Three main forms of disease linked with CE serocomplex viruses have been proposed: i influenzalike; ii with primary compromise of the bronchiopulmonary system; iii neuroinfectious, which proceeds with a syndrome of serous meningitis and encephalomeningitis. Analysis of the clinical picture of cases examined showed that Eighty-three patients had an influenzalike form of the disease etiologically linked to CE serocomplex viruses.
The incubation period was 7—14 days. The duration of the fever was 4. One of the main symptoms was an intensive headache 3. A survey of patients revealed infection of the sclera Violations of the upper respiratory airways were characterized by hyperemia of the mucous membranes of the fauces With regard to the lungs, Among CNS symptoms, the most common were a decrease in appetite, a stomachache without accurate localization and with liquid stool, and a small increase in the size of the liver with a short-term increase in aminotransferase activity in the blood.
Inflammatory changes in the bronchi—lung system bronchitis and pneumonia occurred as well. In all cases in which it appeared, pneumonia had a focal character with full regression of inflammatory changes through High fever The age of patients with CNS lesions was from 3 to 61 years, with the majority Serous meningitis was observed in 29 patients who arrived at the hospital a mean 3.
The disease began abruptly. The majority Vomiting developed on the first Meningeal signs appeared in The duration of the meningeal signs was 3. The cells of the spinal fluid investigated on the 4.
In Encephalomeningitis caused by INKV was characterized by an abrupt beginning and fast development of focal symptomatology ataxy, horizontal nystagmus, and discoordination against a background of common infectious and meningeal syndromes, including inflammatory changes to the spinal fluid.
The variability of the clinical picture of the diseases caused by CE serocomplex viruses and its similarity—especially at early stages—to that of other infections suggest the necessity of carrying out differential clinical diagnostics with a number of diseases.
The influenzalike form needs to be differentiated, first of all, from influenza, especially in the presence of symptoms of neurotoxicity, as well as from other acute respiratory diseases parainfluenza, adenoviral and respiratory—syncytial diseases , pneumonia including a mycoplasma and chlamydia etiology , and enteroviral diseases.
The main epidemiological features and clinical symptoms that lend themselves to carrying out differential clinical diagnostics for the influenzalike diseases described here are presented in Table 8. Note that considerable difficulties arise in implementing differential clinical diagnostics of the diseases that proceed with acute neuroinfection syndrome serous meningitis, encephalomeningitis , especially when those diseases occur in the same season Table 8.
Winter; Spring; Summer; Autumn. The main criteria in differential clinical diagnostics of the disease etiologically linked with CE serocomplex viruses are as follows see Table 8.
Also observed are insignificant catarrhal phenomena nose congestion, rare dry cough or their complete absence. A radiograph of the chest reveals signs of bronchitis and focal pneumonia with poor clinical symptomatology. An examination of the liver shows that its size, as well as its aminotransferase activity, has increased. Changes in urine, such as albuminuria and, in some cases, cylindruria, are frequently reported.
Finally, symptoms relating to the vegetative nervous system hyperemia of the face and the neck, subconjunctival hemorrhage, bradycardia, and persistent tachycardia can be observed, as can both CNS lesions in the form of serous meningitis and encephalomeningitis in combination with compromise of the bronciopulmonary system, liver, and kidneys. Specific diagnostics of the diseases etiologically linked with CE serocomplex viruses could be based on virological testing using sensitive biological models of newborn mice or cell lines to isolate the strains or on serological testing.
In the presence of the sera taken from patients during the acute period of the disease the first 5—7 days and in 2—3 weeks, the best method of retrospective inspection is a neutralization test. A hemagglutination inhibition test is considerably less sensitive. Both complement-binding reactions and diffuse precipitation in agar have no diagnostic value today. In reference labs, SSHV antigen should be used as well. A quadruple or greater increase in the titers of specific antibodies or the detection of specific antibodies in the second serological test in their absence in the first test are diagnostic criteria.
Supervision of morbidity and of the activity of natural foci linked with CE serocomplex viruses offers the following instructions: i Monitor the patient clinically and the disease epidemiologically. At least six viruses associated with birds have been shown to circulate in the Volga River estuary.
KHURV has not been identified by any serological method, 1 including sera against viruses of the Flaviviridae, Togaviridae, Bunyaviridae, and Orthomyxoviridae families. The genome of KHURV was sequenced, and phylogenetic analysis revealed that it is a new representative of the Orthobunyavirus genus Figure 8. Phylogenetic tree for nucleocapsid protein S-segment of the viruses belonging to the Orthobunyavirus genus.
Phylogenetic tree for RdRp-protein L-segment of the viruses belonging to the Orthobunyavirus genus. The C-part approx. This protein is considered to be a factor in the pathogenicity of the orthibunyaviruses to vertebrates, because it has the ability to block the action of the interferon pathway. More than 20, Aedes , Culex , and Anopheles mosquitoes were examined during the survival period for arboviruses in this region, and no KHURV isolations were obtained.
Nine strains of the virus were isolated from coots Fulica atra. One hundred seventeen birds were examined and were found to have an infection rate of 8.
One strain was isolated from the pygmy cormorant Phalacrocorax pygmaeus. Two hundred eighty-nine cormorants, mostly Ph.
The Phlebovirus genus comprises about 70 viruses that are divided into two main groups based on their ecological, antigenic, and genomic properties: mosquito-borne viruses and tick-borne viruses. The genome of the phleboviruses consists of three segments of ssRNA with negative polarity: L about 6, nt , M about 3,—4, nt , and S about 1, nt Figure 8.
In general, the structure of the genome is the same for mosquito-borne and tick-borne phleboviruses, but the M-segment is shorter in tick-borne viruses and it does not encode the nonstructural protein NSm. The tick-borne phleboviruses comprise viruses of the Uukuniemi group, the Bhanja group, and the two novel related viruses severe fever with thrombocytopenia syndrome virus SFTSV and Heartland virus HRTV , which form separate clusters and are unassigned to any group Figure 8.
The UUKV serogroup currently comprises 15 viruses, but the status of some of them may be revised with the accumulation of more genomic and serological data. Phylogenetic analysis of S-segment of viruses belonging to the Phlebovirus genus. Phylogenetic analysis of M-segment of viruses belonging to the Phlebovirus genus.
Phylogenetic analysis of L-segment of viruses belonging to the Phlebovirus genus. Bhanja virus BHAV was originally isolated from Haemaphysalis intermedia ticks that were collected from a paralyzed goat in the town of Bhanjanagar in the Ganjam district in the state of Odisha, India, in and was assigned to the unclassified bunyaviruses.
These viruses have been merged into the Bhanja group on the basis of their serological cross-reactions. Viruses of the BHAV group are not antigenically related to any of the other bunyaviruses, but they were assigned to the Phlebovirus genus on the basis of a genetic analysis of their full-length genome sequences.
The structure of the RdRp of the viruses with a negative genome includes three main domains. Substitutions in this site are also found in Gouleako virus, an unclassified bunyavirus. Alignment of the partial aa sequence of motif A of RdRp of certain phleboviruses. Conservative dipeptide KW is in frame. Like the M-segments of other tick-borne phleboviruses, that of BHAV has no NSm proteins that are common to mosquitoes-borne phleboviruses.
Phylogenetic analysis has shown that the Bhanja group forms a new separate lineage in the Phlebovirus genus Figure 8. The ungulates, including domestic cows, sheep, and goats, are apparently involved in the circulation of BHAV. Experimental infection of rhesus monkeys by BHAV induced encephalitis. Antibodies have been detected in dogs, roe deer Capreolus capreolus , and wild boars Sus scrofa.
Regardless of their geographical distribution, GSRV and GAV occupy a narrow ecological niche associated with ticks Argas reflexus and birds most likely, pigeons Columbidae. The A. Worse, at night the ticks can go down to the living space and bite people if the dovecote is built into a house. The main vertebrates involved in the circulation of GSRV are apparently birds, particularly the Columbidae. In laboratory experiments, GSRV was isolated from the blood of small doves Streptopelia senegalensis 5, 9, 22, and 30 days after infection.
The virus titer in the blood was 1. In a complement-fixation test, KHAV did not react with serum used in the identification of certain bunyaviruses, so it was categorized in with the unclassified bunyaviruses. A full-length pairwise comparison of L-segments revealed a On phylogenetic trees constructed on the basis of the alignment of full-length genome segments, KHAV forms a distinct branch external to the Uukuniemi group viruses Figure 8. At least 14 viruses with unsettled taxonomy are included in the Uukuniemi group.
Only a single isolation of KHAV was ever obtained, and the ecology of the virus has not been studied. The principal vertebrate host of KHAV is unknown. KHAV was isolated from ticks collected on deer.
The sandfly fever virus group includes Naples and Sicilian subtypes. Sabin gave a clinical description of the disease and demonstrated that immunity developed to one type of virus does not protect from infection caused by the other type.
To date, viruses related to TOSV have been found in all regions of the world, including the Palearctic, Neotropical, Ethiopian, and Oriental zoogeographical regions. Both the Naples and Sicilian strains were isolated from the blood of patients with febrile illness in the vicinity of Aurangabad, Maharashtra state, in northern India. Sandfly virus fever also circulates in western India, as well as in Pakistan.
A case of disease associated with TOSV befell a tourist returning from Elba to Switzerland in , and another struck an American tourist returning from Sicily the same year. Periodic outbreaks of sandfly fever occurred in the first half of the twentieth century in some central Asian republics, Transcaucasia, Moldova, and Ukraine. The viruses can be transmitted by the transovarial route and therefore may not require amplification in wild vertebrate hosts.
Sandflies are peridomestic; the immature stages feed on organic matter in soil and do not require water, but are sensitive to desiccation and therefore are often found in association with humid rodent burrows.
The main vertebrates involved in the circulation of SFNV are rodents, particularly the great gerbil Rhombomys opimus and the long-clawed ground squirrel Spermophilopsis leptodactylus , as well as a hedgehog Erinaceus auritus.
The great gerbil is distributed over areas ranging from near the Caspian Sea to the arid plains and deserts of central Asia. The habitats of Rh. TOSV was isolated from the brain of the bat Pipistrellus kuhlii. Animal and Human Pathology.
Sandfly virus fever does not cause disease in domestic or wild animals. The hosts of Phlebotomus sandflies are usually rodents, which may develop antibodies. Over human experimental volunteers were infected at the time of World War II. The incubation period is between 2 and 6 days, and the onset of fever and headache in those patients was sudden.
Nausea, anorexia, vomiting, photophobia, pain in the eyes, and backache were common and were followed by a period of convalescence with weakness, sometimes diarrhea, and usually leucopenia. Viremia was present 24 h before and 24 h after the onset of fever. Human disease frequently goes unrecognized by local health-care workers.
Studies of antibodies in people indicate that the most infections occur in children. When large numbers of unimmunized adults are introduced into an endemic area, the incidence of disease can be high. Human exposure to sandflies can be reduced by repellents, air-conditioning, and screens on windows.
UUKV was originally isolated from Ixodes ricinus ticks collected in from cows in southeastern Finland. Three strains were isolated from I. UUKV was also isolated from the mosquitoes Ae. UUKV was isolated as well from birds and I. In accordance with the results of electron microscopy, ZTV was assigned to the Bunyaviridae family. Complement-fixation testing revealed that ZTV is most closely related to UUKV, but the two viruses are easily distinguishable in a neutralization test.
More than 60 strains of ZTV were isolated from I. Two strains of ZTV were isolated from I. The viruses of the Phlebovirus genus can be divided into two main ecological groups: those transmitted by bloodsucking mosquitoes subfamily Culicinae and midges subfamily Phlebotominae , together called mosquito borne, and those transmitted by ticks tick borne.
UUKV is a prototypical virus of the Uukuniemi antigenic group, which includes at least 15 related tick-borne phleboviruses Figure 8. The M-segment of UUKV, and indeed, that of all tick-borne phleboviruses, is shorter than the M-segment of mosquito-borne phleboviruses, owing to the absence of the nonstructural protein NSm, which is common in the mosquito-borne phleboviruses. The infection rates of nymphs and larvae of I.
Probably, ZTV has a more pronounced ability to replicate in mosquitoes that are active in the subarctic climate zone tundra landscapes in July through the first half of August at temperatures sufficient for the accumulation of virus in the salivary glands. During this period, circumpolar species predominate: Aedes communis , Ae. The origin of this group of species is said to be southeast Asia. Currently, I. Apparently, ruminants could be infected by mosquitoes or by eating fallen birds.
In central and eastern Europe, a number of vertebrate hosts are involved in the circulation of UUKV: forest rodents Myodes glareolus , Apodemus flavicollis and terrestrial passerine birds—the blackbird Turdus merula , pale trush T.
Viremia and long-term persistence of the virus were demonstrated in experimentally infected birds of many species. Specific antibodies were detected in cows and reptiles. An association was revealed between UUKV and different forms of disease, including neuropathy. A serological survey of 1, people in Lithuania concluded that antibodies existed in 1.
UUKV group viruses, in general, do not play a role in human infectious pathology, although serological studies have detected antibodies to various viruses of this group in people. The genome is represented by ssRNA 9,—12, nt with positive polarity.
The Flavivirus genus includes more than 70 viruses classified into 15 antigenic groups. The Flavivirus virion is spherical 50 nm and consists of a nucleocapsid 30 nm and a lipid bilayer envelope covering it. The lipid envelope contains two transmembrane glycoproteins: M matrix protein, 8 kD and E envelope protein, 50 kD.
Mature viral proteins are produced during a complex process of proteolytic cleavage of the polyprotein precursor by cellular and viral proteases. Most of the flaviviruses are arboviruses; that is, they can be transmitted to vertebrate hosts by bloodsucking arthropod vectors Figure 8. The arthropod vectors of some flaviviruses are unknown.
There is also a group of flaviviruses that infect only insects and not vertebrates. Some flaviviruses e. Flaviviruses are distributed over all continents, with mosquito-borne viruses found mainly in regions with an equatorial and tropical climate And tick-borne viruses found mostly in regions with a temperate climate zone. Flaviviruses belongs to natural foci zoonoses. Phylogenetic analysis of viruses belonging to the Flavivirus genus, based on full-length genome comparison.
The disease arose in the spring—summer in the northern forest—steppe landscape zone in the region around Omsk, western Siberia; Figure 8. In the spring—summer of , the endemic territory enlarged and the number of cases increased to , with 4 lethal outcomes.
In , a large expedition about 50 members under the leadership of Mikhail Chumakov Figure 2. OHFV belongs to the phylogenetic branch of the mammalian tick-borne virus group Figure 8. The OHFV genome has a length of 10, nt, and its organization is common to the flaviviruses. Only six nucleotide substitutions, which encode four amino acids, have been found in the entire genome. Three of four amino acid changes were located in the envelope glycoprotein E. Phylogenetic analysis based on a comparison of partial sequences of the E gene available in GenBank showed that OHFV isolates can be divided to three genetic lineages Figure 8.
The genetic diversity among strains of different lineage is up to The natural foci of OHFV are found in the forest—steppe landscape zone of western Siberia, an area with numerous bogs and a wide network of lakes within the Omsk, Novosibirsk, Kurgan, and Tyumen regions Figure 8.
The infection rate of D. The main host for preimago phases of D. In —, when the number of Microtus gregalis voles fell significantly, there was a concomitant decrease in the number of D. Small animals living in those meadows become infected as they feed on the D. In damp locales, I. Also, D. Their involvement is confirmed by the identity of isolated strains with those isolated from muskrats and sick humans. Experiments with experimentally and spontaneously OHFV-infected Gamasidae ticks testify to the ability of longitudinal more than six months virus preservation.
The principal vertebrate host of OHFV, which is able to directly infect humans, is the muskrat Ondatra zibethicus. This species was introduced into western Siberia from Canada in Their population density reached a modern-day high in the s. Close interactions among O.
Muskrats suffered these epizootics together with other local species of rodents: Microtus oeconomus , M. OHFV was detected in birds and in mosquitoes, but the role of these two animals in virus circulation is not clear. OHFV is transmitted both by Ixodidae tick bites and as the result of direct contact with infected muskrats, their flesh, and fresh fells. OHF morbidity during — reached 1. Then there was a gradual decrease down to single cases. Most OHF cases The northern forest—steppe landscape zone is the youngest landscape of western Siberia, having evolved in place of the former southern taiga landscape zone.
In the south of western Siberia, the following territorial zones can be marked out: i the preferred territory of Tick-borne encephalitis virus TBEV the southern taiga ; ii intermediate territory the boundary of the southern taiga with the northern forest—steppe ; iii the preferred territory of OHFV the northern and southern forest—steppe ; and iv the territory of sporadic cases of OHF part of the southern forest—steppe and steppe.
The seasonal incidence of OHF distinctly correlates with the activity of the principal Ixodidae tick vectors. Cases a few of OHF acquired by direct contact with muskrats occur mainly during the season in which the animals are hunted, in October—January.
In the spring—summer season, OHF cases occur chiefly in rural areas. The age of patients ranges from 5 to 70 years, but cases occur mainly among middle-aged persons 40—50 years old. It appears that all patients infected directly from muskrats develop symptomatic illness. In the last decade of the twentieth century, an increase in OHF natural foci activity took place in the Tyumen , Omsk , — , Novosibirsk —; regular epidemic activity took place on the territory of only four administrative districts , and Kurgan regions.
In the absolute majority of laboratory-confirmed cases, the nontransmissive pathway direct contact with muskrats of the infection dominated. Pathogenesis is determined first of all by the destruction of capillaries, the vegetative nervous system, and the adrenal glands.
The incubation period of OHFV is 2—4 days long. The disease begins abruptly, with fever, head and muscular pain, hyperemia, and injection in the sclera. From the first days of the illness, there are diapedetic bleedings, especially in the nose. Recovery is usually complete, without any residual phenomena; lethal outcomes are possible, but are rare.
OHFV survives up to 20 days in lake water. Water can be contaminated by urine and feces of the infected muskrats or some other rodents. The water pathway in human infection has been discussed in the literature. Prevention of the infection depends on the use of protective respirators and rubber gloves in processing muskrat pelts and on personal protective measures against tick bites.
Cases of laboratory-acquired OHF have been reported in unvaccinated persons, and TBE vaccine is recommended for laboratory personnel working with either virus. Interferon and its inductors have shown a high efficiency in preventing OHF in experiments using animal models.
McLean and W. Donohue in September from the brain of a five-year-old child who was admitted to the hospital with blinking, tremors, and dizziness in the small town of Powassan in the north of Ontario, Canada. Subsequent virological and serological surveys carried out in the Powassan—North Bay and Manitoulin Island areas of northern Ontario during — elucidated a summer transmission cycle involving Ixodidae ticks and small wild mammals.
The genome of POWV is a about 10, nt in length. In North America, POWV was isolated from wild mammals: the woodchuck Mormota monax , the main reservoir , American red squirrel Tamiasciurus hudsonicus , deer mouse Peromiscus maniculatus , red fox Vulpes fulva , eastern gray squirrel Sciurus carolinensis , North American porcupine Erethizon dorsatum , striped skunk Mephitis mephitis , raccoon Procyon lotor , long-tailed weasel Mustela frenata , and gray fox Urocyon cinereoargenteus.
Infection of wild vertebrates most often is inapparent. Nevertheless, human infection rarely develops. Autopsy has revealed widespread perivascular and focal parenchymatous infiltration. In —, the Russian military medical doctor—neuropathologist A. Panov, together with his colleagues A. Shapoval and D. Krasnov, described a neuroinfection with a high level of mortality in the Far East. In that period, the main vector of TBEV— Ixodes persulcatus ticks—was established, epidemiological peculiarities of TBE were studied, and the first anti-TBEV vaccine was developed on the basis of intracerebrally infected mouse brain and was successfully used in medical practice.
Zilber Figure 2. Chumakov Figure 2. Smorodintsev Figure 2. Levkovich Figure 2. Sheboldaeva, and A. Shubladze Figure 2. Soloviev Figure 2. Ryzhkov , parasitologists Ye. Pavlovsky Figure 2. Gutsevich, B. Pomerantsev, A. Monchadsky, and A. Skrynnik , and clinicians A. Panov, A. Shapoval, and Z. Phylogenetic analysis of the complete genome nucleotide sequences of certain strains of TBEV family Flaviviridae, genus Flavivirus.
Specific antibodies to AAV were found among ground squirrels Citellus fulvus , agricultural animals, and humans. Recent genetic studies of TBEV revealed two additional genotypes of this virus on the territory of eastern Siberia Irkutsk Region : for the first one, only a single strain is known today; for the latter, there are five strains in Mongolia.
Korenberg Table 8. Sweden, Slovakia, 6. Bulgaria, 35 Hungary, Poland, Croatia, 40 Latvia, 41 Lithuania, 42 Estonia, Denmark, 31 Germany, Austria, 49 Slovenia, 50 France, 51 Italy, Japan Hokkaido , 55 North and South Korea, China, 58 Mongolia, 59 Kazakhstan, 13 and Kyrgyzstan. The infection rate in I. Occasional vectors are I.
Haemaphysalis inermis , Haem. In the Korea Peninsula, where both I. The northern boundary of I. The most suitable climatic conditions for these ticks are within the south taiga. Imago tick activity begins in the third d decade of April and reaches a maximum in the second and third decades of May or in the first and second decades of June, with activity beginning to decrease in the third decade of June.
This time frame correlates with morbidity dynamics having an 8- to day lag Figure 8. Trends in the incidence of TBE in Russia, by month as a percentage of the amount of disease for the year, according to long-term data. The ecological links of TBEV during its circulation in natural foci are extremely diverse as the result of wide distribution of this virus Figure 8.
Ixodidae ticks, mainly I. Ticks become infected as they suck blood from a vertebrate host with a level of viremia that is equal to or higher than the threshold required for infection. Ticks can also become infected from an uninfected vertebrate host as they suck blood together with infected ticks. Transovarial and transphase transmission of TBEV has been described in the literature; nevertheless, the effectiveness of vertical transmission of TBEV is low.
Infected ticks have been found on the clothing of humans at a fequency 5—20 times higher than uninfected ticks have been found. A preliminary investigation 82 concluded that this strain belonged to Negishi NEGV virus, 85 and later the possibility was discussed that the strain belonged to a separate, Malyshevo virus.
TBEV has been isolated many times fromticks and fleas of the superfamily Gamasoidea living in nests of rodents and birds Table 8. Hosts for the preimago stage of Ixodidae ticks—Asian chipmunks Tamias sibiricus , shrews members of the Soricidae family , bank voles Myodes glareolus , field voles Microtus agrestis , mountain hares Lepus timidus , and 74 species of birds Table 8.
Persistent TBEV infection in bank voles and field voles has been found during the winter period. Infection among vertebrates occurs mainly by tick bites. In rare instances, alimentary transmission of TBEV through milk containing viruses is possible.
There are two basic modes of human infection by TBEV: i as the result of being bitten by infected Ixodidae ticks the main mode ; and ii as the result of consuming infected raw goat, sheep, and cow meat, milk, or dairy products mainly in natural foci linked to Ixodes ricinus. The latter pathway of TBEV distribution often involves whole families.
Many laboratory infection cases usually by aerosol have been described. Several hundred cases are recorded in Europe Table 8. In neighboring Austria, where the vaccination rate is higher, the index is lower 0. The risk of infection depends upon the frequency of tick bites, which is different for populations living in the different landscape belts.
A mathematical model for evaluating the infection rate and the probability of developing the disease as a function of the density of the tick population, its infection rate and biting activity, and the level of the immune human layer was developed by D. Lvov and coauthors. The same approach, which is also suitable for other arboviral infections, was used for landscape-epidemiological zoning of TBEV natural foci in Altai Krai in the southern part of western Siberia: More than 10, residents living in the different landscape belts on a territory about , km 2 were tested by serological methods Figure 8.
The tests produced a good fit between calculated and registered morbidity data Table 8. Designations for epidemiological regions in respect to the level of immune layer: 1. TBE can be realized in several pathogenetic variants. An inapparent clinical form is characterized by short-term localization of TBEV in lymph nodes and immune cells, as well as by extranervous reproduction without viremia.
Infection is terminated by the development of stable immunity. The incubation period ranges from 1 to 30 days, but usually is 7—12 days. The onset of illness in typical cases is abrupt and with a headache. Malaise, vomiting, general hyperesthesia, and photophobia develop. Clinical symptoms of TBE, as well as the severity of the disease, are at least partially determined by biological properties of the virus.
Human disease of the first type is usually clinically more severe in the acute phase, but is associated with a lower rate of chronic CNS sequelae. The first phase starts with sudden fever, flulike symptoms pronounced headache, weakness, nausea, myalgia, arthralgia , and conjunctivitis. Convalescence is prolonged, and neurological and psychotic sequelae often include paresis and atrophic paralysis of the neck and shoulders. Many authors have noted a decreasing number of severe TBE cases.
Specific and nonspecific prophylaxis tools are highly efficient if they are utilized correctly. Personal safety includes protection against ticks. Vaccination against TBEV has a long history of success. Mass vaccination of populations in the endemic territory is necessary. Single cases of TBEV among vaccinated persons need to be investigated because possible causes are personal peculiarities of the immune system and errors in the control of vaccine production.
This danger was eliminated after vaccines were developed which used TBEV strains that reproduced in cell cultures. Levkovich and G. Zasukhina, and their high efficiency was demonstrated during — in controlled epidemiological trials carried out by D.
Lvov in Kemerovo Region, western Siberia Figure 2. The total number of people tested was 1,, Etiotropic treatment includes three groups of antivirals: i serological specific anti-TBEV immunoglobulin, immune blood plasma ; ii enzymes ribonuclease ; and iii interferon.
Japanese encephalitis virus JEV was originally isolated by H. Hayashi in from a patient who died with encephalitis and then, again, in from a patient who died with a fever in Tokyo. American military personnel massed on Okinawa and preparing to invade Japan were demoralized by an outbreak of encephalitis among the indigenous people. Phylogenetic studies indicated that JEV isolates be divided into five genotypes, the distributions of which overlapped Figure 8.
Genetic diversity between strains of the different genotypes ranges from 9. JEV circulation in the equatorial and subequatorial climatic zones is year-round and is seasonal in the tropical, subtropical, and temperate belts, with a peak at the end of summer and the beginning of fall.
JEV is brought from the equatorial and tropical climatic belts to the subtropical and temperate belt during the spring migration of birds. About 30 species of mosquitoes are able to transmit JEV; nevertheless, only some of them are effective vectors.
Additional vectors are Cx. The JEV contamination index reaches among Cx. Upon entrance into the host cell, the plus-strand RNAs generated by the polymerase are used as mRNA for protein production. Instead, the virus uses its reverse transcriptase to synthesize a piece of ssDNA complementary to the viral genome. This allows the virus to insert its genome, in a dsDNA form, into the host chromosome, forming a provirus.
Unlike a prophage, a provirus can remain latent indefinitely or cause the expression of viral genes, leading to the production of new viruses. Excision of the provirus does not occur for gene expression. Viroids are small, circular ssRNA molecules that lack protein. These infectious molecules are associated with a number of plant diseases.
Since ssRNA is highly susceptible to enzymatic degradation, the viroid RNA has extensive complementary base pairing, causing the viroid to take on a hairpin configuration that is resistant to enzymes. Prions are infectious agents that completely lack nucleic acid of any kind, being made entirely of protein.
They are associated with a variety of diseases, primarily in animals, although a prion has been found that infects yeast! The prion protein is found in the neurons of healthy animals PrPC or Prion Protein Cellular , with a particular secondary structure. Accumulation of the pathogenic form causes destruction of brain and nervous tissue, leading to disease symptoms such as memory loss, lack of coordination, and eventually death. Skip to content Viral Classification Since viruses lack ribosomes and thus rRNA , they cannot be classified within the Three Domain Classification scheme with cellular organisms.
Study Questions What is the Baltimore system of classification? What viral characteristics does it use? How does each viral group make proteins and replicate their genome? Where do the necessary components come from?
What strategy do dsDNA viruses use for control of gene expression? What are concatemers? What are productive and latent infections? What is a replicative form? What is rolling circle replication? What is the advantage of these viral mechanisms? What is a pregenome? Thus these two strategies are closely related. Some ambisense viruses package copy genomes that can be used as templates for transcription, such that the full complement of viral genes can be transcribed soon after infection.
It should be noted that packaged copy genomes are not mRNAs and are not translated. Reoviruses also have segmented genomes, packaging 11—12 segments of dsRNA. Reoviruses are nonenveloped and particles consist of two or three concentric icosahedral capsid layers.
A unique feature of the reovirus replication cycle is that the genome segments are transcribed from within the capsid. The genomes of RNA viruses have some common general features. Obviously there are one or more open reading frames that encode the viral proteins. But there are also regions of RNA that do not code for protein. These non-coding regions NCRs or untranslated regions UTRs are often highly conserved within a virus family, indicating that they have important functions.
NCRs may have specific, critical nucleotide sequences but in some cases they are regions of the genome that fold into conserved structures, and structure may be more critical than a specific sequence.
Of course a source of RdRp must be supplied. RdRp may be encoded in the minigenome or may be supplied in trans by using a cell line stably expressing the viral RdRp, for example.
The sequences required to direct RNA replication are often fairly simple and can be linked to virtually any RNA sequence to drive its replication. These promoter sequences can be rather short but provide a means to direct the RdRp to internal sites on the genome.
There may also be specific RNA sequences that signal polyadenylation. There are a variety of different strategies that RNA viruses use to regulate transcription and genome replication, but all involve RNA sequences found in the genome. The RNA genomes of some viruses are highly structured and extensively base paired. The IRES serves as a platform for ribosome assembly. Promoters can be quite long and complex and promoter regions themselves are not transcribed.
It is particularly important, in the case of genome synthesis, that genetic information not be lost or modified; however, mRNAs are often capped and polyadenylated. Are the methods for priming viral mRNA synthesis the same or different from the methods of priming genome replication?
The RNA viruses seem to have experimented widely. For example, the picornaviruses use poly A tracts encoded in the genome. Among the negative-strand RNA viruses, those in the order Mononegavirales use a stuttering mechanism to synthesize long poly A tracts from short poly U tracts Fig. A strategy to regulate mRNA synthesis. This figure shows the organization of a paramyxovirus genome paramyxoviruses are members of the order Mononegavirales ; negative-strand RNA viruses with unsegmented genomes.
Each protein-coding region is flanked by regulatory sequences that control capping and polyadenylation. The order of the genes on the genome regulates the relative quantities of mRNAs synthesized.
Because RdRp does often dissociate from the genome during transcription, the downstream genes are produced in lower quantities. Even with fairly simple genomes, RNA viruses must, and do, regulate the amounts of genome, copy genome, and mRNAs that are synthesized during an infection. It is much more efficient to synthesize many genomes from each copy genome. Internal promoters for mRNA synthesis can vary in sequence, controlling the relative affinity of the transcription complex for each mRNA.
An important feature of RNA viruses is that many exist in nature as quasispecies. The term quasispecies is used to describe a group of closely related, but nonidentical genomes Fig. A Positive-strand RNA viruses exist as quasispecies, complex mixtures of related genomes. The mixture is more fit than any individual genome; fitness is maintained by generation of new variants in response to selective pressures. B Potential for safer vaccines.
If the fidelity of RdRp is increased the population remains more homogeneous. Therefore an attenuated virus with a high-fidelity RdRp is more likely to remain attenuated. Poliovirus PV is a good example of a virus that forms a quasispecies.
If one examines genome sequences from a mouse experimentally infected with PV serotype 1, we find that the genomes are not identical, although they are all clearly related to one another. To the surprise of many virologists, it turns out that the population quasispecies may be more fit than any individual genome.
Or put another way, we cannot find any single genome in the population that replicates better than the group as a whole and in fact, most individual genomes replicate more poorly than the group. Why this occurs is not always clear, but an animal is a very complex ecosystem. Different members of the quasispecies may be better adapted to different niches in the animal. How does a quasispecies form? But as the cloned virus replicates, mutations accumulate generating a quasispecies.
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