Herpes simplex virus type 1 glycoprotein E domains involved in virus spread and disease.
Herpes simplex virus type 1 (HSV-1) glycoprotein E (gE) functions as an immunoglobulin G (IgG) Fc binding protein and is involved in virus spread. Previously we studied a gE mutant virus that was impaired for IgG Fc binding but intact for spread and another that was normal for both activities. To further evaluate the role of gE in spread, two additional mutant viruses were constructed by introducing linker insertion mutations either outside the IgG Fc binding domain at gE position 210 or within the IgG Fc binding domain at position 380. Both mutant viruses were impaired for spread in epidermal cells in vitro; however, the 380 mutant virus was significantly more impaired and was as defective as gE null virus. gE mutant viruses were inoculated into the murine flank to measure epidermal disease at the inoculation site, travel of virus to dorsal root ganglia, and spread of virus from ganglia back to skin to produce zosteriform lesions. Disease at the inoculation and zosteriform sites was reduced for both mutant viruses, but more so for the 380 mutant virus. Moreover, the 380 mutant virus was highly impaired in its ability to reach the ganglia, as demonstrated by virus culture and real-time quantitative PCR. The results indicate that the domain surrounding amino acid 380 is important for both spread and IgG Fc binding and suggest that this domain is a potential target for antiviral therapy or vaccines.
Saldanha
C E
CE
Division of Infectious Diseases, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6073, USA.
Lubinski
J
J
Martin
C
C
Nagashunmugam
T
T
Wang
L
L
van Der Keyl
H
H
Tal-Singer
R
R
Friedman
H M
HM
D000818:Animals; D015139:Blotting, Southern; D015153:Blotting, Western; D002460:Cell Line; D002522:Chlorocebus aethiops; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D005727:Ganglia, Spinal / Q000821:virology; D006561:Herpes Simplex / Q000473:pathology / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000378:metabolism; D007074:Immunoglobulin G / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016254:Mutagenesis, Insertional; D017434:Protein Structure, Tertiary; D012367:RNA, Viral / Q000032:analysis; D012397:Rosette Formation; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism
D004279:DNA, Viral; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D012367:RNA, Viral; D014759:Viral Envelope Proteins; C044768:glycoprotein E, herpes simplex virus type 1