Abstract
Tripartite-motif 21 (TRIM21) is thought to regulate the type I interferon (IFN) response to virus pathogens and serve as a cytosolic Fc receptor for immunoglobulin. Since herpes simplex virus (HSV)-1 is sensitive to type I IFN and neutralizing antibody, we investigated the role of TRIM21 in response to ocular HSV-1 infection in mice. In comparison to wild type (WT) mice, TRIM21 deficient (TRIM21 KO) mice were found to be no more susceptible to ocular HSV-1 infection than WT animals, in terms of infectious virus recovered in the cornea. Similar pathology, in terms of neovascularization, opacity, and loss of peripheral vision function, was observed in both WT and TRIM21 KO mice. However, TRIM21 KO mice did possess a significant increase in infectious virus recovered in the trigeminal ganglia, in comparison to the WT animals. The increased susceptibility was not due to changes in HSV-1-specific CD4+ or CD8+ T cell numbers or functional capabilities, or in changes in type I IFN or IFN-inducible gene expression. In summary, the absence of TRIM21 results in a modest, but significant, increase in HSV-1 titers recovered from the TG of TRIM21 KO mice during acute infection, by a mechanism yet to be determined.
Highlights
Herpes simplex virus (HSV)-1 is a double-stranded DNA virus that elicits a robust inflammatory response following ocular infection in the naive mouse, often resulting in significant tissue pathology [1–3]
HSV-1, targets processes associated with the adaptive immune response, and interferes with a number of anti-viral pathways associated with the innate immune response [12], including oligoadenylate synthetase/RNase L and STING/p204/IFI16 pathways, thought to be important in controlling HSV-1 replication in the cornea of mice [13,14]
The results showed no deficiency in the number of total (Figure 7A,C) or HSV-1-specific CD4+ or CD8+ T cells (Figure 7B,C) residing in the trigeminal ganglia (TG) of HSV-1-infected Tripartite-motif 21 (TRIM21) KO mice compared to wild type (WT) or TRIM21+/− animals
Summary
Herpes simplex virus (HSV)-1 is a double-stranded DNA virus that elicits a robust inflammatory response following ocular infection in the naive mouse, often resulting in significant tissue pathology [1–3]. Responsible for the success of the pathogen are the countermeasures elicited by virus-encoded proteins that facilitate immune evasion or suppression. HSV-1-encoded glycoprotein (g)C, gE, and gI interfere with various aspects of antibody and complement action, including antibody-dependent cell cytotoxicity [6–8], whereas HSV-1-infected cell protein (ICP) blocks major histocompatibility complex (MHC) class I presentation of virus peptides to CD8+ cytotoxic T cells [9]. The overall success of an HSV-1 infection depends upon the status of the naive host relative to the type I IFN response [3], which is influenced by the site of initial infection, as well as the likelihood of a sufficient (duration) and broad antigen exposure, to achieve significant coverage by the adaptive immune system against virus-encoded products
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