PMID- 32075937
OWN - NLM
STAT- MEDLINE
DCOM- 20201019
LR  - 20210110
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 94
IP  - 9
DP  - 2020 Apr 16
TI  - Identification of Host Trafficking Genes Required for HIV-1 Virological Synapse 
      Formation in Dendritic Cells.
LID - 10.1128/JVI.01597-19 [doi]
LID - e01597-19
AB  - Dendritic cells (DCs) are one of the earliest targets of HIV-1 infection acting 
      as a "Trojan horse," concealing the virus from the innate immune system and 
      delivering it to T cells via virological synapses (VS). To explicate how the 
      virus is trafficked through the cell to the VS and evades degradation, a 
      high-throughput small interfering RNA screen targeting membrane trafficking 
      proteins was performed in monocyte-derived DCs. We identified several proteins 
      including BIN-1 and RAB7L1 that share common roles in transport from endosomal 
      compartments. Depletion of target proteins resulted in an accumulation of virus 
      in intracellular compartments and significantly reduced viral trans-infection via 
      the VS. By targeting endocytic trafficking and retromer recycling to the plasma 
      membrane, we were able to reduce the virus's ability to accumulate at budding 
      microdomains and the VS. Thus, we identify key genes involved in a pathway within 
      DCs that is exploited by HIV-1 to traffic to the VS.IMPORTANCE The lentivirus 
      human immunodeficiency virus (HIV) targets and destroys CD4(+) T cells, leaving 
      the host vulnerable to life-threatening opportunistic infections associated with 
      AIDS. Dendritic cells (DCs) form a virological synapse (VS) with CD4(+) T cells, 
      enabling the efficient transfer of virus between the two cells. We have 
      identified cellular factors that are critical in the induction of the VS. We show 
      that ADP-ribosylation factor 1 (ARF1), bridging integrator 1 (BIN1), and Rab 
      GTPases RAB7L1 and RAB8A are important regulators of HIV-1 trafficking to the VS 
      and therefore the infection of CD4(+) T cells. We found these cellular factors 
      were essential for endosomal protein trafficking and formation of the VS and that 
      depletion of target proteins prevented virus trafficking to the plasma membrane 
      by retaining virus in intracellular vesicles. Identification of key regulators in 
      HIV-1 trans-infection between DC and CD4(+) T cells has the potential for the 
      development of targeted therapy to reduce trans-infection of HIV-1 in vivo.
CI  - Copyright (c) 2020 Bayliss et al.
FAU - Bayliss, Rebecca
AU  - Bayliss R
AUID- ORCID: 0000-0002-3324-957X
AD  - Division of Infection and Immunity, School of Medicine, Cardiff University, 
      Cardiff, United Kingdom.
FAU - Wheeldon, James
AU  - Wheeldon J
AD  - Division of Infection and Immunity, School of Medicine, Cardiff University, 
      Cardiff, United Kingdom.
FAU - Caucheteux, Stephan M
AU  - Caucheteux SM
AD  - Department of Medicine, University of Toronto, Toronto, Canada.
FAU - Niessen, Carien M
AU  - Niessen CM
AD  - Department of Dermatology, Cologne Excellence Cluster on Cellular Stress 
      Responses in Aging Associated Diseases (CECAD), and Center for Molecular 
      Medicine, University of Cologne, Cologne, Germany.
FAU - Piguet, Vincent
AU  - Piguet V
AD  - Division of Infection and Immunity, School of Medicine, Cardiff University, 
      Cardiff, United Kingdom vincent.piguet@utoronto.ca.
AD  - Division of Dermatology, Women's College Hospital, Toronto, Canada.
AD  - Division of Dermatology, Department of Medicine, University of Toronto, Toronto, 
      Canada.
LA  - eng
GR  - WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200416
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (BIN1 protein, human)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Rab29 protein, human)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 0 (gag Gene Products, Human Immunodeficiency Virus)
RN  - EC 3.6.1.-. (RAB8A protein, human)
RN  - EC 3.6.5.2 (ADP-Ribosylation Factor 1)
RN  - EC 3.6.5.2 (rab GTP-Binding Proteins)
SB  - IM
MH  - ADP-Ribosylation Factor 1/metabolism
MH  - Adaptor Proteins, Signal Transducing/metabolism
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - Dendritic Cells/*immunology/virology
MH  - HIV Infections/*genetics/virology
MH  - HIV-1/*immunology/pathogenicity
MH  - High-Throughput Screening Assays/methods
MH  - Humans
MH  - Immunological Synapses/*metabolism
MH  - Monocytes/metabolism
MH  - Nuclear Proteins/metabolism
MH  - Primary Cell Culture
MH  - Protein Transport/genetics
MH  - Tumor Suppressor Proteins/metabolism
MH  - Virion/metabolism
MH  - Virus Replication
MH  - gag Gene Products, Human Immunodeficiency Virus/metabolism
MH  - rab GTP-Binding Proteins/metabolism
PMC - PMC7163131
OTO - NOTNLM
OT  - HIV-1
OT  - T-cell immunity
OT  - dendritic cell
OT  - host-cell interactions
OT  - virological synapse
EDAT- 2020/02/23 06:00
MHDA- 2020/10/21 06:00
PMCR- 2020/04/16
CRDT- 2020/02/21 06:00
PHST- 2019/09/18 00:00 [received]
PHST- 2020/02/04 00:00 [accepted]
PHST- 2020/02/23 06:00 [pubmed]
PHST- 2020/10/21 06:00 [medline]
PHST- 2020/02/21 06:00 [entrez]
PHST- 2020/04/16 00:00 [pmc-release]
AID - JVI.01597-19 [pii]
AID - 01597-19 [pii]
AID - 10.1128/JVI.01597-19 [doi]
PST - epublish
SO  - J Virol. 2020 Apr 16;94(9):e01597-19. doi: 10.1128/JVI.01597-19. Print 2020 Apr 
      16.