OPTN-TBK1 axis and a role for PLK1 in HSV-1 infection

• Published in: mBio 2023-12, Vol.14 (6), p.e0271523
• Main Authors: Bhattacharya, Ilina, Volety, Ipsita, Shukla, Deepak
• Format: Article
• Language: English
• Subjects: Animals; antiviral defense; Autophagy; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; eye infection; Herpes Simplex - genetics; Herpes Simplex - metabolism; Herpes Simplex - virology; Herpesvirus 1, Human - genetics; Herpesvirus 1, Human - physiology; Host-Pathogen Interactions; HSV-1; Humans; Membrane Transport Proteins - genetics; Membrane Transport Proteins - metabolism; Mice; OPTN; Pathogenesis and Host Response; Phosphorylation; PLK1; Polo-Like Kinase 1; Protein Serine-Threonine Kinases - genetics; Protein Serine-Threonine Kinases - metabolism; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Research Article; TBK1; Transcription Factor TFIIIA - genetics; Transcription Factor TFIIIA - metabolism; Virus Latency
• ISSN: 2150-7511; 2150-7511
• DOI: 10.1128/mbio.02715-23

Herpes simplex virus type 1 (HSV-1) is globally prevalent, with latent infections observed in up to 80% of the population. The virus is known for subverting host defense mechanisms and infiltrating the nervous system to establish latency in peripheral ganglia. Multiple stressors can reactivate the virus, and recurrent herpes has been linked to vision loss and neurodegeneration. Identifying critical host factors that limit the spread of HSV-1 and the subsequent establishment of latent infection holds the potential to drive new intervention strategies for eradicating the virus. Numerous pieces of evidence underscore the significance of Tank-binding kinase 1 (TBK1) in restricting HSV-1. Reports have also suggested that phosphorylation of optineurin (OPTN) by TBK1 is required for triggering OPTN-mediated autophagy for HSV degradation. This report adds new insights into the roles of OPTN and TBK1 in HSV-1 infection and provides proof of a TBK1-independent HSV-1 restriction through OPTN. It confirms that TBK1 activation can be substituted by PLK1 to provide protection against HSV-1. In contrast, the activation of OPTN is likely an indispensable host defense mechanism for optimal defense against HSV-1.