rabies antiserum

Transsynaptic viral tools in neural circuit analysis: from anatomical mapping to functional interrogation.

Boldogkői Zsolt Z, Torma Gábor G, Csabai Zsolt Z, Máté Zoltán Z et al.

The application of transsynaptic viruses has transformed neural circuit analysis, enabling increasingly precise mapping of neuronal connectivity. These approaches can be broadly divided into polysynaptic and monosynaptic strategies. Polysynaptic retrograde tracers based on pseudorabies virus, including the classically selected Bartha strain and genetically engineered retrograde variants have provided important insights into multisynaptic circuit organization in rodents. For polysynaptic anterograde tracing, herpes simplex virus strain H129 and its derivatives have been used to map output pathways, with later genetic modifications improving detectability and experimental control. Over the past few years, growing attention has shifted toward monosynaptic tracing based on engineered rabies virus platforms used in combination with adeno-associated virus helper systems, which enable genetically restricted spread to direct presynaptic partners. Viral tracing is increasingly integrated with functional approaches, including calcium and voltage imaging, optogenetics, chemogenetics, and recombinase-based genetic strategies, thereby extending circuit analysis from anatomical mapping to causal interrogation of the function of defined neuronal populations. Looking forward, improved control of polysynaptic spread, together with large transgene capacity, suitability for tracing hierarchical circuit architecture, and the ability to incorporate functional readouts, is expected to revive interest in multisynaptic tracing.

Antigen presentation by CD40+MHC-II+ astrocytes promotes CNS autoimmunity.

Lee Joon-Hyuk JH, Li Zhaorong Z, Soto Joselyn S JS, Kim Ah-Ram AR et al.

Astrocytes contribute to the pathology of multiple neurological disorders, including the T cell-driven autoimmune disease of the central nervous system (CNS) multiple sclerosis and its mouse model, experimental autoimmune encephalomyelitis1. However, little is known about functional interactions between astrocytes and CD4+ T cells. Here using rabies barcode interaction detection followed by sequencing2, in combination with single-cell RNA sequencing, in vitro co-culture systems and cell-specific in vivo CRISPR-Cas9-based genetic perturbation studies, we established that astrocytes expressing CD40 and MHC-II promote CNS T cell autoimmunity. We harnessed universal labelling immune partnerships by SorTagging intercellular contacts3 to analyse astrocyte-interacting CD4+ T cells, finding that direct astrocyte-CD4+ T cell interactions enhance pathogenic T helper 17 cell responses in experimental autoimmune encephalomyelitis. In addition, we studied the effect of these interactions on astrocytes. Using in vivo subproteomic approaches4 and AlphaFold-Multimer predictions5, we established that CD40 activation in astrocytes by CD40L expressed by CD4+ T cells induces the accumulation of PLIN4-positive lipid droplets, which provide acetyl-CoA to promote p65 acetylation-dependent NF-κB activation and antigen presentation. Finally, we detected CD40+MHC-II+LD+ astrocytes in multiple sclerosis samples by single-nucleus RNA sequencing and immunohistochemistry. In summary, these studies define a previously unrecognized mechanism by which astrocytes promote CNS autoimmunity.

Correction to "Rabies Virus-Inspired Metal-Organic Frameworks (MOFs) for Targeted Imaging and Chemotherapy of Glioma".

Augmented innate and humoral immune responses enhance early and durable rabies protection by a CD40L-overexpressing rabies vaccine.

Xing Xiao X, Wang Yufang Y, Xiong Zhimin Z, Liu Die D et al.

Rabies is the only acute zoonotic infectious disease with a mortality rate approaching 100%. Large-scale immunization of animals represents the most effective strategy for preventing human rabies. Consequently, there is a pressing need for a vaccine that is economical, safe, and efficient for controlling rabies transmitted by animals. A recombinant rabies virus (rLBNSE-CD40L) overexpressing murine CD40L was constructed using the RABV reverse genetics system. The possible adverse effects of rLBNSE-CD40L were evaluated using growth curves, body weight changes, survival rates, and inflammatory cell counts. The immunogenicity of rLBNSE-CD40L was assessed by measuring virus-neutralizing antibodies (VNA) levels, antiviral protection rates, and antibody isotype levels in mice. Flow cytometry, RNA sequencing, and lymph node immunofluorescence were employed to investigate the innate and humoral immune responses induced by rLBNSE-CD40L. Notably, rLBNSE-CD40L was found to rapidly generate significantly higher VNA levels as early as three days post-immunization, which relies on the activation of dendritic cells (DCs) and the engagement of innate immune-related pathways and genes. This vaccine candidate enhances innate immunity and elicits persistent primary and secondary antibody responses by promoting T helper 1 (Th1)-biased and T follicular helper (Tfh)-dependent germinal center (GC) humoral immunity. In conclusion, our study suggests that rLBNSE-CD40L has the potential to be developed into a non-pathogenic and effective animal rabies vaccine.