THE MOST IMPORTANT TASKS OF USSR MEDICAL VIROLOGY

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• Document Creation Date: December 22, 2016
• Document Release Date: July 14, 2011
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• Publication Date: March 29, 1955
• Content Type: REPORT

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THE MOST IMPORTANT TASKS OF USSR MEDICAL VIROLOGY
Zhurnal Mikrobiologif Epidemiologii,
i lmmunobiolo ii,
Moscow Sep 195 , pp 3_9
V. D. Solcv'yev
V. M. Zhdanov
Among scientific disciplines which deal with infectious diseases, a
prominent place is occupied by medical virology. It is sufficient to recall
that among the most common infectious diseases are such virus infections as
influenza, measles, epidemic hepatitis, poliomyelitis, encephalitides, hernor-
-ha
fcvsrc, pappataci fever, chicken pox, epidemic hepatitis, choriomeningi-
tis
, etc.
During recent yearn the virological institutions which are active in our
country have developed and become stronger. In addition to the Institute of
Virology imeni E. I. Ivar.ovskiy, Academy of Medical Sciences USSR, and other
virological laboratories located in Moscow, important research on virus in-
fection is being conducted at Leningrad, Tashkent, Khar'kov, Kiev, Tomsk,
Alma-Ata, Odessa, Molotov, Yrrevan, and other cities of the Soviet Union.
The organization of virological laboratories at some sanitary-epidemiological
stations has b2-n launched. As th? scop, of the investigations develops,
practical rensrres for the control of virus infections, which are based on
contemporary scientific data, are expanded. For that reason it is expedient
to give a brief review of the most important tasks to be solved by General
and special virology.
In the field of general virology, problems pertaining to the modifiability,
morphology, and biochemistry of viruses and to the experimental chemotherapy
of virus infections comrrand particular attention.
The strict tissue parasitism (intracellular parasitism) of viruses,
which distinguishes viruses from other microorganisms, requires special methods
for the study of their modifiability. Investigations which have been carried
out during recent years established that such biological characteristics as
virulence, antigenic structure, and immunological properties are determined by
the characteristics of the medium [or environment] in which the development of
the viruses takes place.
The most stable property is the antigenic structure of the viruses, which,
as a rule, was found unchanged after passage through the organism of different
animals or cultivation of the viruses in cultures of animal tissues. This
was clearly demonstrated in the examples of the viruses of influenza, tick
encephalitis, epidemic parotitic, and vaccinia. The antigenic structure of even
a relatively ' le virus such us that of influenza, could be changed under
laboratory conditions only by subjecting it to tLe action -f specific immunity
factors. The investigations in question make possible an understanding of such
contradictory phenomena as th-- existence of viruses which function as causative
factors of different diseases but nevertheless have a similar antigenic structure
(e.g., the viruses of tick encephalitides and the viruses of the psittacosis-
lymphogranuloma group), as well as the occurence of several serological types
among the causative factors of identical diseases (e.g., the viruses of influ-
enza and poliomyelitis).
Results which differ from those outlined above were obtaC
tigation of the immunogenic characteristics of viruses. In the case ofethevin-
fluenza virus, these characteristics depend on the species of the animal or the
nature of the isolated tissues used. For that reason, prolonged passages through
mice, chicken embryos, or cultures of tissues derived from these animals [mice
and chickens] bring about an attenuation of the immunogenic properties of the
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strain with respect to human beings. On the other hand, when the virus is
passed through cultures of human tissues
r
i
t
,
p
eserved.
s immunogenic properties are
Passages of the virus of tick encephalitis, Japanese encephalitis
rab or
ies do not bring about a loss of immunogenicity in human beings.
The pathogenic properties were found to be the least stable. These
thepviruses(under beronmentalweakcened SPecificall
established that in the by cultivating
establis process of adaptation of a number of viruses to a was
species of animal the virulence increases with reference to the species
in question and is modified with reference to human beings.
The regularities in the modification of viruses which have been indicated
above standing deserve of these the r closest attention and require further study because under-
egularities and an ability to control them are necessary
prerequisites for the production of live vaccines. Practical application of
the regularities involved has already proved successful in the search for live
vacrtnes, particularly vaccines for the prophylaxis of influenza. There can
be no doubt that further development of the investigations in'question will
form a basis for the.production of live vaccines that are effective against a
number of additional virus infections.
One must also concentrate on investigations dealing with the morphology
and biochemistry of viruses. It must be admitted that research on the morphology
of viruses is not being carried out to an adequate extent. Nevertheless,
investigation of the morphology of viruses and of virus occlusions by means of
electron microscopy and phase-contrast microscopy is of great importance both
for the clarification of the nature of viruses and the diagnosis of virus
diseases.
fins The
Chemicontempcalomotrary
viruses
investigateothet nature principal pthe
causative factors as such. Parallel to this the biochemical processes which
take place during the reaction of viruses with sensitive tissues of the
macroorganism are being investigated.
The first line of research is not being pursued to an adequate extent in
our laboratories. Expansion of this type of work depends on the availability
of the necessary equipment and. requires that serious attention be paid to this
type of research.
Groups of biochemists and virologists who are active under the direction
of V. L. Ryzhkov and V I. Tovarnitskfy are engaged in work of the second type.
Among .investigations carried out by these groups of investigators one may
mention research on the mechanism of the reaction of the influenza virus with
erythrocytes and with the structural elements of the cytoplasm, as well as the
role of the so-called inhibitors. In this work the significance of the func-
tional group of proteins, of the salt cuntert of the medium, 01' th. temperature,
and of other factors was demonstrated. Using the results of the work in
question, simple and promising methods for the preparation of agents used in
laboratory diagnosis have been developed.
Of great interest are the investigations of biochemical processes taking
place during the propagation of pathogenic and nonpathogenic strains of the
influenza virus. It was established that the pathogenesis of experimental
influenza does not depend so much upon the propagation of the virus as on
disturbances of various types of metabolism (carbohydrate, phosphorus, and
protein metabolism) brought about by the pathogenic strains and interfareuce
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The energetic aspects of the Fro 1~ ~''?g to internal organs.
during the process of infection area also being subjectedttoiinvestigation.
This line of biochemical research touches closely upon the pathophysiolog-
ical investigations that deal with pathogenesis and immunity in virus
diseases being carried out in the laboratory of A. D. Ado. In this labora-
tory the action of viruses as specific irritants of the nervous system
is being investigated.
The study of biochemical processes which take place during the inter-
action of viruses with the tissues of the macroorganism is also important
because it opens up possibilities of finding methods which make it possible
Lo influence the process of infection by chemotherapeutic means.
One must emphasize that chemotherapeutic investigations are being
carried out in the USSR on an entirely inadequate scale. Considerable
expansion of work in this field is necessary. The work in question must
include the synthesis of new therapeutic agents and the search for anti-
biotics which counteract virus infections.
We do not consider it possible to delve into general problems of
pathogenesis and immunity in virus infections, assuming that these prob-
Jer's should not be Lietaehed f,om the development of a more general prob-
lem, namely thct of pathogenesis and immunity in infectious diseases
corsid.ered on the basis of I. P. Pavlov's physiological teaching. At
the same time, in working on the latter problem, one must not forget
that the phenomena of pathogenesis and immunity in virus diseases are
so diverse that it is practically impossible to draw on the basis of
the study of individual diseases general conclusions which are valid
for all virus infections. Work on the systematic classification of
viruses is one of the problems of general virology. The publication
of wcrk by V. L. Ryzhkov, Sh. D. Moshkovskiy, and V. M. Zhdanov on
this subject, in combination with the discussion on this problem which
has developed at the Moscow Society of Microbiologists, Epidemiologists,
and Infectionists, as well'as on the pages of the periodical Mikrobiologiya,
will undoubtedly contribute to the development of a unified USSR system-
atization and nomenclature of viruses.
The most important task which confronts Soviet virology is the
practical solution of the problem of influenza. The intensive scientific
work which has been carried out on this subject during recent years at
the Institute of Virology, the Institute of Experimental Medicine, and
the Moscow Institute imeni Mechnikov has culminated in the development,
testing, and introduction into practical use of live anti-influenza
vaccines. Immunization wita these vaccines as become one of the principal
methods for the prophylaxis of influenza. An appropriate place in the
system of measures for the control of influenza must be occupied by the
anti-influenza serum developed by A. A. Smorodintsev at the Institute of
Experimental Medicine and the Institute of Virology. The Investigations
which have been carried out hitherto do not, of course, exhaust the possi-
bilities for the specific prophylaxis of influenza. Further work on the
perfection of available vaccines and sera and of the methods of their
application is required.
One of the aspects of the problem of influenza which remains unsolved
is that pertaining to the diagnosis of the disease and above all, an early
and rapid differential diagnosis of it. As far as methods of early diagnosis
of influenza are concerned, particular attention should be paid to the
reaction of hemagglutination for the detection of the influenza antigen
in washings from the nasopharynx. Although this reaction was proposed f:;r
practical use without adequate methodological preparation, it should not
r.
; ph
,0
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have been forgotten after the extensive but unsuccessful use which had
made of it. There are ade
been
quate reasons for the belief that this reaction
may becensiderably perfected, its sensitivity increased, and the nonspecific
reactions accompanying it suppressed.
Less promising is the reaction of complement fixation, because any method
of diagnosing influenza must be simple and suitable for application on at mass
scale. Serological procedures which enable one to detect increases of the
amount of specific antibodies in the blood remain the most reliable methods for
the laboratory diagnosis of influenza. However, methods of this type are purely
retrospective. Furthermore, in order to apply methods of this type one must
dispose of assorted type antigens (diagnostica) which have been tested and
approved. These antigens must include the principal variants of viruses, i.e.,
A. B. and Al. One must further improve the clinical-laboratory methods for the
diagnosis of influenza (i.e., rhinocytoscopy, testing of the blood) and check
more thoroughly the microscopic methods of investigation (i.e., viroscopy,
investigation of occlusions).
In view of the fact that the progressing modification of the antigenic
structure of influenza viruses which participate in the epidemic process has
been firmly established, observation of strains which circulate among the
population acquires great significance. This ob;;ervatfon must be carried out
to include these strains in the composition of vaccines and diagnostic antigens.
The investi.gcti;,.+s in question must be conducted in different areas of the
country according to a u:,ified plan devised by the Institute of Virology. At
the same time, one must carry out observation on the indices of immunity among
the population. There can be no doubt that the investigations mentioned above,
when combined with epidemiological investigations, will clarify the genesis of
influenza epidemics and thus enable us to set an epidemiological prognosis and
take prophylactic measures in good time.
The problem of acute catarrhs of the upper respiratory tract requires
particular. attention. In this i eld a number of problems have not yet been
solved, although the connection of this group of diseases with weather factors
and with chilling of the body is evident. This applies particularly to cold
catarrhs whin are not complicated by any other condition or complicated solely
by an autogenous infection. Furthermore, it is now known that one often regis-
ters under the classification of acute catarrhs aggravations of chronic patho-
genic conditions of the throat, pharynx, nose, and adjacent regions. Such
aggravated conditions also depend primarily on chilling and colds. Among young
children a considerable portion of contagious catarrhs of the respiratory tract
has a staphylococcus etiology. According to statistical data which have been
accumulated during a number of years, there are fluctuations of the indices of
incidence of acute catarrhs among workers, depending on the branch of industry
in which these workers are active. ThIs testifies to the fact that occupational
conditions ::ave an effect on the incidence of catarrhs. Th? facts that have
been observed i',)r:? a basis for suescquent work on the subject of acute catarrhs
of the upper respiratory tract and make possible developme, of a system
therapeutic and prophylactic measures against this type of affliction.
The so-called atypical or interstitial pneumonias also belong to the group
of virus diseases of the respiratory organs. It is clear that these diseases
do not comprise an etiologically homogeneous group. Some of them have been
found to be Q-fever infections, while others are due to infection with ornithosis.
Solution of the problem of atypical pneumonias will be advanced by the practical
possibilities of differentiating then: by identifying etiologically distinct
forms in the laboratory.
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In order to accomplish this one must develop within the shortest possible
times and introduce into practical use
dia
ti
,
gnos
c antigens for serological
reactions and skin tests. The experimental investigation on epidemic parotitis
which has been conducted at the laboratory directed by A. K. Shubladze made it
possible to check from every standpoint the data obtained earlier by foreign
investigators and to conduct work which sheds new light on many aspects of the
clinical course and epidemiology of this disease. One must expand the inves-
tigations, which have already shown a promise of success, and subject the
virus of parotitis to a more thorough study. On the other hand, the data
which have already been accumulated must be applied practically. These data
will aid in solving the various problems of diagnosis and prophylaxis.
Virologists should also concentrate on still another common infection,
namely measles. Investigations carried out in the laboratories directed by
P. O. Sergiyev and V. I. Ioffe established that it is possible to isolate the
virus of measles and pass it through susceptible animals and chicken embryos.
In Sergiyev's laboratory the characteristics of the virus and its modifiability
have been thoroughly investigated. Work on the development of a live vaccine
against measles has progressed in this laboratory to a considerable extent.
Ioffe has carried out investigations on a minor scale on the use as a vaccine
of a strain grown on chicken embryos. However, the extent of work being done
on measles, and what is more important, the practical application of the results
of research on measles which has been completed, are definitely inadequate.
It is necessary to dispose of reliable methods for the cultivation of,the virus
in order to be able to solve more rapidly the basic problems involved in the
development of an effective live vaccine and the mass production of this vaccine.
In solving these problems it is expedient to consider the experience accumu-
lated in work on the development of anti-influenza vaccines. At the same time
one should not underevaluate the difficulties that confront investigators who
work on measles. These difficulties are connected with the characteristics of
the measles virus. The virus u; measles is strictly adapted to human beings
and is not pathogenic to any e.aerimen~al animals with the exception of simians.
The problem of epidemic hepatitis proved to be still more refractory. Not-
withstanding the great interest in this problem, and the considerable number of
investigations on the subject carried out both in the USSR and abroad, research
on epidemic hepatitis has stopped because no reliable methods of cultivating the
virus or laboratory models for its investigation exist.
Here we have an example of an investigation which has been delayed because
no reliable methods are available, so that the problem in question can not be d. The rateeand history of
virology shows has
depending e on p the at
discovery of
new methods of investigation which facilitated the solution of scientific prob-
lems. It is well known that t~e stud;; of infections for W',Ji:h susceptible
experimental animals were found progressed most rapidly. 1ne use of chicken
embryos for the cultivation of viruses sharply advanced research on a number
of virus infections. This o?ened un new possibilities as far as the production
of the virus vaccines for prophylaxis is concerned. T:ie extensive investigation
to which the viruses of poliomyelitis and the Coxsackie virus were subjected
became possible because the viruses could be passed through newly born mice
and cotton rats.
Viruses for which no susceptible animals could be found, which cannot be
cultivated on chicken embryos, or can be cultivated on this medium only with
difficulty, and for which no indicative reactions aiding in detection have been
found, remain least investigated. To these viruses belong the causative factors
of epidemic hepatitis, of polyseasonal neuroinfections, and of chicken pox.
The viruses of many skin diseases, i.e., pemphigus, psoriasis, herpetiform
dermatitis, etc., also apparently belong to this class. The viruses of human
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tumors definitely belong to it. A characteristic which these viruses have in
common is their strict adaptation to human beings. One must assume that for
the cultivation of these viruses, cultures of human tissues in vitro will serve
as the most suitable medium. The advisability of applying this method has
been demonstrated in the example of other causative factors of diseases which
also affect human beings only, namely influenza and poliomyelitis. However,
the main difficulty in this case will consist in finding a good indicator
reaction which will make it possible to detect the virus in the culture. For
the influenza virus, passage through chicken embryos serves as an indicator
reaction of this type. The virus can be readily detected in the chicken
embryos by the method of hemagglutination. The virus of poliomyelitis, when
cultured in e fibroblast tissue culture in vitro, brings out distinct morpholog-
ical than,-es of a degenerative character. Furthermore, the virus can be de-
tected by passing it through susceptible animals. Such specific indicator
reactions have r.:.t been found for the infections mentioned above. Every effort
mutt be bent to find such reactions.
Important problems must also be solved by virologists in the field of
viral neuroirfections. This refers particularly to poliomyelitis. Significant
progress in the experimental investigation of the virus of poliomyelitis will
make it possible to initiate research on methods for the laboratory diagnosis
of this disease and to develop methods for its treatment and prophylaxis. Some
of the epidemiological characteristics of poliomyelitis are determined by the
wide occurrence of atypical and indistinct forms of this disease, as well as
participation in the epidemic process of three serologically distinct types of
the virus with different characteristics.
At present it is known that not only simians are susceptible to poliomye-
litis but also some species of rodents. Newly born white mice are suitable
experimental animals for work on this disease. Furthermore, data have been ob-
tained on the successful isolation and propagation of the virus in vitro in
tissue culture by the racaod o: rotating test tubes. Particular attention
should be paid to the investigations on active immunization against poliomyelitis
which are carried out under experimental conditions by subcutaneous or the oral
administration of antigen.
The achievements of Soviet investigators in work on virus neuroinfections,
particularly transmissive encephalitides, are widely known. However, it would
be a mistake to assume that all problems in this field have been solved. Further
investigations on the geographic distribution of natural reservoirs of spring-
summer encephalitis and the parasitological and virological characteristics of
these reservoirs are necessary. One must concentrate one's efforts on the in-
vestigation and perfection of the therapeutic and prophylactic methods which
are already available and develaa ne-r Methods for the control of encephalitides.
Although the specific serum,: and vaccine fc,? spring-suer encephalitis were
first sub.tected `c practical tests 1 ,;ears zic, nc improveacnts have been made
since then in the production of these preparations. The production of the
serum can be iaproved b- 'replacing he brain !:utipen (which is currently used
and) which brings about the appearance in the blood of agents that have cytotoxic
properties. Furthermore, the antibcdies contained in the serum can be concen-
trated and purified further. It is necessary to achieve rapid progress in the
practical application of new preparations for the prophylaxis of transmissive
encephalitides by immunization (literally "vacci.nation"J. Among the advances
in this field, one must first of all mention the egg vaccine proposed by A. K.
Shubladze and 0. G. Andzhaparidze. This vaccine has already been tested under
epidemiological conditions and found satisfactory.
The advances made in the field of virology indicate the timeliness of
applying on a practical scale a number of measures for the control of virus
infections.
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One of the most important measures would be organization of the laboratory
diagnosis of virus infections. As a result of scientific research carried out
during recent years, a number of preparations for the diagnosis of virus infec-
tions has been developed and tested on a practical scale. These preparations
include antigens for serological diagnosis and type-specific sera for the de-
tection of the antigen by means of the hemagglutination reaction in the case
of influenza, diagnostic preparations for serological tests in epidemic paro-
titis, and diagnostic preparations for the reaction of complement fixation in
tick encephalitis, Japanese encephalitis, and choriomeningitis.
One might express the hope that the Institute of Virology imeni Ivanovskiy
would develop the production and the release of these preparations for the use
use of sanitary-epidemiological stations. As the preparations are developed
and released, considerable work will become necessary in training virologists
to diagnose virus infections. This work can be successfully carried out by
the institutes of vaccines and sera and the institutes of epidemiology, micro-
biology, and hygiene.
At the present time the industrial production of a number of vaccines and
sera for the prophylaxis of virus infections has been developed. In addition
to antismallpox vaccine, antirabies vaccine, and antimeasles serum, which have
been supplied for many years, the production of gamma globulin, influenza
vac^ine, anti-inf?ucaza serum, vaccines and sera against encephalitis, and
vaccines against pappatcci fever, Omsk hemorrhagic fever, and multiple sclerosis
have been leveloped. It is necessary to expand and improve the production of
these preparations at the institutes of vaccines and sera to an extent which
would result in a supply fully satisfying the needs of therapeutic-prophylactic
institutions. The preparations in question should be made popular among medical
workers. All this will make possible correct planning and organization of the
specific prophylaxis and therapy of virus infections. The problems of the
prophylaxis of virus infections is not solved by the application of immunizing
agents alone, especially since vaccines have not been developed against a num-
ber of virus diseases. However, the scientific knowledge which has been accumu-
lated makes possible improvements in the prophylaxis and control of many virus
infections. For that reason medical workers must be informed of new results
pertaining to the etiology, pathogenesis, immunity, clinical aspects, diagnosis,
therapy, and prophylaxis of virus infections as soon as this knowledge becomes
available and the information should he summarized in the form of instructions,
published articles, booklets, monographs, and handbooks.
Expedient introduction into practical use of scientific achievements in
the field of virology is the most important task of scientific research insti-
tutes. The efficient execution of this task will make possible important ad-
vances in the control of vixas infections.
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