2. The antiviral effect of Astragalus membranaceus on interferon was studied in a pioneering way. It was found that Astragalus membranaceus could inhibit the propagation of some viruses, induce interferon, increase the activity of NK cells, promote the production of sIgA level in 19S antibody-forming cells, and prolong the survival time of diploid cells in vitro. Clinically, it is confirmed that Astragalus membranaceus can prevent colds, and the synergistic effect of Astragalus membranaceus and interferon is found.
3. It was found that human umbilical cord blood leukocytes have strong ability to induce interferon, and a high-yield virus strain NDV-F was screened out, and finally a clinical interferon preparation was developed.
4. He developed a series of genetically engineered interferon products, including α 1b, α2a, α2b, γ and other subtypes, among which the recombinant α 1b and α2a interferon obtained the national new drug certificate in 1992. Recombinant interferon α 1b is a new drug product pioneered in the world and the first genetically engineered polypeptide drug in China.
5. Prokaryotic high-efficiency expression vectors pBV220 series and pBV320 series universal high-efficiency expression vectors were successfully constructed.
6, interferon research
Comrade Hou Yunde's research on interferon began with the research on parainfluenza virus. As early as the late 1950s, when I was in the Soviet Union, I found that Sendai virus had different varieties and proved its pathogenicity to people. The acute cell fusion phenomenon of virus in monolayer cell culture was found, and its mechanism was clarified. Later, when it developed into an important means of genetic research in the 1970s, his related works received extensive attention. Because of his outstanding achievements in scientific research, the Ministry of Higher Education of the former Soviet Union surpassed the associate doctor's degree and directly awarded him the Soviet doctor's degree in medicine. After returning to China, he isolated parainfluenza viruses I, II and IV in China.
In the early 1970s, he creatively studied the antiviral effect of Astragalus membranaceus on interferon, and found that Astragalus membranaceus can inhibit the propagation of some viruses, induce interferon, increase the activity of NK cells, promote the production of sIgA by antibody-forming cells of 19S, and prolong the survival time of diploid cells in vitro. Clinically, it is confirmed that Astragalus membranaceus can prevent colds, and the synergistic effect of Astragalus membranaceus and interferon is found.
In the middle and late 1970s, Comrade Hou Yunde made an in-depth study on the induction and purification of interferon in human leukocytes, and found that human umbilical cord blood leukocytes had strong interferon induction ability, and a high-yield virus strain NDV-F was selected, and finally a clinical interferon preparation was developed. 1979, he discovered the translation system of interferon mRNA in African crucian carp oocytes. Because of its simple operating system, it was highly praised by the international interferon conference that year, and then he was selected into the famous enzymology method series. 1982 published a paper on the cloning and expression of IFN-α cDNA, which became one of the pioneering documents of genetic engineering research in China. Subsequently, in 1983, he successfully fused α 1 interferon protein with TGATG sequence. 1984, he was studying the expression vector of recombinant interferon gene. 1987, he and his students formed a series of temperature-controlled prokaryotic high-efficiency expression vectors pBV220, which have been widely promoted throughout the country. In 1990, a series of universal and efficient expression vectors of pBV320 with prokaryotic enhancer-like sequence were established. After years of continuous efforts by 10, he developed a series of genetically engineered interferon products, including α 1b, α2a, α2b, γ and other subtypes, among which the recombinant α 1b and α2a interferon obtained the national new drug certificate in 1992. Recombinant interferon α 1b is a new drug product pioneered in the world and the first genetically engineered polypeptide drug in China. Compared with foreign similar products, it has the advantage of less side effects. Therefore, it won the first prize of 1993 National Science and Technology Progress Award. Five new drug certificates of genetic engineering products have been obtained.
In recent years, outstanding achievements have been made in gene modification of interferon, targeted interferon, pregnancy interferon and development of interferon alleles in China human genome. 1992, he discovered, cloned and expressed two new alleles of α 1 interferon gene in China, which further proved that the newly discovered α 1c/d gene was dominant in some China populations. In 1987- 1992, he successively obtained the α 1/86D interferon mutant with obviously improved activity and the fusion protein of γ interferon and epithelial growth factor through genetic modification. 1992 cloned and expressed China human interferon omega gene, which may be related to reproductive physiology, and developed tumor cell-oriented gene in 1992. These efforts enable China's interferon research to keep up with the international frontier trend and make innovations. Because of its pioneering contribution to the genetic engineering of interferon in China, he was elected as the representative of China, director of the International Interferon Association, for two consecutive years.
7. Study on the genome structure and function of vaccinia virus.
Vaccinia virus is the largest animal virus, and the study of its genome structure and function is an important topic in virology, which has important theoretical and applied significance. As early as 1984, he constructed the gene library of vaccinia virus vaccine strain (Tiantan strain) in China. After 10 years' efforts, the whole genome of the virus (189,274 274kb) has been sequenced and analyzed, which is the largest complete genome sequence in China at present, and many important discoveries have been made. 1985, he first reported the HindⅲP fragment of vaccinia virus genome in the British Journal of General Virology, which supplemented and revised the conclusions of foreign scholars, and was subsequently confirmed by other foreign scholars. 1989, he discovered that vaccinia virus hemagglutinin is a new member of immunoglobulin superfamily, which is the first report that a virus protein with known function belongs to this family. This work was first verified by colleagues in Oxford University, England, and recommended by Dr. Williams, the authority of immunoglobulin superfamily, to the American Journal of Experimental Medicine for publication without experiment. Subsequently, Dr. Moss (National Institutes of Health), Dr. Oldstone (Scripps Clinical Research Foundation) and Dr. Wiley (Harvard University), who studied the molecular structure of HLA, and other relevant international authoritative scientists confirmed this discovery and spoke highly of it. Later, British and American scholars continued to develop on the basis of this work, and found more immunoglobulin superfamily members in vaccinia virus and other vaccinia virus proteins. The research results are considered to be of great enlightening significance to the study of the origin and evolution of viruses and the relationship between viruses and hosts, and are pioneering work in this field. 1990, he found that the hind ⅲ k fragment of vaccinia virus encodes a serine protease inhibitory protein, which may be related to the virulence of vaccinia virus. 1992, he found that the genome sequence of vaccinia virus vaccine strain in China was quite different from that of Copenhagen strain abroad, which provided important clues for comparing and clarifying the virulence mechanism of vaccinia virus. The above research results show that the research on the genome structure and function of vaccinia virus strains in China led by him has a high academic status in the world.
8. Cloning and analysis of genomes of other medical viruses
He isolated and cloned a human papillomavirus type 6 from the wart tissues of women in China, and identified it as a new species in the world by sequencing. He expounded the viral etiology of chronic cervicitis and proved that papillomavirus 16, herpes simplex virus 2 and cytomegalovirus are closely related to the pathogenesis of chronic cervicitis. Herpes simplex virus type 2 genome gene library. The laboratory has developed a variety of genetic engineering cytokines and lymphatic factor, which greatly promoted the industrialization of genetic engineering products in China.
Comrade Hou Yunde has published more than 250 scientific papers in magazines at home and abroad. There are 7 major works and 4 national achievements at or above the ministerial level/kloc-0. 198 1 edited Interferon and its Clinical Application, which is the first monograph on interferon research in China. This book has both theoretical depth and close connection with clinical practice, and also summarizes the research results of Chinese scholars. It was once rated as 1978- 198 1 national excellent science and technology. The book Principles and Methods of Virus Genetic Engineering (65438-0985) edited by him is the first monograph on genetic engineering technology compiled by Chinese scholars based on domestic experience, which plays an important role in promoting the application of genetic engineering technology in medical virology in China. 1990, he wrote all the chapters of Molecular Virology, with a great professional span. This monograph of1100,000 words systematically introduces the molecular structure and functions of viruses in various families, summarizes the research achievements at home and abroad and the author, reflects the international research progress of molecular virology in the 1980s, and is also the most comprehensive and systematic monograph on virology in China. 1994 10 the third Asia-Pacific conference on medical virology affirmed his outstanding contribution in medical virology and awarded him an honorary award.
Academician Hou Yunde has been engaged in medical virology research for 50 years. Great achievements have been made in the research on the genome structure and function of cytokines such as interferon and vaccinia virus, which has made great contributions to the development of medical molecular virology and biotechnology in China. Published about 400 scientific papers in domestic and foreign magazines; 9 major works at or above the ministerial level and more than 20 achievements; Among them, there are 7 first prizes 1 for national scientific and technological progress and 7 second prizes; Second prize of national natural science 1, first prize of scientific and technological progress of Ministry of Health 10. Obtained 7 national new drug certificates.