Studies on Herpetic Infection in Mice

Abstract

In previously reported studies (1-3) it was found that in young mice the intranasal instillation of herpes virus (HF strain) was followed by the prompt invasion of the central nervous system (CNS) by way of all available neural routes. Death resulted regularly on the 4th or 5th day after inoculation, Specific antibodies, acquired as the result of an intraperitoneal injection of immune rabbit serum or by suckling an immune mother, protected young mice from herpetic infection of this sort. In these experiments the antibodies were present in the mice at the time the virus was administered. They presumably protected the mice by preventing the formation of peripheral foci of infection from which invasion of the CNS could occu~In order to determine whether passively acquired antibodies can significantly influence the course of herpetic infection within the CNS of mice, further investigations have been carried out. Disturbance of the "blood-brain barrier," which might affect the penetration of antibodies into the CNS, was avoided by the use of a peripheral site of inoculation. Specific antiserum was injected at various intervals after introduction of the virus, before involvement of the nervous system became apparent. When experimental herpetic infections induced in this manner are treated by administering specific antiserum prior to the appearance of obvious signs of involvement of the nervous system, it is virtually impossible to be certain whether an efficacious result is due to the effect of antibodies at the peripheral focus or within the nervous system. In experiments included in the present report, this difficulty has been circumvented by eliminating, by amputation, the peripheral focus as a complicating factor. It was found that hyperimmune rabbit serum,'injected intraperitoneally, can retard, and in some cases can completely arrest, the progress of an established herpetic infection within the nervous system of mice.

Pathogenesis of Herpes Simplex Virus in Congenitally Athymic Mice: the Relative Roles of Cell-mediated and Humoral Immunity

“…The nude mice infected s.c. in the pinna with 10 4 p.f.u, of HSV-1 (SC16) produced a local infection which spread sequentially along the peripheral nerves to the central nervous system. This type of progression has been observed previously in juvenile conventional mice after foot-pad and nasal mucosal infections (Evans et al, 1946;Slavin & Berry, 1943). It has also been observed in more mature conventional mice inoculated with larger doses of virus (Hill et al, 1975) and in mice previously given 10% NaC1 s.c. (Olitsky & Schlesinger, 1941;Wildy, 1967;Stevens & Cook, 1971).…”

“…In our model, the passive transfer of a polyclonal neutralizing antiserum resulted in a marked reduction of infectious virus in ganglia. Similar observations have been made on juvenile conventional mice (Evans et al, 1946). Our results differ from those of Openshaw et al (1979); in their study, transfer of immune anti-herpesvirus serum did not prevent the development of acute ganglionic infection in nude mice.…”

Determinants of Protection by Human Immune Globulin against Experimental Herpes Neonatorum

“…However, the reason for lack of protection may have been the low concentrations of antibodies in these passively administered sera. We and others have shown, for example, that hyperimmune antisera to HSV will protect newborn mice against a lethal dose of HSV given subcutaneously, intranasally , and intracerebrally (15,16,21,22). We now extend the studies in the mouse model to: (a) examine the dose variables which govern the effectiveness of neutralizing antibody during postexposure prophylaxis of experimental HSV infection, (b) determine the effectiveness of human antibodies in various potencies in protection against experimental herpes neonatorum, and (c) determine whether human antibodies are protective against different antigenic types and strains of HSV.…”

Alteration of Mortality and Pathogenesis of Three Experimental Herpesvirus hominis Infections of Mice with Adenine Arabinoside 5′-Monophosphate, Adenine Arabinoside, and Phosphonoacetic Acid

“…or i.p. herpes infections with passive antibody has reduced mortality (2,4,6,11,31). Therapy with ara-AMP and ara-A may be unable to alter H. hominis infections initiated by the intranasal or intravaginal route because virus is transmitted from infected mucous membranes directly to the CNS by peripheral nerves (current study; 18,24), and the two drugs do not reach sufficient concentration in the peripheral nervous system to interrupt transmission or inhibit viral replication.…”