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Pathogenicity of feline leukemia virus is commonly associated with variant viruses.

Many of the serious diseases resulting from feline leukemia virus (FeLV) infection are associated with the generation of novel variant viruses. The prototype FeLV-A virus is highly stable and circulates in the cat population without apparent antigenic change. However, recombination with cellular oncogenes produces viruses which cause leukemia or other malignant diseases. Other recombinants within the env genes of FeLV-A and endogenous FeLV are recognized as belonging to a second subgroup, FeLV-B, the presence of which is correlated with an increased risk of infection with FeLV and a higher incidence of leukemia. Mutants of FeLV which affect the env gene are phenotypically of a third subgroup, FeLV-C, and have a close association with erythroid aplasia. None of these viruses, apart from FeLV-B, is transmitted further in nature. Therefore the generation of these novel viruses and the production of disease is an inadvertent consequence of FeLV infection.

Anemia

Genetic mechanisms of antigenic variation in infectious bursal disease virus: analysis of a naturally occurring variant virus.

The major immunogenic protein VP2 from a pathogenic field isolate (variant A virus) of infectious bursal disease virus (IBDV) was cloned and sequenced to examine antigenic variations. The VP2 open reading frame consists of 1509 nucleotides and codes for a 503 amino acid protein. Overall, the VP2 amino acid sequence of the variant A virus shares 98.6% identity with VP2 genes from other published IBDV strains. However, within the central region of VP2 (amino acids 222-334) lies a highly divergent area that we have termed the variable domain. Relative to five other IBDV isolates, a total of six amino acid changes occur within the variable domain of the variant A virus. At positions 284-288, a substitution of isoleucine to threonine, a decrease in the number of Chou and Fasman beta turns, and a switch from a hydrophilic to a hydrophobic region are found only in the variant A virus. Together these changes predict a decrease in antigenicity as determined by calculation of potential antigenic sites. This suggests that only minor changes within VP2 contributed to the emergence of a variant virus that can cause disease in immunized birds.

Amino Acid Sequence

Role of virus variants and cells in maintenance of persistent infection by measles virus.

Hamster embryo fibroblasts persistently infected with a derivative of the Schwarz vaccine strain of measles virus spontaneously released virus particles with an average buoyant density considerably lower than that of the parental virus. The released virus contained all of the measles virus structural proteins and interfered with replication of standard virus. All of the virus structural proteins were associated with a membrane-free cytoplasmic extract from the persistently infected cells. Membrane-free cytoplasmic extracts prepared from Vero cells lytically infected with Schwarz strain measles contained little or no virus envelope structural protein. Maintenance of persistent infection may involve both the presence of virus variants and a defect in the ability of the infected cell to replicate the virus efficiently.

Animals

Characterization of a Sinbis virus variant with altered host range.

A variant of Sindbis virus which is much more infectious for mouse cells than the standard virus has been examined for biochemical properties which might be responsible for this biological difference. The variant has a much enhanced ability to adsorb to mouse plasmacytoma (MOPC 315) cells, but when these cells were pretreated with heparin, they were able to adsorb the standard virus almost as well as the variant. This suggested that there was a surface charge difference between variant and standard virus. Differential elution of the viruses from hydroxyapatite and the results of isoelectric focusing of the virion glycoproteins substantiate this interpretation. Both viral glycoproteins E1 and E2 from the variant were more negatively charged than those of the standard virus but we were unable to find changes in tryptic peptides of the variant. Differences were found in stability of the two virus strains to heat and proteolytic enzymes.

Adsorption

[Biological properties of tick-borne encephalitis virus variants isolated by transfection].

Variants of tick-borne encephalitis virus (TBA) isolated by inoculation of pig embryo kidney cell cultures (SPEV) with infectious DNA from chronically infected HEp-2-Soph cells produced cytopathic effect in SPEV cell cultures. In suckling mice inoculated intracerebrally they induced inapparent infection. Titers of TBE virus variants in SPEV cell cultures treated with DEAE-dextran increased considerably. As a result of filtration a variant was obtained replicating in SPEV cell cultures without any CPE. The cytopathic effect developed only when SPEV cells were treated with DEAE dextran. This variant is assumed to consist of two subpopulations 1 of which produces the cytopathic effect in DEAE-dextran-untreated SPEV cells while the other needs DEAE-dextran treatment of cells for its CPE manifestation.

Animals

Encephalomyocarditis (EMC) virus-induced myocarditis by different virus variants and mouse strains.

The mode of occurrence of encephalomyocarditis (EMC) virus-induced myocarditis in mice was pathologically and virologically investigated using 2 virus variants (highly diabetogenic EMC-D and non-diabetogenic EMC-B) and 2 mouse strains (diabetes-susceptible BALB/c and diabetes-resistant C57BL/6). Mice were inoculated with 10(5) PFU/head of the virus intraperitoneally and observed up to 7 days post inoculation (7DPI). As compared with EMC-B-infected BALB/c and EMC-D-infected C57BL/6 mice, EMC-D-infected BALB/c mice developed marked myocarditis and exhibited a heart virus titer of more than 100 times above that of the others after 4DPI. Electron microscopically, small aggregations of virus-like particles, with 20-25 nm in diameter, were found in the cytoplasm of degenerated cardiomyocytes showing mitochondrial and myofibrillar degeneration in EMC-D-infected BALB/c mice.

Animals

Characterization of two Chikungunya virus variants.

The stability of virulence and plaque size of two variants of Chikungunya virus (genus Alphavirus) were examined. Mouse pathogenicity did not coincide with infective virus levels in the brain. An increase in the average survival times of mice receiving a lethal dose of the variant which allowed prolonged survival at high doses and harvested late after infection was observed. Studies in Vero cells suggested that the number of infective virus particles produced per cell was lower with the small plaque variant, though these cells were selective for this clone. On the other hand suckling mice or antisera favoured a more virulent large plaque variant.

Animals

Isolation of a Sindbis virus variant by passage on mouse plasmacytoma cells.

A variant of Sindbis virus has been isolated by growing a stock of virus, previously passaged on chicken embryo cells, in mouse plasmacytoma (MOPC 315) cells in suspension culture. An indirect immunofluorescence test and infective center assay showed that only a small fraction of cells could be infected by the stock wild-type virus, but that the population of virus accumulating after a few passages on the mouse cells had host-range properties distinct from the stock virus. The mouse-passaged virus retained its virulence for the original host and back-passaging of this virus on chicken cells did not change its newly acquired properties. Thus, this variant appears to be a genetically distinct form of Sindbis that adsorbs to and grows much better than the stock virus on several types of mouse cells including cultures of mouse macrophages.

Animals

Studies on a measles virus variant inducing persistent infections in cultured cells.I. Isolation and characterization of plaque purified virus clones.

Attempts were made to characterized by a plaque assay two variants of the Edmonston strain of measles virus and to obtain plaque purified virus populations. The UP non-cytocidal variant, in all the examined cell systems, mainly produced small but also large plaques; the DP cytocidal variant always large plaques. Three clones, UP-SP4, UP-LP4 and DP-LP4, were derived by plaque purfication respectively of the UP small plaque, UP large plaque and DP large plaque forming particles. The virus populations of the clones could be distinguished by some other biological and physical characters: cytopathic effect in roller tube cultures, growth potential in HeLa cells, thermal stability at 45 degrees C, stability of the properties during serial passages at different input multiplicity. The hypothesis was supported that the typical properties of the UP and DP variants are host-independent and genetically controlled viral markers.

Animals

Immunologic characteristics in relation to high and low leukemogenic activity of radiation leukemia virus variants. I. Cellular analysis of immunosuppression.

Infection of adult C57BL/6 mice with variants of the radiation leukemia virus resulted in variable leukemia incidence. One variant, designated D-RadLV, induced lymphatic leukemia in 0 to 25% of mice after virus inoculation directly into the thymus of young adult mice. The leukemia incidence could be increased to 80 to 100% by host exposure to x-rays. The second variant, A-RadLV, induced lymphatic leukemia in 80 to 100% of similarly inoculated mice without the need for additional radiation treatment. Adult mice were inoculated with D-radLV or A-RadLV. Both variants reduced the immune response to sheep erythrocytes whereas only D-RadLV had an immunosuppressive effect after immunization with a thymus-independent immunogen polyvinyl-pyrrolidone (PVP). Results of transfer experiments indicated that the immunosuppressive effects were expressed at the immunocompetent cell level. Thymus-derived cells were affected by A-RadLV since their immunocompetent function was impaired, whereas D-RadLV affected the marrow cell population of immunocytes. Exposure of D-RadLV-inoculated mice to x-rays induced functional impairment of both thymus and marrow cells. Since the radiation leukemia virus induces "T" lymphatic leukemia it could be proposed that the initial tropism of the virus to thymocytes would lead to high leukemia induction potential, whereas virus tropism to bone marrow cells would yield a low leukemia incidence. The coleukemogenic effect of x-rays could perhaps be related with its capacity to alter and introduce a change in virus-lymphoid cells interaction.

Animals

[Determination of antibody specificity to a new influenza B virus variant by means of the immunoadsorption test].

Immunoadsorption test was used for determination of the strainspecificity of antibody to a new antigenic variant of influenza B virus (B/Hong Kong/5/72 and B/Yamagata/1/73) in human sera collected in April, 1973--March, 1974. The new strains were shown to be circulating in Moscow City only late in February and in March 1974. The experimental data show the immunoadsorption test to give more definite ideas not only on the qualitative differences between strains but also on the specificity of the immunologic response.

Adsorption

Geographical distribution of swine (Hsw1N1) and Hong Kong (H3N2) influenza virus variants in pigs in Southeast Asia.

Influenza viruses of the Hsw1N1 and H3N2 subtypes were isolated in Hong Kong from pigs originating from Hong Kong, People's Republic of China (PRC), Singapore, and Taiwan. The H3N2 isolates were from pigs from Hong Kong and PRC, whereas the Hsw1N1 isolates were from pigs from Hong Kong, PRC, Singapore and Taiwan. The hemagglutinins of the H3N2 isolates were similar to those of the earlier A/Hong Kong/1/68 and A/Port Chalmers/1/73 variants from man. The Hsw1N1 isolates were similar to the human A/New Jersey/8/76 virus. These studies extend the geographical range of Hsw1N1 influenza virus and suggest that pigs in southeast Asia, like those in North America, harbor Hsw1N1 influenza viruses. These findings underline the importance of pigs as potential reservoirs for future human pandemics by the continued isolation (in Asia) of H3N2 and Hsw1N1 influenza viruses.

Animals

Immunologic characteristics in relation to high and low leukemogenic activity of radiation leukemia virus variants. II. Analysis of the immune response.

Comparative analysis of immune responses induced by two variants of the radiation leukemia virus having high (A-RadLV) or low (D-RadLV) leukemogenic potential was performed. Effective immunization could be induced only with RadLV variants having low leukemogenic potential when injected into adult mice of specific strains, (D-RadLV in C57BL/6 mice and A-RadLV in (BALB/c X C57BL/6)F1 mice). Immunologic cross-reactivity among the RadLV variants and the leukemic cells induced by them was demonstrated in several systems. Transplantation resistance could be induced in certain strains against challenge of leukemic cells induced by both RadLV variants. Isoantisera, raised in the suitable strains, could neutralize effectively the leukemogenic activity of both A-RadLV and D-RadLV. Leukemic cells induced by each of the variants shared cell-surface antigens. Circulating anti-tumor antibodies, induced by both variants in the appropriate strains, lysed efficiently the target leukemic cells.

Animals

Vaccinia virus variants as presumable cause of vaccinial complications.

Two vaccinia viruses isolated from patients with vaccinial complications (vaccinial ulcer, postvaccinial seizures) showed qualitative differences from the original parental strain. After intradermal injection of the viruses into the rabbit marked necroses developed, which the original strains did not produce. While the parental virus did not grow on the chorioallantoic membrane at 41 degrees C after 2 days incubation, the vaccinia variant produced typical lesions at that temperature. Also the yield of infectious virus on various cell systems was 1--2.5 logs higher for the virus than for the original vaccine strain. With the plaque technique differences were seen in the appearance and size of plaques between the variant and the parental vaccinia strain. These results indicate that virus of an increased pathogenicity could be isolated from the patients and this might be causally connected with the postvaccinial complications from which they were suffering.

Animals

[Comparative antigenic characteristics of 2 Marek's disease virus variants and of herpesvirus of turkeys isolated in the USSR].

The antigens induced by pathogenic (55) and nonpathogenic (83) variants of Marek's disease virus, the Kekava strain (MDV-Kekava) and herpesvirus of turkeys, the M-24-72 strain (HVT-M24-72) were tested in the agar gel precipitation test. The antigens were prepared from feather follicles (FF) of the infected chickens, from the infected cultures of chick embryo fibroblasts (CEF) and from the culture fluid (CF) of these culttures. In the FF and CEF cultures infected with MDV-Kekava-83, the synthesis of the antigens was 6-10 times as low as in the FF and CEF cultures infected with MDV-Kekava-55. Both variants of MDV-Kekava retained their capacity for antigen synthesis in the CF up to 84 passages. Three antigens or three groups of antigens were found in the preparations examined: (1) strong common antigens in the CF and FF preparations; (2) weak common antigens in cell preparations and CF; (3) strong antigen(s) in cell preparations not identical to the CF and FF antigens. In CEF culture preparations infected with MDV-M-24-72, using sera from chickens with Marek's disease an antigen was detected partially identical to the weak antigen of cell preparations and cross-reacting with strong antigens of the FF, CF and cell antigens of MDV. No antigen was found in concentrates of CF from the CEF cultures infected with MDV-M-24-72 with the sera used. It is suggested that the CF and FF MDV antigens are virus antigens, while antigens of the cell preparations of this strain are autoantigens or embryonal antigens. Data are presented on relationship between the MDV-Kekava antigens with the MDV-HPRS-16 antigen.

Animals

Granulopoiesis in "preleukemic" mice with anemia induced by Rauscher leukemia virus, variant a.

To understand further the hematopoietic dyscrasias induced by a variant (a) of Rauscher leukemia virus (RLV), we used Escherichia coli endotoxin to stress the hematopoietic system of control and RLV/a-infected BALB/c mice. During the preleukemic stages of virus infection, there was slight splenomegaly without peripheral blood erythroblastosis. Granulocyte release and tissue mobilization mechanisms appeared unaffected by the RLV/a infection. Both RLV/a-infected and control mice reacted to endotoxin with peripheral granulocytosis and peritoneal granulocyte mobilization, though the circulating granulocyte levels in RLV/a-treated mice initially were lower than those in controls. Spleen of RLV/a-infected animals were larger than those of controls, but both responded to endotoxin with elevated numbers of granulocytes and erythroblasts. Since numbers of bone marrow erythroblasts in both groups of mice were decreased after endotoxin, stem cell competition and/or shunting of stem cells from marrow to spleen may have been involved. Endotoxin also induced rapid falls in hematocrit levels in both groups. These studies suggested that RLV/a-infected mice can be a model to study 1) erythropoietic dysfunction uncomplicated by defective granulopoietic release and tissue mobilization control mechanisms, and 2) progression of evolving granulocytic leukemia.

Anemia

Persistence of Hong Kong influenza virus variants in pigs.

The A/Hong Kong/1/68 (H3N2) influenza virus which has not been isolated from man for several years, was recently isolated from pigs in Hong Kong. Influenza viruses similar to A/Victoria/3/75, which are currently circulating in man, were also isolated from pigs. Both above-mentioned viruses could be transmitted readily from pig to pig in experimental studies. The isolation of influenza viruses similar to A/Hong Kong/68 from pigs in 1976 suggests that pigs may serve as a potential reservoir for future human pandemics as well as a possible source of genetic information for recombination between human and porcine strains of influenza virus.

Animals

The isolation of a Bwamba virus variant from man in Western Kenya.

A bwamba group virus was isolated from the blood of a febrile child on the Kano Plain, Kenya. The isolate (NY-45), closely resembling Bwamba, established infection in both Anopheles gambiae and Mansonia uniformis. Neither the Bwamba nor the Pongola prototype strains grew in both species. In gel-diffusion tests NY-45 virus passaged through mosquitoes exhibited a line of identity with Pongola antiserum. In contrast no cross-reaction was observed with NY-45 virus which had not previously been passaged through mosquitoes.

Adult