Abstract
Herpes simplex virus 1 (HSV-1) is a human pathogen capable of establishing lifelong latent infections that can reactivate under stress conditions. A viral immediate early protein that plays important roles in the HSV-1 lytic and latent infections is the viral E3 ubiquitin ligase, ICP0. ICP0 transactivates all temporal classes of HSV-1 genes and facilitates viral gene expression. ICP0 also impairs the antiviral effects of interferon (IFN)-b, a component of host innate defenses known to limit viral replication. To begin to understand how ICP0 allows HSV-1 to disarm the IFN-b response, we performed genetic analyses using a series of ICP0 truncation mutants in the absence and presence of IFN-b in cell culture. We observed that IFN-b pretreatment of cells significantly impaired the replication of the ICP0 truncation mutants, n212 and n312, which code for the first 211 and 311 amino acids of ICP0, respectively; this effect of IFN-b correlated with decreased HSV-1 early and late gene expression. This increased sensitivity to IFN-b was not as apparent with the ICP0 mutant, n389. Our mapping studies indicate that loss of 77 amino acids from residues 312 to 388 in the N-terminal half of ICP0 resulted in a virus that was significantly more sensitive to cells pre-exposed to IFN-b. This 77 amino acid region contains a phospho-SUMO-interacting motif or -SIM, which we propose participates in ICP0’s ability to counteract the antiviral response established by IFN-b.
Original language | English (US) |
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Journal | Microbiology Spectrum |
Volume | 10 |
Issue number | 4 |
DOIs | |
State | Published - Aug 2022 |
Externally published | Yes |
Keywords
- E3 ubiquitin ligase
- HSV-1
- ICP0
- herpes simplex virus
- innate immunity
- interferon-beta
- interferons
- viral gene expression
ASJC Scopus subject areas
- General Immunology and Microbiology
- Microbiology (medical)
- Infectious Diseases
- Genetics
- Physiology
- Cell Biology
- Ecology