Studies on the pathogenesis of rinderpest in experimental cattle II. Proliferation of the virus in different tissues following intranasal infection

Abstract

The pathogenesis of rinderpest virus was studied in twenty-nine grade cattle, which were infected by the intranasal route with a virulent strain of virus recently isolated in East Africa (RGK/1). These animals were killed or died at intervals of 1–16 days after infection and a number of tissues from each of them (usually 21) was titrated for virus infectivity in monolayer cultures of primary bovine kidney cells.Temperature reactions were first detected on the 3rd to 5th days (mean 4·1), mouth lesions on the 6th to 9th and diarrhoea on the 8th or 9th days, following infection. The course of the disease was divided into four phases, viz. incubation (days 1–4), prodromal (days 5–7), mucosal (days 8–12) and early convalescence (days 13–16). Virus proliferation in different tissues was related to these clinical phases, detailed results being presented in tabular and graphical form.No primary multiplication was detected in the nasal mucosa but virus was demonstrable within 48 hr. in its associated lymph nodes. Low-level viraemia began on the 2nd or 3rd days after infection and generalization had occurred by the end of the incubation period. The virus had established itself at this time throughout the alimentary tract and, sometimes, in the lungs.The prodromal phase was characterized by plateaux of high virus titres in the lymphopoietic and lympho-epithelial tissues; there was a descending gradient from the cephalic nodes to the superficial lymph and haemolymph nodes of the body, to the visceral lymph nodes and spleen. There was a similar gradient in the titre of virus in the mucosae of the gastro-intestinal tract—from caecum to colon, to ileum and pylorus. Virus first appeared in the turbinate mucosa on the 5th day, post-infection and lung titres were high towards the end of this period. Some virus proliferation may have occurred in the liver, but none was certainly demonstrable in the kidney, myocardium or brain.The mucosal phase began with continuing high titres of virus in all the major sites of proliferation, but a decline set in from the 9th day onwards. This at first involved the cephalic lymph nodes but soon extended to the spleen and other lymphopoietic tissues. It was most delayed in lympho-epithelial structures such as the tonsil, lung and gastro-intestinal mucosae. It was suggested that the decline in virus titres was due to the destruction of susceptible cells, accompanied by the local production and later circulation of antibody. Neutralizing antibody was present in the serum on and after the 9th day.During the early convalescent period virus had disappeared from four animals, with the exception of one recovery from the lung tissue. Antibody titres were high during this time.These results were discussed with reference to previously existing information on the distribution of rinderpest virus in infected cattle. An attempt was made to correlate them with published information on the pathogenesis of human measles and canine distemper. The data were also used to explain some previously reported observations on the excretion of rinderpest virus by experimentally infected cattle.This study would not have been possible without the enthusiastic co-operation of Messrs C. S. Rampton, A.I.M.L.T., R. F. Staple, A.I.M.L.T., and R. Pillinger, F.I.M.L.T., in organizing and carrying out a very considerable number of laborious titrations. Dr B. Liess helped with some of the animals killed at earlier stages of the infection. Our junior African staff gave invaluable assistance with their careful and efficient handling of many thousands of tissue cultures; amongst them we should particularly like to mention Mr Francis Ngugi and Mr Harrison Agili.This paper is published with the permission of the Director, E.A.V.R.O., Mr H. R. Binns, C.M.G., O.B.E.

Studies on the pathogenesis of rinderpest in experimental cattle: IV. Proliferation of the virus following contact infection

“…amounts into each of five tubes of primary calf kidney (BK) cells. It was found previously (Plowright, 1964;Taylor & Plowright, 1965) that, for solid tissues, dilutions lower than 10-2 could produce cytotoxic changes in BK cells and hence this was the highest concentration inoculated.…”

“…Blood was collected in every case for viraemia estimation (Plowright, 1964) and for separation of serum.…”

“…The technique for collection of solid tissues was as already described (Plowright, 1964). The pharyngeal mucosa was obtained, in all except four instances, by removing a 2-3 cm.…”

“…9927, when bacterial contamination made it necessary to terminate readings on the 7th day. Titres were calculated as before (Plowright, 1964).…”

“…The technique used in the preparation of tenfold dilutions of solid tissue has already been described; so, also, have the preparation of blood leucocyte fractions and blood dilution series (Plowright, 1964).…”