Disruption of the U(L)41 gene in the herpes simplex virus 2 dl5-29 mutant increases its immunogenicity and protective capacity in a murine model of genital herpes.
The herpes simplex virus 2 dl5-29 replication-defective mutant virus has been shown to induce protective immunity in mice and both prophylactic and therapeutic immunity in guinea pigs. In an attempt to improve the efficacy of dl5-29 we disrupted its U(L)41 gene, producing the triple mutant virus dl5-29-41L. dl5-29-41L has a decreased ability to inhibit host cell protein synthesis and a reduced cytopathic effect on cultured cells. When used to immunize mice, dl5-29-41L elicited significantly stronger neutralizing antibody responses and significantly stronger CD4(+) and CD8(+) cellular immune responses than dl5-29. The enhanced immune responses corresponded with increased protective capacity in a murine model of genital herpes. The protective immunity elicited by either virus was very durable, protecting mice for at least 7 months. Furthermore, we show that cell lysate preparations of both viruses were significantly more efficacious than the corresponding extracellular virus preparations.
Dudek
Timothy
T
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA.
Mathews
Lydia C
LC
Knipe
David M
DM
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D003673:Defective Viruses / Q000235:genetics* / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D017353:Gene Deletion; D006558:Herpes Genitalis / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D022301:Herpes Simplex Virus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009154:Mutation; D009500:Neutralization Tests; D014764:Viral Proteins / Q000235:genetics*
D000914:Antibodies, Viral; D022301:Herpes Simplex Virus Vaccines; D014764:Viral Proteins; C064566:herpes simplex virus type 2 protein UL41