Reciprocal regulation of AKT and MAP kinase dictates virus-host cell fusion.
Viruses of the Paramyxoviridae family bind to their host cells by using hemagglutinin-neuraminidase (HN), which enhances fusion protein (F)-mediated membrane fusion. Although respiratory syncytial virus and parainfluenza virus 5 of this family are suggested to trigger host cell signaling during infection, the virus-induced intracellular signals dictating virus-cell fusion await elucidation. Using an F- or HN-F-containing reconstituted envelope of Sendai virus, another paramyxovirus, we revealed the role and regulation of AKT1 and Raf/MEK/ERK cascades during viral fusion with liver cells. Our observation that extracellular signal-regulated kinase (ERK) activation promotes viral fusion via ezrin-mediated cytoskeletal rearrangements, whereas AKT1 attenuates fusion by promoting phosphorylation of F protein, indicates a counteractive regulation of viral fusion by reciprocal activation of AKT1 and mitogen-activated protein kinase (MAPK) cascades, establishing a novel conceptual framework for a therapeutic strategy.
Sharma
Nishi R
NR
Department of Biochemistry, University of Delhi South Campus, Benito Juarez Road, New Delhi 110021, India.
Mani
Prashant
P
Nandwani
Neha
N
Mishra
Rajakishore
R
Rana
Ajay
A
Sarkar
Debi P
DP
D002460:Cell Line; D015707:HN Protein / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D029082:Sendai virus / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D014760:Viral Fusion Proteins / Q000235:genetics / Q000378:metabolism; D053586:Virus Internalization
D015707:HN Protein; D014760:Viral Fusion Proteins; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D048052:Mitogen-Activated Protein Kinase 3