PMID- 33962010
OWN - NLM
STAT- MEDLINE
DCOM- 20220120
LR  - 20220716
IS  - 1095-953X (Electronic)
IS  - 0969-9961 (Print)
IS  - 0969-9961 (Linking)
VI  - 155
DP  - 2021 Jul
TI  - Extracellular vesicles regulate gap junction-mediated intercellular communication 
      and HIV-1 infection of human neural progenitor cells.
PG  - 105388
LID - S0969-9961(21)00137-6 [pii]
LID - 10.1016/j.nbd.2021.105388 [doi]
AB  - Human immunodeficiency virus-1 (HIV-1) has been shown to cross the blood-brain 
      barrier and cause HIV-associated neurocognitive disorders (HAND) through a 
      process that may involve direct or indirect interactions with the central nervous 
      system (CNS) cells and alterations of amyloid beta (Abeta) homeostasis. The present 
      study focused on the mechanisms of HIV-1 infecting human neural progenitor cells 
      (hNPCs) and affecting NPC intercellular communications with human brain 
      endothelial cells (HBMEC). Despite the lack of the CD4 receptor, hNPCs were 
      effectively infected by HIV-1 via a mechanism involving the chemokine receptors, 
      CXCR4 and CCR5. HIV-1 infection increased expression of connexin-43 (Cx43), 
      phosphorylated Cx43 (pCx43), and pannexin 2 (Panx2) protein levels in hNPCs, 
      suggesting alterations in gap-junction (GJ) and pannexin channel communication. 
      Indeed, a functional GJ assay indicated an increase in communication between 
      HIV-infected hNPCs and non-infected HBMEC. We next analyzed the impact of 
      HBMEC-derived extracellular vesicles (EVs) and EVs carrying Abeta (EV-Abeta) on the 
      expression of Cx43, pCx43, and Panx2 in HIV-1 infected and non-infected hNPCs. 
      Exposure to EV-Abeta resulted in significant reduction of Cx43 and pCx43 protein 
      expression in non-infected hNPCs when compared to EV controls. Interestingly, 
      EV-Abeta treatment significantly increased levels of Cx43, pCx43, and Panx2 in 
      HIV-1-infected hNPCs when compared to non-infected controls. These results were 
      confirmed in a GJ functional assay and an ATP release assay, which is an 
      indicator of connexin hemichannel and/or pannexin channel functions. Overall, the 
      current study demonstrates the importance of hNPCs in HIV-1 infection and 
      indicates that intercellular communications between infected hNPCs and HBMEC can 
      be effectively modulated by EVs carrying Abeta as their cargo.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Cho, Hyung Joon
AU  - Cho HJ
AD  - Department of Biochemistry and Molecular Biology, University of Miami Miller 
      School of Medicine, Miami, FL, 33136, USA. Electronic address: hjcho@arizona.edu.
FAU - Velichkovska, Martina
AU  - Velichkovska M
AD  - Department of Biochemistry and Molecular Biology, University of Miami Miller 
      School of Medicine, Miami, FL, 33136, USA.
FAU - Schurhoff, Nicolette
AU  - Schurhoff N
AD  - Department of Biochemistry and Molecular Biology, University of Miami Miller 
      School of Medicine, Miami, FL, 33136, USA.
FAU - Andras, Ibolya E
AU  - Andras IE
AD  - Department of Biochemistry and Molecular Biology, University of Miami Miller 
      School of Medicine, Miami, FL, 33136, USA.
FAU - Toborek, Michal
AU  - Toborek M
AD  - Department of Biochemistry and Molecular Biology, University of Miami Miller 
      School of Medicine, Miami, FL, 33136, USA. Electronic address: 
      mtoborek@med.miami.edu.
LA  - eng
GR  - R01 MH128022/MH/NIMH NIH HHS/United States
GR  - R01 DA044579/DA/NIDA NIH HHS/United States
GR  - R01 HL126559/HL/NHLBI NIH HHS/United States
GR  - R01 DA039576/DA/NIDA NIH HHS/United States
GR  - R01 DA050528/DA/NIDA NIH HHS/United States
GR  - R01 DA040537/DA/NIDA NIH HHS/United States
GR  - R21 MH122235/MH/NIMH NIH HHS/United States
GR  - R01 DA047157/DA/NIDA NIH HHS/United States
GR  - R01 MH072567/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20210505
PL  - United States
TA  - Neurobiol Dis
JT  - Neurobiology of disease
JID - 9500169
RN  - 0 (Amyloid beta-Peptides)
SB  - IM
MH  - Amyloid beta-Peptides/metabolism
MH  - Cell Communication/*physiology
MH  - Cell Line
MH  - Cells, Cultured
MH  - Endothelium, Vascular/metabolism/virology
MH  - Extracellular Vesicles/*metabolism/virology
MH  - Gap Junctions/*metabolism/virology
MH  - HIV Infections/*metabolism
MH  - HIV-1/*metabolism
MH  - Humans
MH  - Neural Stem Cells/*metabolism/virology
PMC - PMC9056881
MID - NIHMS1703477
OTO - NOTNLM
OT  - Amyloid beta
OT  - Connexins
OT  - Extracellular vesicles
OT  - HIV-1
OT  - Human neural progenitor cells
OT  - Pannexins
COIS- Declaration of Competing Interest The authors declare no conflict of interest.
EDAT- 2021/05/08 06:00
MHDA- 2022/01/21 06:00
PMCR- 2022/07/01
CRDT- 2021/05/07 20:22
PHST- 2021/02/15 00:00 [received]
PHST- 2021/04/13 00:00 [revised]
PHST- 2021/05/03 00:00 [accepted]
PHST- 2021/05/08 06:00 [pubmed]
PHST- 2022/01/21 06:00 [medline]
PHST- 2021/05/07 20:22 [entrez]
PHST- 2022/07/01 00:00 [pmc-release]
AID - S0969-9961(21)00137-6 [pii]
AID - 10.1016/j.nbd.2021.105388 [doi]
PST - ppublish
SO  - Neurobiol Dis. 2021 Jul;155:105388. doi: 10.1016/j.nbd.2021.105388. Epub 2021 May 
      5.