Targeted delivery of DNA encoding herpes simplex virus type-1 glycoprotein D enhances the cellular response to primary viral challenge.
Intravenous injection of plasmid DNA encoding herpes simplex virus type-1 glycoprotein D (gD-1) complexed with asialoorosomucoid-poly-L-lysine (gD-ASOR) targets foreign DNA to the liver, leading to hepatic expression of gD-1. BALB/c mice were given two intravenous injections of gD-ASOR, pBK-ASOR (plasmid lacking the gD-1 gene but complexed with ASOR), or PBS. The skin was inoculated with 1 x 10(4) PFU of HSV-1 or sham-inoculated, and analyzed for infectious virus and cellular infiltration 1, 3, and 5 days after inoculation. Prior immunization with gD-ASOR led to significantly lower (P < 0.05) viral titers in the skin 5 days after inoculation compared with controls. Infiltration of the skin at the site of inoculation by polymorphonuclear neutrophils (PMNs), T cells, B cells, dendritic cells, and macrophages was monitored immunohistochemically. Significantly higher numbers (P < 0.05) of CD4+ and CD8+ T cells, dendritic cells, and macrophages responded to HSV-1 challenge in mice immunized with gD-ASOR than in mice immunized with pBK-ASOR or PBS. The response by PMNs and B cells was indistinguishable among the treatment groups. These results suggest that BALB/c mice sensitized to gD-1 following gD-ASOR immunization develop an enhanced T-cell response to primary HSV-1 infection.
Rogers
J V
JV
Biomedical Sciences Ph.D. Program, Wright State University, Dayton, Ohio 45435, USA.
Bigley
N J
NJ
Chiou
H C
HC
Hull
B E
BE
D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis; D001212:Asialoglycoproteins / Q000008:administration & dosage / Q000737:chemistry; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D019743:Chemokines, CXC / Q000032:analysis; D004279:DNA, Viral / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005260:Female; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007111:Immunity, Cellular / Q000276:immunology; D007150:Immunohistochemistry; D017493:Leukocyte Common Antigens / Q000032:analysis; D008565:Membrane Proteins / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D009961:Orosomucoid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry; D010957:Plasmids / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics; D011107:Polylysine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D009418:S100 Proteins / Q000032:analysis; D012867:Skin / Q000737:chemistry / Q000276:immunology; D013997:Time Factors; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*; D014777:Virus Diseases / Q000276:immunology / Q000517:prevention & control* / Q000821:virology
D000943:Antigens, Differentiation; D001212:Asialoglycoproteins; D015704:CD4 Antigens; D016827:CD8 Antigens; C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D019743:Chemokines, CXC; C515539:Cx3cl1 protein, mouse; D004279:DNA, Viral; D004337:Drug Carriers; D000949:Histocompatibility Antigens Class II; D008565:Membrane Proteins; D009961:Orosomucoid; D009418:S100 Proteins; D014759:Viral Envelope Proteins; C057326:asialoorosomucoid-polylysine conjugate; C039447:glycoprotein D, Human herpesvirus 1; C036763:monocyte-macrophage differentiation antigen; D011107:Polylysine; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1