Acyclovir Treatment of Skin Lesions Results in Immune Deviation in Mice Infected Cutaneously with Herpes Simplex Virus

Abstract

Clinical observations indicate that the antibody response to herpes simplex virus (HSV) in patients undergoing acyclovir treatment is reduced and, although the exact mechanism is not clear, some authors interpret it as immunosuppression. In order to clarify the mechanism, we cutaneously infected mice with HSV-1 and treated the resulting skin lesions with acyclovir. The immune response to infection and treatment in these mice was then analysed. Acyclovir treatment was given orally (20 mg/kg, three times daily), starting on day 0 (D0), 2 (D2) or 4 (D4) after infection and continuing until day 10. The serum antibody titre and the severity of skin lesions were significantly higher in the shortest treatment group (D4) than in the longer treatment groups (D0 and D2). In contrast, a skin test analysing delayed-type hypersensitivity (DTH) to HSV antigen showed that the D0 and D2 groups exhibited stronger DTH than the D4 group. Acyclovir treatment failed to cause a dissociation between DTH and antibody production in mice immunized with inactivated HSV antigen. However, acyclovir treatment in infected mice suppressed the development of skin lesions and resulted in a dissociation between DTH response and antibody production, indicating a typical immune deviation. This was supported by a change in the ratio of the isotype antibody IgG2a to IgG1. The treatment of skin lesions with acyclovir reduced the level of antibody response, as observed clinically. This indicates that the reduced antibody response in patients treated with acyclovir may be, at least in part, due to immune deviation and not immunosuppression.

Persistence of Infectious Herpes Simplex Virus Type 2 in the Nervous System in Mice after Antiviral Chemotherapy

“…One hypothesis, therefore, to explain our data is that a toxic effect of VACV in the infected mice interfered with the immune response to infection during the acute phase and that this allowed a transient survival of infectious virus in the period after withdrawing therapy. Others have reported that ACV may have a subtle effect on the immune response to HSV antigens in mice when administered from early times during the acute phase of virus replication (16). Furthermore, it has been suggested that ACV treatment causes a smaller rise in antibody production than placebo treatment, and this has been interpreted as an immunosuppressive effect of ACV treatment (3,6,12).…”

Effect of immunity on gene delivery into anterior horn motor neurons by live attenuated herpes simplex virus vector

“…50 Briefly, ELISA plates were coated with HSV-1 (HF) antigen overnight at 4°C. The plates were washed with PBS and blocked with 3% skim milk in PBS.…”