# Analysis of the Interaction Between the Attenuated HSV-1 Strain M6 and Macrophages Indicates Its Potential as an Effective Vaccine Immunogen

## TL;DR

A weakened HSV-1 strain called M6 was found to cause a milder immune response and less tissue damage than the wild-type virus, suggesting it could be a safe and effective vaccine candidate.

## Contribution

The study demonstrates that the attenuated HSV-1 strain M6 induces a balanced immune response with reduced inflammation and tissue damage.

## Key findings

- The M6 strain infects macrophages via gD protein binding to HVEM receptor, similar to the wild-type strain.
- M6 induces lower inflammatory cytokines and immune signaling molecules compared to the wild-type strain.
- Mice infected with M6 showed milder pathological damage and more stable body weight than those infected with the wild-type strain.

## Abstract

Herpes simplex virus type 1 (HSV-1) is a very concerning pathogen due to its ability to persist in the host’s nervous system and continuously interfere with the immune system, which complicates treatment. Therefore, the development of an effective HSV-1 vaccine is crucial. In this study, we focused on an HSV-1 mutant strain, M6, which includes several deleted genes associated with viral infection virulence and latent infection function, and explored its infection of macrophages and immunological characteristics. The study found that both the attenuated strain M6 and the wild-type strain infect macrophages through the binding of the gD protein to the HVEM receptor on the macrophage surface. Compared to the wild-type strain, the attenuated M6 strain induced a milder immune response, characterized by the lower expression of immune signaling molecules and inflammatory cytokine levels. Upon reintroducing macrophages infected with the two strains into mice, the M6 strain induced lower levels of inflammatory cytokines and higher levels of chemokines in spleen cells and also slightly lower humoral and cellular immune responses than the wild-type strain. Further histopathological analysis revealed that mice in the attenuated M6 group showed more stable body weight changes and milder pathological damage in immune organs such as the liver, spleen, and lymph nodes. In conclusion, the attenuated M6 strain exhibits good immunogenicity and mild pathological side effects, suggesting its potential as an effective immunogen.