# A comparative analysis of the dendritic cell response upon exposure to different rabies virus strains

## TL;DR

This study explores how different rabies virus strains affect dendritic cells, revealing that most strains do not trigger a strong immune response, which may explain the virus's high fatality rate.

## Contribution

The study compares the in vitro effects of three rabies virus strains on dendritic cell activation and infection, highlighting strain-specific differences.

## Key findings

- Two rabies virus strains infected a small proportion of dendritic cells, leading to minor activation.
- Exposure to any rabies virus strain did not suppress dendritic cell responsiveness or induce a strong antiviral state.
- Dendritic cells retained their ability to respond to additional stimuli despite virus exposure.

## Abstract

Rabies is a viral zoonotic disease that causes over 60,000 human deaths annually worldwide. Natural infections lack a virus-specific immune response, leading to a near 100% fatality rate unless immediately treated. Rabies virus (RABV) is typically transmitted through bites from rabid dogs or other carnivores to humans and may initially interact with innate immune cells such as dendritic cells at the site of infection. This study investigates the in vitro response of human monocyte-derived dendritic cells (moDCs) exposed to two pathogenic RABV strains—silver-haired bat rabies virus (SHBRV) and dog-related rabies virus (dogRV)—and an attenuated vaccine strain (SAD P5). MoDCs were susceptible only to high doses of SHBRV and SAD P5, resulting in a more mature and migratory phenotype within the infected moDC populations. No infection was observed in moDCs exposed to dogRV. In co-culture with T cells, the presence of RABV-exposed moDCs, regardless of the strain, did not enhance T cell activation. Additionally, RABV exposure did not hinder LPS-induced moDC maturation; instead, high doses of SHBRV and SAD P5 even boosted activation levels. Overall, the findings suggest varied capabilities of RABV strains to infect and activate moDCs in vitro. However, exposure to any RABV strain did not provoke a clear antiviral state or suppression of moDC responsiveness. This lack of activation may contribute to the absence of an effective adaptive immune response in natural RABV infections.

Rabies virus infections in humans are almost always fatal if left untreated due to a lack of a protective immune response. Dendritic cells play a crucial role in initiating an antiviral immune response, so our study investigated their response to exposure to three different rabies virus strains. We discovered that two of the three strains could infect a small proportion of dendritic cells. The third strain did not activate the cells, while exposure to the other two strains led to only minor signs of activation. This response was insufficient to trigger a significant immune reaction. Despite exposure to the virus, the dendritic cells retained their ability to respond to additional stimuli. Our findings provide insight into how rabies virus interacts with a crucial part of the initial immune response and highlight the need for further research into boosting immune activation by targeting dendritic cells.