PMID- 27535049
OWN - NLM
STAT- MEDLINE
DCOM- 20170505
LR  - 20190321
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 90
IP  - 21
DP  - 2016 Nov 1
TI  - Human Herpesvirus 6B Downregulates Expression of Activating Ligands during Lytic 
      Infection To Escape Elimination by Natural Killer Cells.
PG  - 9608-9617
LID - 10.1128/JVI.01164-16 [doi]
AB  - The Herpesviridae family consists of eight viruses, most of which infect a 
      majority of the human population. One of the less-studied 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. IMPORTANCE: Human herpesvirus 6 (HHV-6) latently infects a large 
      portion of the human population and can reactivate in humans lacking a functional 
      immune system, such as cancer or AIDS patients. Under these conditions, it can 
      cause life-threatening diseases. To date, the actions and interplay of immune 
      cells, and particularly cells of the innate immune system, during HHV-6 infection 
      are poorly defined. In this study, we aimed to understand how cells undergoing 
      lytic HHV-6 infection interact with natural killer (NK) cells, innate lymphocytes 
      constituting the first line of defense against viral intruders. We show that 
      HHV-6 suppresses the expression of surface proteins that alert the immune cells 
      by triggering two major receptors on NK cells, NKG2D and NKp30. As a consequence, 
      HHV-6 can replicate undetected by the innate immune system and potentially spread 
      infection throughout the body. This study advances the understanding of HHV-6 
      biology and the measures it uses to successfully escape immune elimination.
CI  - Copyright (c) 2016, American Society for Microbiology. All Rights Reserved.
FAU - Schmiedel, Dominik
AU  - Schmiedel D
AD  - Lautenberg Center for General and Tumor Immunology, BioMedical Research Institute 
      Israel-Canada, Faculty of Medicine, The Hebrew University Hadassah Medical 
      School, Jerusalem, Israel.
FAU - Tai, Julie
AU  - Tai J
AD  - Lautenberg Center for General and Tumor Immunology, BioMedical Research Institute 
      Israel-Canada, Faculty of Medicine, The Hebrew University Hadassah Medical 
      School, Jerusalem, Israel.
FAU - Levi-Schaffer, Francesca
AU  - Levi-Schaffer F
AD  - Pharmacology and Experimental Therapeutics Unit, Institute of Drug Research, 
      School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, 
      Jerusalem, Israel.
FAU - Dovrat, Sarah
AU  - Dovrat S
AD  - Central Virology Laboratory, Chaim Sheba Medical Center, Ramat-Gan, Israel.
FAU - Mandelboim, Ofer
AU  - Mandelboim O
AD  - Lautenberg Center for General and Tumor Immunology, BioMedical Research Institute 
      Israel-Canada, Faculty of Medicine, The Hebrew University Hadassah Medical 
      School, Jerusalem, Israel oferm@ekmd.huji.ac.il.
LA  - eng
PT  - Journal Article
DEP - 20161014
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Ligands)
RN  - 0 (Receptors, Natural Killer Cell)
SB  - IM
MH  - Cell Line
MH  - Down-Regulation/*immunology
MH  - HIV Infections/immunology
MH  - Herpesviridae Infections/*immunology
MH  - Herpesvirus 6, Human/*immunology
MH  - Humans
MH  - Immune Evasion/immunology
MH  - Immunity, Innate/immunology
MH  - Killer Cells, Natural/*immunology
MH  - Ligands
MH  - Receptors, Natural Killer Cell/immunology
MH  - Virus Physiological Phenomena/immunology
PMC - PMC5068514
EDAT- 2016/08/19 06:00
MHDA- 2017/05/06 06:00
PMCR- 2017/04/14
CRDT- 2016/08/19 06:00
PHST- 2016/06/15 00:00 [received]
PHST- 2016/08/03 00:00 [accepted]
PHST- 2016/08/19 06:00 [pubmed]
PHST- 2017/05/06 06:00 [medline]
PHST- 2016/08/19 06:00 [entrez]
PHST- 2017/04/14 00:00 [pmc-release]
AID - JVI.01164-16 [pii]
AID - 01164-16 [pii]
AID - 10.1128/JVI.01164-16 [doi]
PST - epublish
SO  - J Virol. 2016 Oct 14;90(21):9608-9617. doi: 10.1128/JVI.01164-16. Print 2016 Nov 
      1.