Effects of the immunomodulating agent R837 on acute and latent herpes simplex virus type 2 infections.
R837 is an immune modulator with no in vitro activity against herpes simplex virus (HSV). We evaluated topical R837 as therapy for genital HSV type 2 infection using the guinea pig model of this disease. Furthermore, we investigated the effect of R837 therapy on acute and latent neural HSV infections. Therapy initiated 12 h after viral inoculation and given twice a day significantly reduced the acute neural infection so that HSV was recovered from only 1 of 64 neural tissue specimens obtained from R837 recipients compared with 43 of 56 specimens obtained from placebo recipients (P less than 0.0001). R837 initiated 36 h after HSV inoculation and given once a day also significantly reduced the total mean lesion score of the acute disease from 14.1 +/- 4.3 to 2.6 +/- 5.3 (P less than 0.0001) and shortened the period of vaginal HSV shedding from 6.9 +/- 1.7 to 3.2 +/- 1.4 days (P less than 0.001). R837-treated animals also developed fewer HSV recurrences than did controls (2.0 +/- 1.7 versus 5.1 +/- 1.7; P less than 0.0002). Latent HSV was detected in 23 of 24 dorsal root ganglia explant cultures from placebo recipients but in only 2 of 30 cultures from R837-treated animals, and HSV in these 2 cultures was detectable only with the addition of a demethylating agent. Topical R837 exhibited in vivo anti-HSV activity, reducing both acute and latent neural infections as well as acute and recurrent genital disease.
Bernstein
D I
DI
Division of Infectious Diseases, Children's Hospital Research Foundation, Cincinnati, Ohio 45229.
Harrison
C J
CJ
D000276:Adjuvants, Immunologic / Q000009:adverse effects / Q000627:therapeutic use*; D000634:Aminoquinolines; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006168:Guinea Pigs; D006561:Herpes Simplex / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D000077271:Imiquimod; D007372:Interferons / Q000032:analysis; D009422:Nervous System Diseases / Q000188:drug therapy / Q000382:microbiology; D011817:Rabbits; D012008:Recurrence; D013997:Time Factors
D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D007372:Interferons; D000077271:Imiquimod