans. Moreover, FDG precursors were predominately mutated IgM+IgD+CD27+, thus suggesting that they originated from a pool of antigen-experienced IgM+ or marginal zone B cells.

• MeSH
• B-lymfocyty imunologie   MeSH
• COVID-19 imunologie   MeSH
• dimerizace MeSH
• epitopy imunologie   MeSH
• genové produkty env - virus lidské imunodeficience chemie   genetika   imunologie   MeSH
• glykoprotein S, koronavirus imunologie   MeSH
• glykosylace MeSH
• HIV infekce imunologie   MeSH
• HIV protilátky imunologie   MeSH
• HIV-1 imunologie   MeSH
• imunoglobuliny - Fab fragmenty chemie   imunologie   MeSH
• lidé MeSH
• Macaca mulatta MeSH
• neutralizující protilátky imunologie   MeSH
• polysacharidy chemie   imunologie   MeSH
• receptory antigenů B-buněk chemie   MeSH
• SARS-CoV-2 imunologie   MeSH
• široce neutralizující protilátky imunologie   MeSH
• vakcíny imunologie   MeSH
• virus opičí imunodeficience genetika   imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Lentiviruses are suitable to transfer potential therapeutic genes into non-replicating cells such as neurons, but systematic in vivo studies on transduction of neural cells within the complete brain are missing. We analysed the distribution of transduced cells with respect to brain structure, virus tropism, numbers of transduced neurons per brain, and influence of the Vpx or Vpr accessory proteins after injection of vectors based on SIVsmmPBj, HIV-2, and HIV-1 lentiviruses into the right striatum of the mouse brain. Transduced cells were found ipsilaterally around the injection canal, in corpus striatum and along corpus callosum, irrespective of the vector type. All vectors except HIV-2SEW transduced also single cells in the olfactory bulb, hippocampus, and cerebellum. Vector HIV-2SEW was the most neuron specific. However, vectors PBjSEW and HIV-1SEW transduced more neurons per brain (means 41,299 and 32,309) than HIV-2SEW (16,102). In the presence of Vpx/Vpr proteins, HIV-2SEW(Vpx) and HIV-1SEW(Vpr) showed higher overall transduction efficiencies (30,696 and 27,947 neurons per brain) than PBjSEW(Vpx) (6636). The distances of transduced cells from the injection canal did not differ among the viruses but correlated positively with the numbers of transduced neurons. The presence of Vpx/Vpr did not increase the numbers of transduced neurons. Parental virus type and the vector equipment seem to influence cellular tropism and transduction efficiency. Thus, precision of injection and choice of virus pseudotype are not sufficient when targeted lentiviral vector transduction of a defined brain cell population is required.

• MeSH
• genetické vektory aplikace a dávkování   genetika   farmakokinetika   MeSH
• HIV-1 genetika   metabolismus   MeSH
• HIV-2 genetika   metabolismus   MeSH
• kultivované buňky MeSH
• kvalitativní výzkum MeSH
• Lentivirus genetika   metabolismus   MeSH
• mozek metabolismus   virologie   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• těhotenství MeSH
• transdukce genetická metody   MeSH
• tropismus virů * MeSH
• virus opičí imunodeficience genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH