Lars Kjellén

Dane Particles, DNA Polymerase, and e-Antigen in Two Different Categories of Hepatitis B Antigen Carriers

Two different categories of hepatitis B antigen carriers have been investigated. One comprises patients treated with dialysis and known to be highly infectious. The other consists of blood donors found in routine screenings. Serum specimens have been studied with regard to Dane particles. Dane-core-associated DNA polymerase activity, and e-antigen. The two groups differed markedly in the aspects studied. The five healthy blood donors had no, or very few, detectable Dane particles and no detectable DNA polymerase activity; four of the five healthy donors had antibodies against e-antigen. The one xickk donor and all six dialysis patients had many Dane particles and polymerase activity; five of the sick dialysis patients had e-antigen. Thus, these results further underline the difference between the two groups, and e-antigen and DNA polymerase activity could represent possible useful parameters for judging infectivity.

A study of adenovirus-host cell system by the plaque technique

Abstract A system has been described of producing HeLa and MAS cell monolayers on which adenoviruses types 4 and 5 produce well-defined plaques. The first visible plaques appear on the eighth day, and the number increases at a regular rate until after about 3 weeks they may reach ten times the original number. There is a linear relationship between virus input and number of plaques obtained. When adenovirus is put on these plates about half the virus attaches within the first 60 minutes. The first new virus appears at 18 hours, reaching a maximum in 36 hours with a yield of approximately 10 4 PFU per cell. All but a few per cent of the virus remains cell attached for as long as 72 hours. At high inputs (multiplicity 80), 90% of the cells become infective centers and the number of colony formers drops to 0.1%.

Effect of 5-halogenated pyrimidines on cell proliferation and adenovirus multiplication

Abstract Both 5-fluorodeoxyuridine (FUDR) and 5-bromodeoxyuridine (BUDR) exerted an inhibitory effect on the proliferation of the human cell strain MAS-A and on the multiplication of adenovirus type 5. The concentration of BUDR necessary to prevent cell proliferation was equal to that necessary to inhibit formation of infectious virus. FUDR blocked virus multiplication at a concentration approximately 100 times smaller than that required to prevent cell growth. FUDR protected the cells from cytopathic degeneration at the same time that it inhibited virus multiplication. No complement-fixing antigens could be detected under these conditions. BUDR, on the other hand, did not protect the cells from cytopathic effects. Full yields of complement-fixing antigens were obtained although the formation of infectious virus particles was blocked. Using FUDR as an inhibitor of DNA synthesis, it could be shown that adenovirus DNA synthesis preceded the formation of infectious virus particles by about 10 hours.

An Epidemic Among Swedish Children Caused by Adenovirus Type 3

An epidemic of “pharyngoconjunctival fever” which occurred in the middle of Sweden in the summer of 1955 is described. A correlation to infections with adenovirus type 3 was found.

Studies on an Unidentified Group of Cytopathic Agents.

Nine cytopathic agents are described which were isolated in tissue culture, four from the stools of cases with pharyngitis with tonsillitis and cervical lymphadenopathia, three from the stools and one from a mesenteric lymph node of three cases with mesenteric lymphadenitis and finally one from a paralytic case probably contemporaneously in fected with polio type 1. The agents gave the same cytopathic picture in tissue cultures as either the Sutherland strain ofNeva andEnders 4 or the RI-67 strain ofHilleman andWerner 5. Moreover, they had a CF antigen in common with these strains. By neutralization tests, however, the agents studied seemed to be separable into three different groups. Representative strains were found to be filterable and resistant to treatment with ethyl ether. The possible relations of the agents to the clinical symptoms encountered are briefly discussed.

On the occurrence of adenoviruses in Sweden.

I n the course of a study of some 800 stool specimens obtained in Stockholm during the epidemic of poliomyelitis in 1953 (21) five strains of adenoviruses were encountered. Similar agents were recovered from the stools of three patients with the diagnosis o€ mesenteric lymphadenitis. I n one of these cases the virus was also isolated from a mesenteric lymph node. The results of a detailed study of these first Swedish strains of adenoviruses have been reported previously (13). It was thus found that all strains shared complement fixing antigens with each other as well as with the agent RI-67 isolated by Hilleman & Werner (10) and with the Sutherland strain isolated by Neva & Enders (17). By neutralization tests on the other hand, the strains were separated into three groups. Other studies in the laboratory of Huebner (1 1) have established that these types of viruses can be classified together with agents isolated by them from various sources. The first report on such viruses thus seems to be that of Rowe and coworkers (19) on agents recovered from human adenoids. Various names for this virus group have been used by different authors, including APC (adenoidal-pharyngeal-conjunctival, (1 1) ), R I (respiratory illness, (10) ), and ARD (acute respiratory disease, ( 7 ) ) viruses. Recently the term Adenoviruses was agreed upon (5). Seventeen serologically distinct types of adenoviruses have so far been reported (18). By epidemiological, clinical and laboratory studies some types have, more or less definitely, been etiologically correlated to syndromes of human disease, such as various types of respiratory illnesses (10, 2, 7 , 3, 4) and kerato-conjunctivitis (12). The present paper is a report on the various strains of adenoviruses isolated in Sweden since 1953. Extensive data mll be given only in those cases where type 7 virus was isolated. The outbreaks of type 3 adenovirus

Studies on the interactions of adenovirus, antibody, and host cells in vitro

Abstract A study of the process of neutralization of adenovirus type 5 was performed using the plaque technique as an assay method. It was demonstrated that virus-antibody union is a rapid reaction and is nearly completed within the first few minutes after mixing. The union between virus and antibody is quite stable under physiological conditions. The rate of neutralization is dependent on the ratio of antibody:virus, and under the condition of antibody excess there is no persistent fraction of unneutralizable virus particles. During the process of neutralization in a system containing excess antibody, more than one antibody molecule combines with each virus particle. The progressive inactivation of virus with time reflects further reactions within the rapidly established virus-antibody complexes rather than further virus-antibody union.

Electron microscopy of HeLa cells infected with agents of the adenovirus (APC-RI-ARD) group

As previously reported 1 patterns of regularly arranged particles appear in the nuclei of the host cells during the growth of a virus belonging to the adenovirus group (type 5 according to Huebners scheme3). Our finding s have recently been confirmed by Har/ord and co-workers 3 as well as by Morgan and collaborators 4. The study of the cellular changes and the occurrence of particles has been continued and related to the growth curve of the virus. Similar changes have in addition been obse~vefl after infection with a type 3 strain of the same virus group, i. e. the type used by Har/ord and Morgan.

Aspects on the variability of progressive multifocal leukoencephalopathy.

SummaryIn 7 cases of progressive multifocal leukoencephalopathy (PML), five with papova-like viral inclusions, the clinical and neuropathological features varied both within the group and in relation to the accepted, uniform pattern of the disease. Two were „spontaneous” and unrelated to any disease. One ran a protracted, remitting course, and in another the disease appeared stationary. From different points of view the differential diagnosis of multiple sclerosis was considered in these two cases. Two or three were subclinical, a variety which may be more common than hitherto recognized. Pronounced asymmetry in the distribution of lesions appears to be diagnostic interest in this disease, which would be expected to involve the brain in a generalized manner. The occurrence of atypical astrocytes, regarded as a striking feature of old lesions, was unimpressive except in two cases. These two cases on the other hand showed a glial reaction, in some respects simulating a glioma. This was deemed of particular interest in connection with an infection with the papova-group of viruses which is used experimentally to induce tumour. Recent results of virological research in this field can be expected to provide new and better means to study the virus, its occurrence in man and its possible role in PML.

Hospital Outbreak of Adenovirus Type 3 Infections

The clinical and virologic aspects of 38 infections with adenovirus type 3 are described. The material includes 9 patients, admitted directly to the hospital and 11 cases resulting from contact with them, as well as 18 nosocomial infections. A striking difference seems to exist between these groups with respect to the incidence and intensity of the clinical symptoms. The nosocomial outbreak was largely limited to one room, where the patients were systematically examined for virus and antibody occurrence with subsequent correlation to clinical symptoms. It seems possible to draw the following conclusions from the investigation, in contrast, to a certain extent, to those reached by other investigators: