PMID- 36688652
OWN - NLM
STAT- MEDLINE
DCOM- 20230307
LR  - 20230724
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 97
IP  - 2
DP  - 2023 Feb 28
TI  - Characterization of the HHV-6B U20 Immunoevasin.
PG  - e0189022
LID - 10.1128/jvi.01890-22 [doi]
LID - e01890-22
AB  - Roseoloviruses (human herpesvirus 6A [HHV-6A], -6B, and -7) infect >90% of the 
      human population during early childhood and are thought to remain latent or 
      persistent throughout the life of the host. As such, these viruses are among the 
      most pervasive and stealthy of all viruses; they must necessarily excel at 
      escaping immune detection throughout the life of the host, and yet, very little 
      is known about how these viruses so successfully escape host defenses. Here, we 
      characterize the expression, trafficking, and posttranslational modifications of 
      the HHV6B U20 gene product, which is encoded within a block of genes unique to 
      the roseoloviruses. HHV-6B U20 trafficked slowly through the secretory system, 
      receiving several posttranslational modifications to its N-linked glycans, 
      indicative of surface-expressed glycoproteins, and eventually reaching the cell 
      surface before being internalized. Interestingly, U20 is also phosphorylated on 
      at least one Ser, Thr, or Tyr residue. These results provide a framework to 
      understand the role(s) of U20 in evading host defenses. IMPORTANCE The 
      roseolovirus U20 proteins are virus-encoded integral membrane glycoproteins 
      possessing class I major histocompatibility complex (MHC)-like folds. 
      Surprisingly, although U20 proteins from HHV-6A and -6B share 92% identity, 
      recent studies ascribe different functions to HHV6A U20 and HHV6B U20. HHV6A U20 
      was shown to downregulate NKG2D ligands, while HHV6B U20 was shown to inhibit 
      tumor necrosis factor alpha (TNF-alpha)-induced apoptosis during nonproductive 
      infection with HHV6B (E. Kofod-Olsen, K. Ross-Hansen, M. H. Schleimann, D. K. 
      Jensen, et al., J Virol 86:11483-11492, 2012, 
      https://doi.org/10.1128/jvi.00847-12; A. E. Chaouat, B. Seliger, O. Mandelboim, 
      D. Schmiedel, Front Immunol 12:714799, 2021, 
      https://doi.org/10.3389/fimmu.2021.714799). Here, we have performed cell 
      biological and biochemical characterization of the trafficking, glycosylation, 
      and posttranslational modifications occurring on HHV6B U20.
FAU - Schneider, Christine L
AU  - Schneider CL
AD  - Department of Microbiology and Immunology, Medical College of Wisconsin, 
      Milwaukee, Wisconsin, USA.
FAU - Whyte, Melissa L
AU  - Whyte ML
AD  - Department of Microbiology and Immunology, Medical College of Wisconsin, 
      Milwaukee, Wisconsin, USA.
FAU - Konrad, Sheryl L
AU  - Konrad SL
AD  - Department of Microbiology and Immunology, Medical College of Wisconsin, 
      Milwaukee, Wisconsin, USA.
FAU - Hudson, Amy W
AU  - Hudson AW
AUID- ORCID: 0000-0001-9718-6910
AD  - Department of Microbiology and Immunology, Medical College of Wisconsin, 
      Milwaukee, Wisconsin, USA.
LA  - eng
GR  - R01 GM120735/GM/NIGMS NIH HHS/United States
GR  - R21 AI076722/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20230123
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Viral Proteins)
SB  - IM
MH  - Humans
MH  - Herpesvirus 6, Human/genetics/immunology
MH  - *Membrane Glycoproteins/genetics/metabolism
MH  - *Roseolovirus Infections/immunology/virology
MH  - *Viral Proteins/genetics/immunology
MH  - Immune Evasion
PMC - PMC9973003
OTO - NOTNLM
OT  - HHV-6A
OT  - HHV-6B
OT  - HHV-7
OT  - U20
OT  - herpesviruses
OT  - human herpesviruses
OT  - immune evasion
COIS- The authors declare no conflict of interest.
EDAT- 2023/01/24 06:00
MHDA- 2023/03/03 06:00
PMCR- 2023/07/23
CRDT- 2023/01/23 09:04
PHST- 2023/01/24 06:00 [pubmed]
PHST- 2023/03/03 06:00 [medline]
PHST- 2023/01/23 09:04 [entrez]
PHST- 2023/07/23 00:00 [pmc-release]
AID - 01890-22 [pii]
AID - jvi.01890-22 [pii]
AID - 10.1128/jvi.01890-22 [doi]
PST - ppublish
SO  - J Virol. 2023 Feb 28;97(2):e0189022. doi: 10.1128/jvi.01890-22. Epub 2023 Jan 23.