Recurrent Herpetic Infection Research Articles

Cell-mediated immunity to herpes simplex virus in man.

The immune response to herpes simplex virus was assessed by complement fixation tests, in vitro stimulation of lymphocytes, and intradermal skin tests on 63 healthy volunteers and 26 patients receiving antilymphocyte globulin (ALG) and/or adrenocorticotropic hormone. Lymphocytes from subjects with frequent recurrent herpes infections all showed significant stimulation by herpes simplex antigen, but only four of 37 without a history of previous herpes were positive. Skin tests with herpes simplex antigen demonstrated intact delayed hypersensitivity in the 10 patients tested. Lymphocyte responses to phytohemagglutinin (PHA), purified protein derivative (PPD), streptokinase, or vaccinia were similar in subjects with or without previous herpes. We were, therefore, unable to demonstrate any defect in these parameters of the immune response in patients with recurrent herpes simplex infections. Therapy with ALG totally abrogated both in vitro and in vivo evidence of cell-mediated immunity and was associated with herpes labialis in seven of the 21 courses. These infections were more severe than usual, and it may be that the cell-mediated response is more important in the localization of recurrent herpetic infections than in their prevention.

Cell-mediated immunity to herpes simplex virus in man.

The immune response to herpes simplex virus was assessed by complement fixation tests, in vitro stimulation of lymphocytes, and intradermal skin tests on 63 healthy volunteers and 26 patients receiving antilymphocyte globulin (ALG) and/or adrenocorticotropic hormone. Lymphocytes from subjects with frequent recurrent herpes infections all showed significant stimulation by herpes simplex antigen, but only four of 37 without a history of previous herpes were positive. Skin tests with herpes simplex antigen demonstrated intact delayed hypersensitivity in the 10 patients tested. Lymphocyte responses to phytohemagglutinin (PHA), purified protein derivative (PPD), streptokinase, or vaccinia were similar in subjects with or without previous herpes. We were, therefore, unable to demonstrate any defect in these parameters of the immune response in patients with recurrent herpes simplex infections. Therapy with ALG totally abrogated both in vitro and in vivo evidence of cell-mediated immunity and was associated with herpes labialis in seven of the 21 courses. These infections were more severe than usual, and it may be that the cell-mediated response is more important in the localization of recurrent herpetic infections than in their prevention.

Cell-mediated immunity in Herpesvirus hominis infections.

The cell-mediated and antibody responses to Herpesvirus hominis type 1 were investigated in patients with primary and recurrent herpetic infections. Stimulation of lymphocyte transformation with the virus and the complement fixing antibody titre did not differ significantly between patients and controls. However, macrophage migration inhibition and lymphocyte cytotoxicity were impaired in patients. The defects were specific to H. hominis, as Candida oblicans, which was used as an unrelated antigen, failed to show a similar abnormality. These results and preliminary sequential studies suggest that the susceptibility to recurrent herpesvirus infection may be due to an impaired production of macrophage migration inhibition factor and lymphocyte cytotoxicity in the presence of intact lymphocyte sensitization and antibody formation.

Latent herpes simplex virus from trigeminal ganglia of rabbits with recurrent eye infection.

LATENTLY infected sensory ganglia have been thought to be the source of virus for various clinical manifestations of recurrent herpetic disease in man1,2. In direct support of this concept, we recently showed that herpes simplex virus can induce a latent infection in the spinal ganglia of mice3. This murine infection has not, however, been shown to be accompanied by recurrent disease. Recurrent herpetic eye infection can be produced in the rabbit4. If sensory ganglia are involved in recurrent disease, then trigeminal ganglia from rabbits undergoing such recurrent infection would be expected to harbour latent virus. We now report that herpes simplex virus does indeed induce latent infection in trigeminal ganglia of rabbits presenting recurrent eye infection. As in the experiments with mice, infectious virus could not be recovered directly; it was only found when ganglia were established as organ cultures in vitro.

A Possible Role of γA-Immunoglobulin in Herpes Simplex Virus Infection in Man

Summary The capacities to synthesize γA in normal subjects and persons with primary and recurrent herpetic infections were analyzed and compared. Complications of primary infections and recurrences appeared to be associated with a deficiency of herpes-specific γA. The threshold protective titer of this γA appeared to be 12 to 20. The initial immune response to herpes infection was characterized by a marked increase in the γM titer, followed after 21 days by a predominance of γA and γG. The protective effect of γA in the mucocutaneous tissues appears to be associated with its high avidity for the herpes simplex virus and its active secretion by such tissues.

Anaemias of marasmus and kwashiorkor in Kenya.

<h3>Discussion and Summary</h3> The colorimetric neutralization test for herpes simplex described in this report is considerably easier to conduct than neutralization tests in mice or embryonated eggs, and lends itself to large-scale studies. Also, the constant virusvarying serum technique, widely regarded as more sensitive than the constant serum-varying virus method for detecting differences in levels of neutralizing antibody, is utilized. As a tool for epidemiologic and diagnostic purposes, the neutralization test was found comparable to the complement fixation test in its ability to demonstrate 4-fold or greater titer rises. It would appear that either the complement fixation or colorimetric neutralization test would be adequate for diagnosis of primary herpetic infections, and that little would be gained diagnostically by the use of both tests except in instances where equivocal results were obtained with one test. Only 2 of 31 4-fold or greater rises in antibody titer were detected by the neutralization test, but not the complement fixation test, and only 3 of the 31 antibody rises were detected by the complement fixation test, but not the neutralization test. Although the neutralizing antibody titers tended to be somewhat higher than the complement-fixing antibody titers, they both increased at approximately the same rate in cases of primary herpetic infections. This is in contrast to the antibody response in many other viral diseases in which neutralizing antibodies appear long before complement-fixing antibodies, and may even reach their maximal titer by the time of onset of the illness, <i>e.g.</i>, poliomyelitis (19). The neutralizing antibody titers detected by the colorimetric method showed good correlation with the complement-fixing antibody titers for the same sera (<i>r</i> = 0.82). This correlation between complement-fixing and neutralizing antibody titers was noted for individuals in all age groups studied, and it would appear, on the basis of the limited amount of data available, that production of both types of antibody is stimulated by recurrent herpetic infections, or that complement-fixing antibody persists for as long after primary infections as does neutralizing antibody.

A Colorimetric Neutralization Test for Herpes Simplex, with Observations on Neutralizing and Complement-Fixing Antibody Levels in Human Sera

Discussion and Summary The colorimetric neutralization test for herpes simplex described in this report is considerably easier to conduct than neutralization tests in mice or embryonated eggs, and lends itself to large-scale studies. Also, the constant virusvarying serum technique, widely regarded as more sensitive than the constant serum-varying virus method for detecting differences in levels of neutralizing antibody, is utilized. As a tool for epidemiologic and diagnostic purposes, the neutralization test was found comparable to the complement fixation test in its ability to demonstrate 4-fold or greater titer rises. It would appear that either the complement fixation or colorimetric neutralization test would be adequate for diagnosis of primary herpetic infections, and that little would be gained diagnostically by the use of both tests except in instances where equivocal results were obtained with one test. Only 2 of 31 4-fold or greater rises in antibody titer were detected by the neutralization test, but not the complement fixation test, and only 3 of the 31 antibody rises were detected by the complement fixation test, but not the neutralization test. Although the neutralizing antibody titers tended to be somewhat higher than the complement-fixing antibody titers, they both increased at approximately the same rate in cases of primary herpetic infections. This is in contrast to the antibody response in many other viral diseases in which neutralizing antibodies appear long before complement-fixing antibodies, and may even reach their maximal titer by the time of onset of the illness, e.g., poliomyelitis (19). The neutralizing antibody titers detected by the colorimetric method showed good correlation with the complement-fixing antibody titers for the same sera (r = 0.82). This correlation between complement-fixing and neutralizing antibody titers was noted for individuals in all age groups studied, and it would appear, on the basis of the limited amount of data available, that production of both types of antibody is stimulated by recurrent herpetic infections, or that complement-fixing antibody persists for as long after primary infections as does neutralizing antibody.

The Effect of the Temperature of Incubation on the Spread of Herpes Simplex Virus in an Immune Environment in Cell Culture

Summary The MP variant of Herpes simplex virus was used in experiments designed to determine the relative rates of spread of virus infection from infected to noninfected FL cells incubated at different temperatures in the presence of antibody. Preliminary experiments showed that one infectious particle is sufficient to infect a cell, and that an infected cell will almost invariably produce a macroplaque when deposited on a monolayer culture and incubated at 37°C in the presence of antibody. The conditions required to effect infection of all or most cells in an FL cell culture were also determined. On the basis of these experiments, the mean size of macroplaques formed by infected cells added to the monolayer culture and incubated in the presence of antibody at 30°, 31°, 34°, 37°, and 39.5°C were determined. From these experiments it was learned that the largest macroplaque area is attained after 4 days of incubation at 37°C. Below and above 37°C the mean size of macroplaques after a similar incubation period is progressively reduced. In view of the absence of the cell fluid-cell transmission of infection in the presence of antibody in the fluid phase, the increase in macroplaques may be taken as a measure of the direct cell-cell transmission of the virus from infected to noninfected cells. The significance of the observed rates of spread of infection at different temperatures with respect to a) virus formation at different temperatures, b) virus release from infected cells at different temperatures, and c) recurrent herpetic infections in man were discussed.

Studies on herpes simplex virus. III. The effects of roentgen radiation, cortisone and gastric mucin upon the infectivity of herpes simplex virus for laboratory mice.

It has seemed reasonable to assume that the pathogenesis of recurrent herpetic infection is determined by an alteration in host resistance. The immunological investigation reported previously1 provided no evidence that fluctuations in the titer of autogenous virus or of the antibody circulating in its host influenced the course of infection. Hence, it was of interest to inquire whether herpes simplex virus infection was susceptible to the action of agents capable of altering the natural resistance of the host.