Studies on the pathogenesis of monkey pox

Summary Monkey pox virus (MPV), titrated intramuscularly in cynomolgus monkeys provided a 50 per cent infectivity endpoint of 10^–5.8. All infected animals developed monkey pox. Three of 4 sentinel control monkeys developed monkey pox; one experienced subclinical infection. Viremia intervenes between the 4th and 7th days, and may persist for 4 or 5 days post-eruption, even after appearance of HI antibodies. MPV multiplies in the substance of the inoculated muscle. During the pre-eruptive stage of infection this virus is detected earliest in tonsil and spleen, and shortly thereafter in bone marrow and regional lymph nodes. During the early post-eruptive period, in addition to large concentrations of MPV in these same tissues, the virus is regularly found in cutaneous lesions, some-what less regularly in kidney, and very much less regularly in other tissues. Specific antibodies are raised during infection; HI antibodies are less enduring than CF or neutralizing antibodies. Monkeys convalescent from MPV are immune to challenge with vaccinia, but are fully susceptible to Yaba tumor virus.This investigation was supported by Public Health Service Research Grant AI06263 from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, U.S.A.Research Career Awardee No. K6-AI-13976, National Institute of Allergy and Infectious Diseases, NIH.     

Experimental pathogenesis of buffalo pox virus in rabbits: clinico-pathological studies

Buffalo pox virus produced typical pock lesions on the skin of rabbits at the site of primary inoculation following an incubation period of 48-72 hr. Gross lesions in internal organs, characterized by focal or diffuse necrotic areas on lung, liver and spleen were seen from day 5 post-inoculation (p. i.). Isolated lesions of approximately 2 mm diameter appeared in skin, stomach, intestine and uterus from day 7 p. i. Histopathological changes, i. e. intra-alveolar and intra-bronchial haemorrhages were seen in lungs and severe fatty changes were found in the liver. Multinuclear cells were detected in liver during recovery. Virus particles were demonstrated by electron microscopy in skin, lung, liver and spleen lesions.     

Total haemolytic complement profile in chicks following fowl pox vaccination or infection

Total haemolytic complement levels were assessed in normal, fowl pox-vaccinated or infected chicks using radial immune haemolysis up to 28 days post-treatment. Significantly lower values of total haemolytic complement were recorded 7-21 days post-vaccination or 21 days post-infection as compared to controls (p less than 0.05). The differences between intervals, the influence of the period of treatment were also significant, but the vaccinated chicks did not differ significantly from the infected ones (p less than 0.05). It is concluded that lower circulating levels of total haemolytic complement may be due to deposition of complement at the sites of virus replication.     

T cell virological synapses and HIV-1 pathogenesis

Human immunodeficiency virus type 1 is the cause of a modern global pandemic associated with progressive acquired immune deficiency. The infection is characterized by the loss of the primary target of viral infection, the CD4+ T cell. The measurement of plasma viremia in patients can predict the rate of CD4+ cell decline; however, it is not clear whether this cell-free plasma virus represents the engine that drives viral spread. Active viral replication is mainly observed within lymphoid tissues that are hotbeds of cell–cell interactions that initiate and organize immune responses. It is well established that cell–cell interactions enhance viral spread in vitro. Dendritic cell–T cell interactions, which lie at the heart of adaptive immune responses, enhance viral infection in vitro. Interactions between infected and uninfected CD4+ T cells are a dominant route of viral spread in vitro and are likely to play a central role in viral dissemination in vivo. Future studies will test existing paradigms of HIV-1 dissemination to determine whether virus-transmitting contacts between infected and uninfected T cells called virological synapses are the dominant mode of viral spread in vivo. Here, we review the status of our understanding of this mode of infection with a focus on T cell–T cell interactions and examine how it may explain resistance to neutralizing antibodies and or the generation of genetic diversity of HIV.     

The pathogenesis of fowl thyphoid. The influence of anaemia and erythrocyte clearance on the susceptibility of the fowl to bacterial endotoxin

The possible influence of anaemia, and other related patho-physiological factors known to occur in fowl typhoid, on the susceptibility of the chicken to Salmonella gallinarum endotoxin were investigated. It was shown that anaemia per se did not increase susceptibility of the chicken to injected endotoxin. However, prior intravenous administration of either in vivo modified chicken or heterologous (rabbit) erythrocytes, or intramuscular injection of phenylhydrazine hydrochloride markedly decreased the LD₅₀ of the subsequently injected endotoxin. It is suggested that this increase in susceptibility to endotoxin was due to a blockaded reticulo-endothelial system, resulting from increased erythrophagocytosis of the foreign and altered erythrocytes.These findings were discussed in relation to the pathogenesis of S. gallinarum infection in chickens.     

The detection of cytotoxic lymphocyte activity in chickens infected with infectious bronchitis virus or fowl pox virus

A cytotoxic lymphocyte assay, using cells that adhered to plastic as the target cells and neutral red as the indicator for lysis, was applied to chickens infected with either infectious bronchitis virus or fowl pox virus. Both target and effector cells were derived from the same bird. Cytotoxic lymphocytes were generated in birds infected with either virus. The activity was confined to cells of the spleen after initial immunisation, but could be detected in white cells from the blood after challenge at a peripheral site, with both virulent and avirulent virus strains. It is likely that the cytotoxic cells are T-lymphocytes. The cytotoxic assay system used was an economical and convenient method for chickens which overcame the need for inbred lines of birds.     

Studies on the pathogenesis of Acanthamoeba-associated meningoencephalitis

100 indoor swimming pools were examined for the presence of free-living amoebae. Limax amoebae of the genus Acanthamoeba could be isolated from 34 samples. Naegleria spp. were not present. After axenic cultivation the pathogenicity in mice was tested. Histological as well as immunohistological procedures were compared in order to identify the amoebae in brain sections and to clarify the route of infection. The results indicate a direct invasion of the central nervous system by acanthamoebae via the nasal mucosa and the olfactory bulb.     

Electron microscopical and virological studies of chicken thrombocytesin vitro infected with fowl plague virus (FPV)

Immediately after the adsorption period about 60% of the thrombocytes have phagocytized virus particles. About 2/3 of these cells contain numerous virions and are morphologically severely damaged. In the remaining morphologically not altered third of the thrombocytes only few virus particles can be encountered within vacuoles. After 7 h of incubation all virus containing cells are uniformly damaged, aggregates have become more frequent, and virus particles are mostly found within the extremely dilated perinuclear space. About 20–30% of the thrombocytes remain unchanged and free of virus even after 10 h of incubation. Virological studies show an increase of virus-specific activities starting between 1 and 3 h p.i.

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Zusammenfassung Unmittelbar nach der Adsorptionszeit haben ca. 60% der Thrombocyten Viruspartikel phagocytiert. Etwa 2/3 dieser Zellen enthalten zahlreiche Viruspartikel und sind morphologisch bereits stark verändert. Das übrige Drittel enthält nur wenige Viruspartikel innerhalb cytoplasmatischer Vacuolen und ist morphologisch unverändert. Nach 7 stündiger Inkubation sind alle virushaltigen Thrombocyten gleichartig verändert, Aggregatbildung wird häufiger beobachtet, und die Viruspartikel sind vorwiegend im extrem dilatierten perinucleären Raum zu finden. Etwa 20–30% der Thrombocyten sind auch noch nach 10 stündiger Inkubation unverändert und enthalten kein morphologisch nachweisbares Virus. Virologische Untersuchungen ergeben einen Anstieg der virusspezifischen Aktivitäten, der zwischen 1 und 3 Stunden p.i. beginnt.

     

In ovo infection with an avian leukosis virus causing fowl glioma: viral distribution and pathogenesis

We have previously isolated an avian leukosis virus (ALV) from a chicken affected with so-called fowl glioma. A resistance-inducing factor test indicated that the isolate was classified into a subgroup A. The distribution and pathogenicity were investigated in C/O specific pathogen free chickens infected in ovo with this virus. Histologically, 11 of 12 (92%) infected birds had non-suppurative encephalitis and three birds (25%) showed the characteristic nodules of fowl glioma at 50 or 100 days of age. Non-suppurative myocarditis with matrix inclusions and atypical myocytes were also noted in nine (75%) of the birds and the ALV antigens were immunohistochemically detected in various general organs as well as the central nervous system and heart. The semi-quantitative determination of the proviral DNA and viral RNA supported the immunohistochemical results and indicated that the virus was likely to replicate especially in myocardial fibres. The isolated ALV failed to induce other neoplastic lesions in this line of chickens within the experimental period of 100 days, despite the broad tissue tropism throughout the body. These results confirmed that this virus was able to induce glioma in embryo-inoculated chickens.