HSV1 MicroRNA Modulation of GPI Anchoring and Downstream Immune Evasion
نویسندگان
چکیده
Herpes simplex virus 1 (HSV1) is a ubiquitous human pathogen that utilizes variable mechanisms to evade immune surveillance. The glycosylphosphatidylinositol (GPI) anchoring pathway is a multistep process in which a myriad of different proteins are covalently attached to a GPI moiety to be presented on the cell surface. Among the different GPI-anchored proteins there are many with immunological importance. We present evidence that the HSV1-encoded miR H8 directly targets PIGT, a member of the protein complex that covalently attaches proteins to GPI in the final step of GPI anchoring. This results in a membrane down-modulation of several different immune-related, GPI-anchored proteins, including ligands for natural killer-activating receptors and the prominent viral restriction factor tetherin. Thus, we suggest that by utilizing just one of dozens of miRNAs encoded by HSV1, the virus can counteract the host immune response at several key points.
منابع مشابه
Herpes Simplex Virus Type 1 Infection of Activated Cytotoxic T Cells
Herpes simplex virus type 1 (HSV1), a large DNA-containing virus, is endemic in all human populations investigated. After infection of mucocutaneous surfaces, HSV1 establishes a latent infection in nerve cells. Recently, it was demonstrated that HSV1 can also infect activated T lymphocytes. However, the consequences of T cell infection for viral pathogenesis and immunity are unknown. We have ob...
متن کاملPrediction of Ebolavirus Genomes Encoded MicroRNA- Like Small RNAs Using Bioinformatics Approaches
Recent findings revealed that certain viruses encoded microRNA-like small RNAs using the RNA interference machinery in the host cells. However, the function of these virusencoded microRNA-like small RNAs remained unclear, and whether these microRNAlike small RNAs were involved in the replication of the virus and viral infection was still disputable. In this chapter, the negative-sense RNA genom...
متن کاملEstablishment of HSV1 Latency in Immunodeficient Mice Facilitates Efficient In Vivo Reactivation
The establishment of latent infections in sensory neurons is a remarkably effective immune evasion strategy that accounts for the widespread dissemination of life long Herpes Simplex Virus type 1 (HSV1) infections in humans. Periodic reactivation of latent virus results in asymptomatic shedding and transmission of HSV1 or recurrent disease that is usually mild but can be severe. An in-depth und...
متن کاملGPI-Anchored Fibromodulin as a Novel Target in Chronic Lymphocytic Leukemia: Diagnostic and Therapeutic Implications
Background: We have previously reported the aberrant expression of Fibromodulin (FMOD) in patients with chronic lymphocytic leukemia (CLL). Although FMOD has been considered as a cytoplasmic or secretory protein, we discovered the cell surface expression of FMOD in leukemic B cells via anchoring with glycosylphosphatidylinositol (GPI). Objective: To evaluate FM...
متن کاملA GPI anchor explains the unique biological features of the common NKG2D-ligand allele MICA*008.
The human MICA (MHC I-related chain A) gene, encoding a ligand for the NKG2D (NKG2-D type II integral membrane protein) receptor, is highly polymorphic. A group of MICA alleles, named MICA 5.1 (prototype, MICA*008), produce a truncated protein due to a nucleotide insertion in the transmembrane domain. These alleles are very frequent in all of the human populations studied and they have differen...
متن کامل