Characterization of pseudorabies virus mutants expressing carboxy-terminal truncations of gE: evidence for envelope incorporation, virulence, and neurotropism domains.
Glycoprotein E (gE) gene of pseudorabies virus (PRV) is conserved among diverse alphaherpesviruses and therefore is predicted to be important for virus survival. gE contributes to viral spread from cell to cell in a variety of hosts and is responsible, in part, for increased virulence or pathogenesis of the virus. Virulence and spread mediated by gE are thought to be highly correlated. We initiated this study to explore the hypothesis that these two phenotypes might reflect separate functions of the gE protein. We did so by focusing on the role of the gE carboxy terminus in neuronal spread. Viruses harboring nonsense mutations affecting the expression of the gE cytoplasmic domain had several notable phenotypes. First, the truncated gE proteins expressed from these mutants are not found in virion envelopes. Second, the mutants retain the ability to spread to all retinorecipient regions of the rodent brain after retinal infection of rats. Third, the mutants have the reduced virulence phenotype of a gE deletion mutant in rats. Finally, the mutants have distinct plaque-size phenotypes on MDBK cells but not PK15 cells. Based on these observations, we suggest that gE-mediated virulence and spread may reflect separate functions that are not mediated by gE on virus particles.
Tirabassi
R S
RS
Department of Molecular Biology, Princeton University, New Jersey 08544, USA.
Townley
R A
RA
Eldridge
M G
MG
Enquist
L W
LW
D000818:Animals; D002417:Cattle; D002460:Cell Line; D004195:Disease Models, Animal; D016521:Electrophoresis, Gel, Pulsed-Field; D005123:Eye / Q000821:virology; D011558:Herpesvirus 1, Suid / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D008297:Male; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000821:virology; D011499:Protein Processing, Post-Translational; D011557:Pseudorabies / Q000821:virology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017384:Sequence Deletion; D013552:Swine; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010948:Viral Plaque Assay; D014771:Virion; D014774:Virulence / Q000235:genetics
D014759:Viral Envelope Proteins; C089580:glycoprotein E, Suid herpesvirus 1; C042966:pseudorabies virus glycoproteins