PMID- 32994323
OWN - NLM
STAT- MEDLINE
DCOM- 20210720
LR  - 20210720
IS  - 2150-7511 (Electronic)
VI  - 11
IP  - 5
DP  - 2020 Sep 29
TI  - Human Cytomegalovirus Envelope Protein gpUL132 Regulates Infectious Virus 
      Production through Formation of the Viral Assembly Compartment.
LID - 10.1128/mBio.02044-20 [doi]
LID - e02044-20
AB  - The human cytomegalovirus (HCMV) UL132 open reading frame encodes a 
      270-amino-acid type I envelope glycoprotein, gpUL132. The deletion of UL132 
      (DeltaUL132) from the HCMV genome results in a pronounced deficit in virus yield, 
      with an approximately 2-log decrease in the production of infectious virus 
      compared to the wild-type (WT) virus. Characterization of the DeltaUL132 mutant virus 
      indicated that it was less infectious with a high particle-to-infectious unit 
      ratio and an altered composition of virion proteins compared to the WT virus. In 
      addition, the viral assembly compartment (AC) failed to form in cells infected 
      with the DeltaUL132 mutant virus. The expression of gpUL132 in trans rescued the 
      defects in the morphogenesis of the AC in cells infected with the DeltaUL132 mutant 
      virus and in infectious virus production. Furthermore, using cell lines 
      expressing chimeric proteins, we demonstrated that the cytosolic domain of 
      gpUL132 was sufficient to rescue AC formation and WT levels of virus production. 
      Progeny virions from DeltaUL132-infected cells expressing the cytosolic domain of 
      gpUL132 exhibited particle-to-infectious unit ratios similar to those of the WT 
      virus. Together, our findings argue that gpUL132 is essential for HCMV AC 
      formation and the efficient production of infectious particles, thus highlighting 
      the importance of this envelope protein for the virus-induced reorganization of 
      intracellular membranes and AC formation in the assembly of infectious 
      virus.IMPORTANCE Following infection of permissive cells, human cytomegalovirus 
      (HCMV) induces the reorganization of intracellular membranes resulting in the 
      formation of a distinctive membranous compartment in the cytoplasm of infected 
      cells. This compartment has been designated the viral assembly compartment (AC) 
      and is thought to be a site for cytoplasmic virion assembly and envelopment. In 
      this study, we have demonstrated that a single virion envelope glycoprotein is 
      essential for AC formation in infected cells, and in its absence, there is a 
      significant decrease in the production of infectious virions. These findings are 
      consistent with those from other studies that have demonstrated the importance of 
      host cell proteins in the formation of the AC and demonstrate a critical role of 
      a single virion protein in AC formation and the efficient assembly of infectious 
      virus.
CI  - Copyright (c) 2020 Wu et al.
FAU - Wu, Hui
AU  - Wu H
AD  - Department of Microbiology, School of Medicine, University of Alabama in 
      Birmingham, Birmingham, Alabama, USA.
FAU - Kropff, Barbara
AU  - Kropff B
AD  - Virologisches Institut, Klinische und Molekulare Virologie, 
      Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Germany.
FAU - Mach, Michael
AU  - Mach M
AD  - Virologisches Institut, Klinische und Molekulare Virologie, 
      Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Germany.
FAU - Britt, William J
AU  - Britt WJ
AD  - Department of Microbiology, School of Medicine, University of Alabama in 
      Birmingham, Birmingham, Alabama, USA Wbritt@peds.uab.edu.
AD  - Department of Pediatrics, University of Alabama in Birmingham School of Medicine, 
      Birmingham, Alabama, USA.
LA  - eng
GR  - R01 AI035602/AI/NIAID NIH HHS/United States
GR  - R01 AI120619/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20200929
PL  - United States
TA  - mBio
JT  - mBio
JID - 101519231
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Viral Envelope Proteins)
RN  - 0 (Viral Proteins)
RN  - 0 (gpUL132 protein, human cytomegalovirus)
SB  - IM
MH  - Cell Line
MH  - Cells, Cultured
MH  - Cytomegalovirus/*genetics/*physiology
MH  - Fibroblasts/virology
MH  - Foreskin/cytology
MH  - *Gene Expression Regulation, Viral
MH  - Humans
MH  - Male
MH  - Membrane Glycoproteins/*genetics
MH  - Viral Envelope Proteins/*genetics
MH  - Viral Proteins/metabolism
MH  - Virion/genetics
MH  - *Virus Assembly
PMC - PMC7527726
OTO - NOTNLM
OT  - human cytomegalovirus
OT  - viral assembly compartment
OT  - virion envelope protein
OT  - virus glycoproteins
EDAT- 2020/10/01 06:00
MHDA- 2021/07/21 06:00
PMCR- 2020/09/29
CRDT- 2020/09/30 06:06
PHST- 2020/09/30 06:06 [entrez]
PHST- 2020/10/01 06:00 [pubmed]
PHST- 2021/07/21 06:00 [medline]
PHST- 2020/09/29 00:00 [pmc-release]
AID - mBio.02044-20 [pii]
AID - mBio02044-20 [pii]
AID - 10.1128/mBio.02044-20 [doi]
PST - epublish
SO  - mBio. 2020 Sep 29;11(5):e02044-20. doi: 10.1128/mBio.02044-20.