Tetraspanin CD81 regulates HSV-1 infection

• Type of Material: Article
• Authors: Beatriz Benayas, Universidad Autónoma de Madrid; Isabel Sastre, Universidad Autónoma de Madrid; Soraya Lopez-Martin, Universidad Autónoma de Madrid; Adrian Oo, Emory University; Baek Kim, Emory University; Maria J. Bullido, Universidad Autónoma de Madrid; Jesus Aldudo, Universidad Autónoma de Madrid; Maria Yanez-Mo, Universidad Autónoma de Madrid
• Language: English
• Date: 2020-06-04
• Publisher: Springer
• Publication Version: Final Published Version
• Copyright Statement: © Springer-Verlag GmbH Germany, part of Springer Nature 2020.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1007/s00430-020-00684-0
• Title of Journal or Parent Work: Medical Microbiology and Immunology
• Volume: 209
• Issue: 4
• Start Page: 489
• End Page: 498
• Grant/Funding Information: This work has been supported by grants BIO2017-86500-R from Ministerio Español de Economía y Competitividad (MINECO) to MY-M and SAF2017-85747-R to MJB as well as USA NIH R01 AI136581 and AI150451 to BK.; BB was supported by a predoctoral contract from Garantía Juvenil CAM program.; The institutional grants of Fundación Ramón Areces and Banco de Santander to the Centro de Biología Molecular Severo Ochoa are gratefully acknowledged.
• Keywords: SAMHD1 restricts; Membrane; Replication; Life Sciences & Biomedicine; Viral replication; CD9; Inhibition; Immunology; Microbiology; Tetraspanin; Cell cycle; Simplex virus type 1; SAMHD1; Herpes simplex-1; CD81; Science & Technology
• Research Categories: Health Sciences, Immunology; Biology, Cell; Biology, Microbiology

Abstract

Different members of the tetraspanin superfamily have been described to regulate different virus infectious cycles at several stages: viral entry, viral replication or virion exit or infectivity. In addition, tetraspanin CD81 regulates HIV reverse transcription through its association with the dNTP hydrolase SAMHD1. Here we aimed at analysing the role of CD81 in Herpes simplex virus 1 infectivity using a neuroblastoma cell model. For this purpose, we generated a CD81 KO cell line using the CRISPR/Cas9 technology. Despite being CD81 a plasma membrane protein, CD81 KO cells showed no defects in viral entry nor in the expression of early protein markers. In contrast, glycoprotein B and C, which require viral DNA replication for their expression, were significantly reduced in CD81 KO infected cells. Indeed, HSV-1 DNA replication and the formation of new infectious particles were severely compromised in CD81 KO cells. We could not detect significant changes in SAMHD1 total expression levels, but a relocalization into endosomal structures was observed in CD81 KO cells. In summary, CD81 KO cells showed impaired viral DNA replication and produced greatly diminished viral titers.