Dephosphorylation of eIF2alpha mediated by the gamma134.5 protein of herpes simplex virus 1 facilitates viral neuroinvasion.
The gamma(1)34.5 protein, a virulence factor of herpes simplex viruses, redirects protein phosphatase 1 to dephosphorylate the alpha subunit of translation initiation factor 2 (eIF2alpha). Additionally, it inhibits the induction of antiviral genes by TANK-binding kinase 1. Nevertheless, its precise role in vivo remains to be established. Here we show that eIF2alpha dephosphorylation by gamma(1)34.5 is crucial for viral neuroinvasion. V(193)E and F(195)L substitutions in gamma(1)34.5 abrogate viral replication in the eye and spread to the trigeminal ganglia and brain. Intriguingly, inhibition of antiviral gene induction by gamma(1)34.5 is not sufficient to exhibit viral virulence.
Verpooten
Dustin
D
Department of Microbiology and Immunology, College of Medicine, University of Illinois, Chicago, Illinois 60612, USA.
Feng
Zongdi
Z
Valyi-Nagy
Tibor
T
Ma
Yijie
Y
Jin
Huali
H
Yan
Zhipeng
Z
Zhang
Cuizhu
C
Cao
Youjia
Y
He
Bin
B
D019943:Amino Acid Substitution; D000818:Animals; D001921:Brain / Q000821:virology; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism*; D005123:Eye / Q000821:virology; D018259:Herpesvirus 1, Human / Q000472:pathogenicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D012668:Trigeminal Ganglion / Q000821:virology; D014764:Viral Proteins / Q000235:genetics / Q000502:physiology*; D037521:Virulence Factors / Q000235:genetics / Q000502:physiology*
D015852:Eukaryotic Initiation Factor-2; D014764:Viral Proteins; D037521:Virulence Factors; C066469:gamma 34.5 protein, Human herpesvirus 1