Virus

VIRUS (Lat. virus-venom), a term used in a broad sense to denote any living causative agent of infectious diseases and which has replaced the older term 'contagium vivum' (Kircher). For example, one speaks of: V. of typhoid fever, V. of diphtheria. But more often this word is used to denote still unknown living causative agents of some contagious diseases (for example, one speaks of V. of epidemic encephalitis) and, especially, to denote those causative agents which are capable of passing through bacterial filters (for example, V. of rabies). In the latter case, one speaks of a filterable virus. P. Rosen. Filterable virus, at the present time, the name for such causative agents of infectious diseases which are distinguished by their extremely small size, as a result of which they are little or completely inaccessible for study through the microscope and easily pass through the pores of filters (Chamberland and Berkefeld candles, etc.). The group of F.V. appears to be quite heterogeneous and does not lend itself to a general definition, although within this group a considerable number of representatives are known, united by related characteristics. The difficulty of precise characterization of F.V. is increased by the discovery in recent years of filterable forms in ordinary microscopically visible microbes, for example, in bacilli of tuberculosis, typhoid fever, dysentery, plague, in trypanosomes and spirochetes. On the other hand, the causative agents of some diseases, until recently considered typical F.V., upon closer study proved to be filterable forms of spirochetes, such as, for example, the causative agent of Weil's disease (Inada and Ito, Fromme and Uhlenhuth) and of epidemic parotitis (Kermorgant). Undoubtedly, among those that still retain the name F.V., some will also prove to be filterable forms of microscopically visible microorganisms. Despite all the difficulty of drawing sharp boundaries between the concepts of F.V. and 'filterable form' of a visible microbe, which, according to the terminology of Charles Nicolle (Ch. Nicolle), is called 'inframicrobe,' or, according to Friedberger, 'cryptoantigenic virus,' nevertheless for F.V. a number of characteristic biological distinctions can be given, inherent to a greater or lesser degree in all representatives of this group. Thus, in regard to size, the majority of F.V. represent extremely small structures, measurable in submicrons and capable of penetrating through the finest pores of Chamberland filters, which, according to Bechhold, in their highest limit have pore sizes of 0.17-0.008 µ. According to Levaditi, viruses of smallpox, herpes, and rabies are even capable of ultrafiltration through a collodion bag impassable for alexin (see.) sera, certain enzymes, and toxins. Kaolin, animal charcoal, and cell suspensions adsorb F.V. Other F.V. represent, in the opinion of some researchers, larger structures and already stand within the limits of ultramicroscopic, even microscopic visibility, which allows to some extent to judge their morphology. According to Borrel, for example, the virus of pleuropneumonia represents the smallest coccus (Asterococcus mycoides), and according to the data of Bordet - a microbe possessing great polymorphism. The relationship of individual F.V. to various physical and chemical influences is very diverse. Drying, for example, is fatal to many of them (foot-and-mouth disease, swine plague, plague of cattle), is easily tolerated by others (viruses of smallpox and herpes). Some V. are capable of remaining in a dried state for several months and even years (V. of herpes and mosaic disease of tobacco). The properties of the medium have a great influence on the stability of F.V. In protein media, apparently, proteins have a protective effect on them, and their stability increases. In relation to temperature influences, F.V. do not show great stability and usually perish at t° around 55-60°. A considerable number of F.V. show greater resistance to glycerin, which is fatal to microbes of bacterial origin, in view of which this property is by some researchers made the basis for contrasting F.V. with ordinary microbes and, in particular, with the filterable forms of the latter ('inframicrobes' of Nicolle). Many F.V. perish from the action of bile, bile salts, and saponin, which brings them closer to the group of protozoa (Protozoa). Only a small part of the F.V. known at the present time have been obtained in pure culture on artificial nutrient media (virus of pleuropneumonia). This circumstance, in the eyes of some researchers (Menze, Levaditi), can serve as one of the grounds for their fundamental opposition to ordinary microbes (bacteria and Protozoa), which are more or less easily cultivated on laboratory nutrient media. Apparently, the difficulty of obtaining F.V. in cultures outside the organism is a reflection of their intracellular (endocellular) parasitism. Attempts to grow them in tissue cultures, predominantly those affected by them, give every reason to hope for success. Experiments have shown that the virus of smallpox is capable of developing in tissue cultures of the cornea, skin, and testicle. Levaditi succeeded in maintaining the virus of rabies and poliomyelitis in a viable state in ganglion cells on monkey plasma for quite a long time (for example, the virus of rabies for up to 53 days). In regard to morphology, a very characteristic feature of most F.V. is the formation of special intracellular inclusions, usually located near the nucleus of the cell and often having pathognomonic significance. To such inclusions, found predominantly in tissues of ectodermal origin, belong Negri bodies in rabies, Guarnieri bodies in smallpox, Prowazek bodies in trachoma, inclusions in herpes, fowl pox, etc. In close relationship with the intracellular inclusions are often found the smallest coccalike formations. Lipschutz looks upon these formations as parasites sui generis and gives them the name 'Strongyloplasma.' The intracellular inclusions, however, he considers as degenerative changes of the cell or as its reaction to the F.V. Prowazek unites all F.V. that show intracellular inclusions into a special group 'Chlamydozoa' and also considers these inclusions as a product of the cell's reaction to the parasite. In recent years, there is a tendency to recognize these inclusions as one of the developmental stages of the parasite. Levaditi, for example, considers the parasite of rabies a microsporidian (Glugea lyssae) and looks upon Negri bodies as one of the stages of its development ('pan sporoblast'). He holds the same view of the inclusions in herpes. Some researchers also look upon Guarnieri bodies as one of the developmental stages of the smallpox causative agent. On the other hand, inclusions in a number of diseases are considered as degenerative changes of the cell. This includes, for example, oxyphilic degeneration in herpes and encephalitis. F.V. are capable of causing in humans and animals both general and strictly localized diseases. The latter circumstance is clearly conditioned by a pronounced affinity (tropism) of certain viruses for certain tissues and organs. This tropism is sometimes expressed so sharply that the introduction of the virus into any of the organs leads to its accumulation exclusively in those to which the virus possesses maximum affinity. In herpes, for example, the introduction of the virus into a rabbit in any of its parenchymatous organs leads to the accumulation of the virus in the central nervous system and adrenal glands, with its complete absence in all other organs (Teissier, Gastinel, Reilly). For smallpox and contagious epithelioma (epithelioma contagiosum) of birds, the pronounced tropism of F.V. for the skin is characteristic. Such selective (elective) orientation toward certain organs is also characteristic to a greater or lesser degree of other F.V., which gave Lipschutz the opportunity to base their classification on this property. Thus, according to Lipschutz, one distinguishes viruses causing: 1) general diseases (plague of cattle, swine plague, plague of birds, Pappataci fever, etc.); 2) diseases with predominant localization in certain organs: a) causing localized diseases of the epidermis and epithelium (molluscum contagiosum, warts, trachoma); b) dermotropic viruses (smallpox, alastrim, varicella, contagious epithelioma of birds, foot-and-mouth disease, febrile herpes, herpes zoster); c) neurotropic viruses (rabies, poliomyelitis, canine distemper, lethargic encephalitis of man, infectious encephalomyelitis of horses); d) hemotropic viruses (leukemia of fowls, pernicious anemia of horses); e) organotropic viruses (pleuropneumonia of cattle, virus myxomatosum of rabbits, agalaxia contagiosa). In recent years, certain changes have been made in this classification. Through the work of Lipschutz, Menze, and especially Levaditi, the property of some dermotropic viruses, under certain conditions, simultaneously with the external ectodermal covering (skin, cornea), to affect the internal segment of the ectoderm (central nervous system) has been noted, in view of which these viruses are now isolated by some authors into a special group of 'neurotropic ectodermoses.' This group is closely connected by gradual transitions with purely neurotropic viruses.

In order of increasing neurotropism, Levaditi includes smallpox, herpes, encephalitis, rabies, and poliomyelitis. To ectodermoses, Levaditi contrasts mesodermoses, i.e., diseases of organs derived from the embryonic mesoderm, caused by visible parasites—bacteria, fungi, spirochetes, and Protozoa. According to Levaditi, there are fundamental differences between these two types of diseases. The causative agents of mesodermoses are visible, capable of cultivation on artificial nutrient media, and create phagocytic, antitoxic, and bactericidal immunity in the body. The causative agents of ectodermoses are invisible, non-cultivable, and the immunity they produce is purely local and cellular. However, Levaditi's views have not gained universal acceptance and are largely disputed. Diseases caused by viruses can sometimes produce very strong and long-lasting immunity, which in some cases, such as with smallpox, can be very significant. In terms of prevention, for most viral diseases, one must practically resort almost exclusively to active immunization, for which weakened live virus is usually used. For immunization against smallpox, this is achieved by using virus adapted to another species (cowpox); for rabies, the virus is weakened by drying or dilution. For preventive vaccinations against contagious bovine pleuropneumonia, unweakened virus is used, but for its introduction, an organ is used in which the progression of the virus into the body is significantly slowed due to anatomical conditions (vaccination in the tail dock). A number of researchers have indicated that killed virus can also immunize, for example, heat-killed smallpox virus, the so-called vaccinogen (Torikata, Nakagawa, Takakki). However, its immunizing properties proved to be low. Attempts to use carbolyzed vaccines against rabies (Fermi) also showed that killed virus is significantly inferior to live virus in immunizing properties. Passive immunization in diseases caused by viruses has found much less application and gives good results only in a few diseases (rinderpest). Sero-vaccination has found much wider application (foot-and-mouth disease, rabies). When immunizing animals, virucidal (virus-killing) properties are found more or less constantly in their sera. Other immune properties are observed in sera much less constantly, and for many infections, their presence has not yet been proven. Nevertheless, alexin-fixing properties of sera have been found for a number of diseases (smallpox, varicella, and herpes zoster). The results obtained for rabies and herpes are less convincing. The same is true of the precipitating properties, which have so far been found in only a few diseases (smallpox). The weak ability to produce immune serum properties and their inconsistency lead some scientists (Levaditi) to deny their importance in building immunity and to seek the cause of the latter in the local, cellular insusceptibility of virus-sensitive tissues. In favor of this hypothesis is the sometimes sharply expressed ability of immune organs to destroy the virus. Virus fixe, see Rabies.