PMID- 38538289
OWN - NLM
STAT- MEDLINE
DCOM- 20240329
LR  - 20240409
IS  - 2768-6698 (Electronic)
IS  - 2768-6698 (Linking)
VI  - 29
IP  - 3
DP  - 2024 Mar 20
TI  - Host Cell-dependent Modulatory Role of Ras Homolog Enriched in Brain-Like-1 
      (RhebL1) Protein in Influenza A/NWS/33 Virus-infected Mammalian Cells.
PG  - 116
LID - 10.31083/j.fbl2903116 [doi]
AB  - BACKGROUND: The Mammalian Target of Rapamycin (mTOR) signaling pathway regulates 
      protein phosphorylation and exerts control over major cellular processes. mTOR is 
      activated by the small G-protein Ras Homolog Enriched in Brain (Rheb), which is 
      encoded by the Rheb1 and Rheb-like-1 (RhebL1) genes. There is currently a paucity 
      of information on the role of RhebL1, and specifically its involvement in viral 
      infection. In the present study we investigated the role of RhebL1 during human 
      influenza A/NWS/33 (NWS/33) (H1N1) virus infection of rhesus monkey-kidney 
      (LLC-MK2) cells and human type II alveolar epithelial (A549) cells. METHODS: To 
      assess the efficiency of NWS/33 virus replication, the expression of viral 
      nucleoprotein was examined by indirect immunofluorescence (IIF) and the viral 
      yield by fifty percent tissue culture infectious dose assay. An RNA-mediated RNA 
      interference approach was used to investigate the role of RhebL1 during NWS/33 
      infection. RhebL1 expression was evaluated by IIF, Western blotting, and 
      enzyme-linked immunosorbent assays. A two-tailed Student's t-test was applied to 
      evaluate differences between groups. RESULTS: RhebL1 was differentially expressed 
      in the cell models used in this study. Silencing of the RhebL1 gene led to 
      increased NWS/33 virus infection in A549 cells, but not in LLC-MK2 cells. 
      Moreover, the expression of hyperphosphorylated cytokeratin 8, a marker of NWS/33 
      virus infection efficiency, increased in A549 cells depleted of RhebL1 but 
      remained almost unchanged in LLC-MK2 cells. CONCLUSIONS: These are the first 
      results showing involvement of the endogenous RhebL1 protein during viral 
      infection. Our data suggests that RhebL1 exerts a host cell-dependent modulatory 
      role during influenza virus infection. RhebL1 appears to be a restrictive factor 
      against NWS/33 virus replication in A549 cells, but not in LLC-MK2.
CI  - (c) 2024 The Author(s). Published by IMR Press.
FAU - Buttrini, Mirko
AU  - Buttrini M
AD  - Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy.
FAU - De Conto, Flora
AU  - De Conto F
AD  - Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy.
LA  - eng
GR  - Italian Ministry of Education, University and Research (MIUR)/
PT  - Journal Article
PL  - Singapore
TA  - Front Biosci (Landmark Ed)
JT  - Frontiers in bioscience (Landmark edition)
JID - 101612996
RN  - 0 (Ras Homolog Enriched in Brain Protein)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Humans
MH  - Brain/metabolism
MH  - *Influenza A virus/physiology
MH  - *Influenza A Virus, H1N1 Subtype/metabolism
MH  - *Influenza, Human/genetics
MH  - Ras Homolog Enriched in Brain Protein/metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Macaca mulatta
MH  - Animals
OTO - NOTNLM
OT  - RhebL1 protein
OT  - influenza A virus
OT  - phosphorylated keratin 8
OT  - restriction factor
OT  - small interfering RNA
OT  - virus-host interaction
COIS- The authors declare no conflict of interest.
EDAT- 2024/03/28 00:45
MHDA- 2024/03/29 06:46
CRDT- 2024/03/27 22:23
PHST- 2023/10/24 00:00 [received]
PHST- 2024/02/23 00:00 [revised]
PHST- 2024/03/04 00:00 [accepted]
PHST- 2024/03/29 06:46 [medline]
PHST- 2024/03/28 00:45 [pubmed]
PHST- 2024/03/27 22:23 [entrez]
AID - S2768-6701(24)01252-8 [pii]
AID - 10.31083/j.fbl2903116 [doi]
PST - ppublish
SO  - Front Biosci (Landmark Ed). 2024 Mar 20;29(3):116. doi: 10.31083/j.fbl2903116.