The growth of some myxoviruses in organ cultures.
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Biomedical subjects
Publications and source records attributed to D A Tyrrell.
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Interferons were discovered from their antiviral effects. It is now known that they are the products of families of genes found in many vertebrate species and that they bind to cell surfaces and produce a range of effects, varying from an antiviral state to increased expression of tissue transplantation antigens, decreased cell division, and modified immune responses, among others. Interferons are induced by exposure to viruses and double-stranded RNA, and one class, gamma interferon, is a lymphokine produced after a mitogenic or antigenic stimulus. The genes for human alpha, beta, and gamma interferons have been cloned and sequenced, and some have been expressed. When given parenterally to humans, interferons cause signs and symptoms such as fever, tachycardia, and malaise, and they may well be responsible for symptoms of this sort in viral infections. Preparations of natural and recombinant alpha interferon have been shown to be active in prophylaxis and treatment of certain viral infections.
Twenty-four adult volunteers were inoculated with nasal drops containing a coronavirus of 229E serotype to determine the differences in the clinical and physiological reactions which occur between clinically infected, sub-clinically infected and non-infected individuals. Thirteen volunteers were clinically infected, 8 had sub-clinical infections and 3 were uninfected. Nasal airway resistance and the temperature of the nasal mucosa increased in all infected subjects both with and without symptoms: the core temperature increased also but to a lesser extent. Mucosal blood flow and nasal secretion increased only in those with symptoms. The albumin content of the nasal secretion increased in the clinically infected, suggesting that it was derived, partially at least, from the circulation. The nasal cycle of variation in airway resistance between the two sides of the nose was observed in all three groups but increased only in those clinically infected.
Measurements of peak flow, vital capacity, FEV1 and flow volume studies were performed in healthy volunteers for 20 weeks following intranasal vaccination with live-attenuated A/Victoria/3/75 recombinants or placebo. Despite differing attenuation of the two candidate strains, no effect on pulmonary function was detected.
It is not yet clear from these recent volunteer studies (8) and from the results of Merigan et al. (14) what the optimal method and schedule for administering HuIFN should be. Taken together, the results with relatively low doses of interferon (1 to 4 X 10(6) units) plus antihistamine pretreatment, and with multiple doses of HuIFN alpha (total 14 X 10(6) units) indicate the need for better methods of delivery. However, it is of interest that protection was achieved by extremely small amounts of HuIFN alpha protein - Merigan (14) used only about 160 mcg. We anticipate that with better supplies of interferon from HuIFN genes cloned in bacteria, we may seek more efficient means of delivery and obtain better protection of volunteers against respiratory virus infections.