A herpesvirus encoded deubiquitinase is a novel neuroinvasive determinant.
The neuroinvasive property of several alpha-herpesviruses underlies an uncommon infectious process that includes the establishment of life-long latent infections in sensory neurons of the peripheral nervous system. Several herpesvirus proteins are required for replication and dissemination within the nervous system, indicating that exploiting the nervous system as a niche for productive infection requires a specialized set of functions encoded by the virus. Whether initial entry into the nervous system from peripheral tissues also requires specialized viral functions is not known. Here we show that a conserved deubiquitinase domain embedded within a pseudorabies virus structural protein, pUL36, is essential for initial neural invasion, but is subsequently dispensable for transmission within and between neurons of the mammalian nervous system. These findings indicate that the deubiquitinase contributes to neurovirulence by participating in a previously unrecognized initial step in neuroinvasion.
Lee
Joy I
JI
Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Sollars
Patricia J
PJ
Baver
Scott B
SB
Pickard
Gary E
GE
Leelawong
Mindy
M
Smith
Gregory A
GA
D000818:Animals; D000867:Anterior Chamber / Q000821:virology; D001370:Axonal Transport / Q000502:physiology; D002522:Chlorocebus aethiops; D010450:Endopeptidases / Q000235:genetics / Q000502:physiology*; D015828:Eye Infections, Viral / Q000821:virology; D011558:Herpesvirus 1, Suid / Q000201:enzymology* / Q000235:genetics; D008297:Male; D011557:Pseudorabies / Q000503:physiopathology / Q000821:virology*; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000821:virology*; D025801:Ubiquitin / Q000378:metabolism*; D064570:Ubiquitin-Specific Proteases; D014709:Vero Cells; D015678:Viral Structural Proteins / Q000235:genetics / Q000502:physiology*
D025801:Ubiquitin; D015678:Viral Structural Proteins; D010450:Endopeptidases; D064570:Ubiquitin-Specific Proteases