Interleukin-12- and gamma interferon-dependent innate immunity are essential and sufficient for long-term survival of passively immunized mice infected with herpes simplex virus type 1.
Interferon (IFN) type I (alpha/beta IFN [IFN-alpha/beta]) is very important in directly controlling herpes simplex virus type I (HSV-1) replication as well as in guiding and upregulating specific immunity against this virus. By contrast, the roles of IFN type II (IFN-gamma) and antibodies in the defense against HSV-1 are not clear. Mice without a functional IFN system and no mature B and T cells (AGR mice) did not survive HSV-1 infection in the presence or absence of neutralizing antibodies to the virus. Mice without a functional IFN type I system and with no mature B and T cells (AR129 mice) were unable to control infection with as little as 10 PFU of HSV-1 strain F. By contrast, in the presence of passively administered neutralizing murine antibodies to HSV-1, some AR129 mice survived infection with up to 10(4) PFU of HSV-1. This acute immune response was dependent on the presence of interleukin-12 (IL-12) p75. Interestingly, some virus-infected mice stayed healthy for several months, at which time antibody to HSV-1 was no longer detectable. Treatment of these virus-exposed mice with dexamethasone led to death in approximately 40% of the mice. HSV-1 was found in brains of mice that did not survive dexamethasone treatment, whereas HSV-1 was absent in those that survived the treatment. We conclude that in the presence of passively administered HSV-1-specific antibodies, the IL-12-induced IFN-gamma-dependent innate immune response is able to control low doses of virus infection. Surprisingly, in a significant proportion of these mice, HSV-1 appears to persist in the absence of antibodies and specific immunity.
Vollstedt
S
S
Institute of Virology, University of Zurich, Zurich, Switzerland.
Franchini
M
M
Alber
G
G
Ackermann
M
M
Suter
M
M
D000818:Animals; D000914:Antibodies, Viral / Q000008:administration & dosage; D001921:Brain / Q000821:virology; D003907:Dexamethasone / Q000627:therapeutic use; D004195:Disease Models, Animal; D017353:Gene Deletion; D016654:Genes, RAG-1; D005938:Glucocorticoids / Q000627:therapeutic use; D006561:Herpes Simplex / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000276:immunology / Q000472:pathogenicity*; D007110:Immunity, Active; D007113:Immunity, Innate; D007116:Immunization, Passive; D007371:Interferon-gamma / Q000276:immunology*; D018664:Interleukin-12 / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009500:Neutralization Tests; D017471:Receptors, Interferon / Q000172:deficiency / Q000235:genetics; D014774:Virulence
D000914:Antibodies, Viral; D005938:Glucocorticoids; D017471:Receptors, Interferon; D018664:Interleukin-12; D003907:Dexamethasone; D007371:Interferon-gamma