| First Author | Tongmuang N | Year | 2024 |
| Journal | Vaccines (Basel) | Volume | 12 |
| Issue | 8 | PubMed ID | 39203963 |
| Mgi Jnum | J:358078 | Mgi Id | MGI:7764568 |
| Doi | 10.3390/vaccines12080837 | Citation | Tongmuang N, et al. (2024) UL56 Is Essential for Herpes Simplex Virus-1 Virulence In Vivo but Is Dispensable for Induction of Host-Protective Immunity. Vaccines (Basel) 12(8) |
| abstractText | Herpes simplex virus-1 (HSV-1) is common and can cause significant disease in humans. Unfortunately, efforts to develop effective vaccines against HSV-1 have so far failed. A detailed understanding of how the virus infects its host and how the host mounts potent immune responses against the virus may inform new vaccine approaches. Here, using a zosteriform mouse model, we examined how the HSV-1 gene UL56 affects the ability of the virus to cause morbidity and generate protective immunity. A UL56 deletion mutant, DeltaUL56, was derived from the wild-type HSV-1 strain SC16, alongside a revertant strain in which UL56 was reintroduced in DeltaUL56. In vitro, the three virus strains replicated in a similar manner; however, in vivo, only the wild type and the revertant strains caused shingles-like skin lesions and death. Mice previously infected with DeltaUL56 became resistant to a lethal challenge with the wild-type SC16. The protective immunity induced by DeltaUL56 was independent of IL-1, IL-33, and IL-36 signaling through IL-1RAP. Both skin and intramuscular DeltaUL56 inoculation generated protective immunity against a lethal SC16 challenge. After 6 months, female mice remained resistant to infection, while male mice exhibited signs of declining protection. Our data demonstrate that UL56 is important for the ability of HSV-1 to spread within the infected host and that a UL56 strain elicits an effective immune response against HSV-1 despite this loss of virulence. These findings may guide further HSV-1 vaccine development. |
