Human herpesvirus 6B downregulates expression of activating ligands during lytic infection to escape elimination by natural killer cells

Dominik Schmiedel, Julie Tai, Francesca Levi-Schaffer, Sarah Dovrat, Ofer Mandelboim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

The Herpesviridae family consists of eight viruses, most of which infect a majority of the human population. One of the lessstudied members is human herpesvirus 6 (HHV-6) (Roseolovirus), which causes a mild, well-characterized childhood disease. Primary HHV-6 infection is followed by lifelong latency. Reactivation frequently occurs in immunocompromised patients, such as those suffering from HIV infection or cancer or following transplantation, and causes potentially life-threatening complications. In this study, we investigated the mechanisms that HHV-6 utilizes to remain undetected by natural killer (NK) cells, which are key participants in the innate immune response to infections. We revealed viral mechanisms which downregulate ligands for two powerful activating NK cell receptors: ULBP1, ULBP3, and MICB, which trigger NKG2D, and B7-H6, which activates NKp30. Accordingly, this downregulation impaired the ability of NK cells to recognize HHV-6-infected cells. Thus, we describe for the first time immune evasion mechanisms of HHV-6 that protect lytically infected cells from NK elimination.

Original languageAmerican English
Pages (from-to)9608-9617
Number of pages10
JournalJournal of Virology
Volume90
Issue number21
DOIs
StatePublished - 2016

Bibliographical note

Publisher Copyright:
© 2016, American Society for Microbiology.

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