Springer Science and Business Media LLC

Experiments in the mouse model of herpes simplex virus (HSV) infection involving the intact genital mucous membranes as inoculation site yielded the following results. In untreated mice the extent of latency was correlated with the degree of peripheral virus replication. This correlation could not be observed when the course of infection was interrupted by chemotherapy, interferon, or passive immunization. Acyclovir had little effect on peripheral virus multiplication, but markedly reduced latent ganglionic infection. As acute ganglionic infection and virus concentration in the spinal nerves were already reduced, acyclovir is assumed to inhibit either virus penetration into the nerve endings or virus replication in the ganglia. Interferon apparently has an active role in the elimination of virus infected cells from the ganglia, as its effect was restricted to a reduced rate of latency and of lethality. Passive immunization with antiserum led to similar results as ACV-treatment. While lacking a pronounced effect on virus replication in the mucous membranes, specific antibody was found to influence both virus elimination from the ganglia, and conversion from productive to latent ganglionic infection. Immune lymphocytes proved to be the only agent capable of suppressing peripheral infection, thereby inhibiting the neural spread of the virus. These results suggest that the decrease in latency may result from modulations occurring at different stages in the course of infection.

Bệnh đậu mùa là bệnh đặc hữu tại Thượng Hải và cho thấy các chuyển động định kỳ theo năm. Tỷ lệ mắc bệnh và tử vong cao nhất xảy ra trong các tháng mùa đông (tháng 12, tháng 1, tháng 2); sau đó, tỷ lệ này liên tục giảm với một số đợt phục hồi nhỏ cho đến cuối mùa hè (từ tháng 8 đến tháng 9), khi mà tỷ lệ mắc bệnh và tử vong đạt mức thấp nhất; từ cuối thu, con số lại tăng nhanh hướng tới đỉnh điểm mùa đông. Nhiều yếu tố khác nhau có thể là nguyên nhân cho chuyển động định kỳ này. Ngoài sự chuyển động theo năm, các hình thức chu kỳ khác của dịch bệnh (các dao động đều đặn về tỷ lệ mắc hoặc tỷ lệ tử vong) không được ghi nhận trong 20 năm quan sát vừa qua.

Cysteine proteases are one of the major classes of proteolytic enzymes involved in a number of physiological and pathological processes in plants, animals and microorganisms. When their synthesis, activity and localization in mammalian cells are altered, they may contribute to the development of many diseases, including rheumatoid arthritis, osteoporosis and cancer. Therefore, cysteine proteases have become promising drug targets for the medical treatment of these disorders. Inhibitors of cysteine proteases are also produced by almost every group of living organisms, being responsible for the control of intracellular proteolytic activity. Microorganisms synthesize cysteine protease inhibitors not only to regulate the activity of endogenous, often virulent enzymes, but also to hinder the host’s proteolytic defense system and evade its immune responses against infections. Present work describes known to date microbial inhibitors of cysteine proteases in terms of their structure, enzyme binding mechanism, specificity and pathophysiological roles. The overview of both proteinaceous and small-molecule inhibitors produced by all groups of microorganisms (bacteria, archaea, fungi, protists) and viruses is provided. Subsequently, possible applications of microbial inhibitors in science, medicine and biotechnology are also highlighted.