Bohumir Dr. Lukas

Enhancement of host resistance against virus infections by MTP-PE, a synthetic lipophilic muramyl peptide--I. Increased survival in mice and guinea pigs after single drug administration prior to infection, and the effect of MTP-PE on interferon levels in sera and lungs.

Muramyl tripeptide-phosphatidylethanolamine (MTP-PE, CGP 19835) displays prophylactic antiviral activity in mice infected with influenza viruses A and B, parainfluenza 1 virus or herpes simplex type 1 viruses (HSV/1) and in guinea pigs infected with herpes simplex type 2 viruses (HSV/2). MTP-PE is effective when given in a single intranasal dose as early as 1-4 weeks before infection. In the case of HSV/2 infections, prophylactic effectiveness can be demonstrated after a single topical application into the vagina seven days before infection. Antiviral effects are observed in response to doses as little as 0.001 mg/kg bodyweight. The activity of the substance seems to be inversely related to the size of the viral inoculum, but poor dose-effect relation is demonstrable in a dose-range extending over four to five orders of magnitude. Furthermore, the compound is devoid of antiviral effects in vitro. MTP-PE does not induce interferon (IFN) in serum and lung, nor does it influence kinetics or quantity of serum and lung IFN content in the course of viral infections. However, when given intranasally 7 days before an oral dose of tilorone, increased levels of IFN in lung suspensions are observed.

Genital herpes in guinea-pigs. An experimental model with herpesvirus hominis.

The differentiation of herpesvirus hominis (HVH) into two serological types 1 and 2 (1), of which t tVH2 is predominantly found in genital herpes (2), the increasing incidence of genital herpes in man and certain evidence implicating HVH2 in carcinoma of the cervix (e.g. 3, 4, 5) have stimulated efforts to elaborate a suitable experimental model of genital herpes. Studies in mice have yielded no satisfactory results (6, 7). For some years, we have been endeavouring to develop a model of genital infection in other species of animal. NA~MIAS et. al. (8) have meanwhile reported on positive results in monkeys, which have been confirmed by other authors (9, 10, 11). The results we have obtained so far are summed up below: In our initial experiments, male (preputium and penis) and female (intravaginal) guinea-pigs, adult rabbits and beagle-dogs, oestradiol-progestercne primed juvenile female rabbits, rats and mice, were inoculated with HVH2/Angelotti 1, grown in HeLa cell culture. None of the male animals showed any symptoms of genital infection. In female beagles and adult rabbits, slight transient local symptoms were observed. In mice only encephalitis developed in about 30 per cent of the animals. Clearly positive symptoms were found in female guinea-pigs. In these, strain differences were seen between albino (Pirbright) and eoloured animals in that albinos proved more sensitive to the infection (see Table). The method of infection adopted in female guinea-pigs (i50--200 g body weight) was developed as a model for genital herpes. After slight abrasion of the vaginal mucosa, a small piece of fibrin foam (SEvAc, Prague), measuring 10 • 5 • 4 ram, was introduced into the vagina. The foam was impregnated with various PFU of

Herpes genitalis in guinea-pigs. I. Kinetic study in infection with Herpesvirus hominis type 2.

SummaryThe kinetics of virus replication after vaginal infection of guinea-pigs with HVH 2/Angelotti were studied in relation to the appearance of local and general symptoms. Most virus was isolated from the genital tract 24–48 hours post infection. Virus was first isolated from the spinal cord 48–72 hours post infection. Penetration into the brain only occurred occasionally, and later. Under the experimental conditions employed, no virus was found in the blood, spleen, kidneys, adrenals or inguinal lymph nodes. The local symptoms (typical genital herpes) and the general symptoms (paralysis and death) started after maximum virus replication had been reached and seemed to be a consequence of neural, rather than of haematogenic or lymphogenic spread.

Herpes genitalis in guinea-pigs. II. Morphological studies in female guinea-pigs infected with Herpesvirus hominis type 2.

SummaryGross and microscopial morphological changes developing in female guinea-pigs after vaginal infection with HVH 2/Angelotti were studied. In the mucosa of the external genital tract there were inflammatory changes with formation of intra-epithelial vesicles, erosions and ulcerations. In the late stages of the infection signs of inflammatory dysplasia were also observed. The infection spread into the nervous system and produced characteristic inflammatory changes. The inflammation began as a bilateral posterior myelitis and ascended in the course of infection through the upper spinal-cord towards the brain-stem. The morphological changes were preceded by increased virus replication in the respective tissues and were correlated in time with clinical symptoms. The morphological changes seen at the site of inoculation in the external genital tract of the guinea-pig bore a certain resemblance to those seen in some cases of human infection with the same type of virus.