The Roseoloviruses Downregulate the Protein Tyrosine Phosphatase PTPRC (CD45). J Virol 2021 Jun 24;95(14):e0162820
Date
05/07/2021Pubmed ID
33952641Pubmed Central ID
PMC8223955DOI
10.1128/JVI.01628-20Scopus ID
2-s2.0-85108871238 (requires institutional sign-in at Scopus site) 6 CitationsAbstract
Like all herpesviruses, the roseoloviruses (HHV6A, -6B, and -7) establish lifelong infection within their host, requiring these viruses to evade host antiviral responses. One common host-evasion strategy is the downregulation of host-encoded, surface-expressed glycoproteins. Roseoloviruses have been shown to evade the host immune response by downregulating NK-activating ligands, class I MHC, and the TCR/CD3 complex. To more globally identify glycoproteins that are differentially expressed on the surface of HHV6A-infected cells, we performed cell surface capture of N-linked glycoproteins present on the surface of T cells infected with HHV6A, and compared these to proteins present on the surface of uninfected T cells. We found that the protein tyrosine phosphatase CD45 is downregulated in T cells infected with HHV6A. We also demonstrated that CD45 is similarly downregulated in cells infected with HHV7. CD45 is essential for signaling through the T cell receptor and, as such, is necessary for developing a fully functional immune response. Interestingly, the closely related betaherpesviruses human cytomegalovirus (HCMV) and murine cytomegalovirus (MCMV) have also separately evolved unique mechanisms to target CD45. While HCMV and MCMV target CD45 signaling and trafficking, HHV6A acts to downregulate CD45 transcripts. IMPORTANCE Human herpesviruses-6 and -7 infect essentially 100% of the world's population before the age of 5 and then remain latent or persistent in their host throughout life. As such, these viruses are among the most pervasive and stealthy of all viruses. Host immune cells rely on the presence of surface-expressed proteins to identify and target virus-infected cells. Here, we investigated the changes that occur to proteins expressed on the cell surface of T cells after infection with human herpesvirus-6A. We discovered that HHV-6A infection results in a reduction of CD45 on the surface of infected T cells and impaired activation in response to T cell receptor stimulation.
Author List
Whyte ML, Smith KA, Buchberger A, Berg Luecke L, Tjan LH, Mori Y, Gundry RL, Hudson AWAuthor
Amy W. Hudson PhD Professor in the Microbiology and Immunology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Cell LineDown-Regulation
Gene Expression Regulation, Enzymologic
Gene Expression Regulation, Viral
HEK293 Cells
Herpesvirus 6, Human
Herpesvirus 7, Human
Humans
Leukocyte Common Antigens
Protein Stability
Receptors, Antigen, T-Cell
T-Lymphocytes
