Is the anti-sarcoma and anti-viral cytokine "plasma factor" a novel chicken Y-box protein?

A line of research beginning in the early 1960s with the observation that West Nile virus and, later, several strains of rabies virus could inhibit the development of the Rous sarcoma virus-induced tumor in the wing-web of chicken (a "sarcoma-blockade") eventually culminated in the characterization of a 14-kDa circulating anti-sarcoma and anti-viral activity christened "plasma factor" (PF) which, unlike the interferons, inhibited the replication of diverse RNA-containing viruses, but not of any DNA-containing viruses. The possibility that this 14 kDa protein represented a novel antiviral cytokine has been strengthened by analysis of partial amino acid sequencing data which suggest that this 14-kDa cytokine may correspond to the 127-amino acid-long chicken YB2-like protein (Locus: XP_423576) deduced very recently from the genomic sequencing of chicken. Biologically, proteins of the Y-box family (such as chicken YB1 and YB2) not only bind DNA and thus regulate transcription but also bind single-stranded RNA in a sequence-specific and reversible manner, repress viral RNA translation, inhibit retroviral transformation of chicken fibroblasts, and are known to regulate transcription of human immunodeficiency virus and hepatitis B virus. Taken together, the available data point to a novel anti-viral cytokine with a novel mechanism of action.

Alloantigen system L affects the outcome of rous sarcomas.

This study was designed to examine the alloantigen system L effects on Rous sarcomas in three B complex genotypes. The parental stock was 50% Modified Wisconsin Line 3 x White Leghorn Line NIU 4 and 50% inbred Line 6.15-5. Pedigree matings of two B(2)B(5) L(1)L(2) sires to five B(2)B(5) L(1)L(2) dams per sire produced experimental chicks segregating for B and L genotypes. Chicks were inoculated with 20 pock-forming units (pfu) of Rous sarcoma virus (RSV) at 6 weeks of age. Tumors were scored six times over 10 weeks postinoculation after which the tumor scores were used to assign a tumor profile index (TPI) to each chicken. Tumor growth over time and TPI were evaluated by repeated-measures analysis of variance and analysis of variance, respectively. Six trials were conducted with a total of 151 chickens. The major histocompatibility (B) complex affected the responses as the B(2)B(2) and B(2)B(5) genotypes had significantly lower tumor growth over time and TPI than the B(5)B(5) genotype. Separate analyses revealed no significant L system effect in B(2)B(2) or B(2)B(5) backgrounds. However, L genotype significantly affected (P < 0.05) both tumor growth over time and TPI in B(5)B(5) chickens. B(5)B(5) L(1)L(2) birds had TPI significantly lower than B(5)B(5) L(1)L(1) chickens but not B(5)B(5) L(2)L(2). Mortality was lower in the B(5)B(5) L(1)L(2) birds than in B(5)B(5) L(2)L(2) chickens. The L system, or one closely linked, affects the growth and ultimate outcome of Rous sarcomas. The response may depend upon the genetic background as well as MHC type.

Cerebral blood flow response to the tissue temperature in tumour and brain tissues.

The response of regional-cerebral blood flow (rCBF) to change in the tissue temperature was studied using normal and tumour-bearing monkeys. The local brain was selectively heated by the external microwave irradiation, while the body was kept hypothermic (30.1 +/- 0.1 degrees C, mean +/- standard error) by immersion in a cold water bath. The rCBF in brain and/or tumour tissues was sequentially measured by inhalation hydrogen clearance method. In the normal animal study (n = 7), rCBF changed in response to the tissue temperatures over a range of 29.4-40.7 degrees C with a constant rate 15.2% per degree Celsius change. Similarly, rCBF in the tumour-bearing animals (n = 7) changed proportionately with change in the tissue temperatures over a range of 28.4-42.5 degrees C in tumour and 27.6-41.8 degrees C in brain tissue. The rate in rCBF change per degree Celsius was 6.5% for tumour, which was significantly smaller than that for brain tissue (13.5%) (P less than 0.01). These results indicated that rCBF can be controlled by the defined application of selective heating with temperatures ranging from shallow hypothermia to modest hyperthermia. Vascular response to temperatures in the tumour and brain tissues may play a significant role in the application of heat to brain tumour treatment.

Causes of mortality in chickens that regressed a Rous sarcoma virus-induced tumor.

Rous sarcomas were induced in 6-week-old chickens of several genetically different stocks: inbred lines C, 6(1), 6(3), and 7(2); crosses of inbred lines (6(3) X 7(2)) F4 and (6(1) X 15(1)) F2 X 6(1); and reciprocal crosses (15(1) X 100) F1 X 15(1) and (15(1) X 100) F1 X 100. The resulting tumors were scored for size six times during a 10-week period. Females that had completely regressed their sarcomas were placed in individual laying cages and examined weekly for reappearance of a tumor. After death, the probable cause was determined by necropsy. The major causes of death in the pooled sample of 49 females were fatty liver hemorrhagic syndrome (24.6%), reproductive disorder (14.2%), Marek's disease (12.2%), and lymphoid leukosis (6.1%). Elapsed time between tumor regression and death from any cause ranged from 21 days to 1930 days (5.3 years). One tumor recurred, this in a bird which eventually died with a massive sarcoma in the left wingweb and Rous metastasis in liver tissue. These data provide evidence of specific resistance to neoplastic disease.

Genetic control of Rous sarcoma regression in inbred lines of chickens.

The fate of tumours induced by PR-RSV-C was investigated in highly inbred chicken lines congenic at the B complex, the major histocompatibility complex of the chicken. The results demonstrated that Rous sarcoma regression in congenic CB and CC lines was controlled by a gene within the B region of the chromosome. Another congenic pair of the WA and WB lines also differed in the ability to regress RSV-induced tumours and a gene within the B complex also appeared to have a significant role in the regression of Rous sarcomas.

[Rous virus-induced sarcoma study of Macaca mulatta monkeys]. / Izuchenie sarkom, indutsurovannykh virusom Rausa, u obez'ian Macaca mulatta.

The Carr-Zilber strain of Rous sarcoma virus is highly oncogenic for adult monkeys of the species Macaca mulata. In the present study the authors examined some characteristics of tumor growth, when the tumor either regressed or progressed until it killed its host. The kinetics of antibody formation to antigens coded as CZ-RSV was followed in animals with a different course of tumor disease. The sera of animals under test contained virus-neutralizing antibodies in addition to gs antibodies.

Behaviour of normal and neoplastic rat cells on grooved substrates.

The distribution and shape of rat cells cultivated on plastic surfaces containing cylindrical areas of various radii and grooves of various depths were studied. Normal embryo cells and two lines of neoplastic cells (LW13K2 and RsK4) were used. The nuclear shape, orientation of the nuclei and migration of cells from the bottom of the grooves were assessed by quantitative methods. All characteristics of the behaviour of both neoplastic cell lines on the grooved substrates were found to be different from those of normal cells: a) the nuclei of neoplastic cells, in contrast to those of the normal ones, did not undergo additional elongation on the cylindrical areas of the substrate; b) the orientation of neoplastic cells with regard to the axis of the cylindrical substrate was decreased or absent; c) the migration of neoplastic cells from certain types of the grooves was decreased. It is suggested that the different reaction to the geometry of the substrate may be a characteristic feature of transformed cells. Possible mechanisms of these alterations are discussed.

RSV-induced tumors in chickens: resistance to pulsed current in terminal and non-terminal types.

Terminal Rous sarcoma virus-induced tumors in chickens had lower resistance to a pulsed current than non-terminal tumors or healthy tissues. This finding suggests the existence of some basic physiological difference between terminal and non-terminal tumors. The terminal tumors may have a higher concentration of mobile ions than either non-terminal types or healthy tissue.

Body temperature and tumor virus infection. I. Tumorogenicity of Rous sarcoma virus for reptiles.

Rous sarcoma virus (RSV) was oncogenic for the following nine species of reptiles representing 6 families from Chelonia and Squamata orders: family of Testudinidae: 1. Testudo horsfieldi, family Agamidae: 2. Agama sanguinolenta; 3. Agama erythrogastra, family Lacertidae: 4. Eremias persica; 5. Eremias velox; 6. Eremias grammica, family Scincidae: 7. Eumeces taeniolatus, family Boidea: 8. Erix tataricus, 9. Ancistrodom blomhoffi. RSV did not induce tumors in 13 studied species of reptiles. Histologically 26 reptile tumors studied were polymorphous sarcomas with spindle-shaped (fibroblast-like), round and polygonal macrophage-like cells and sometimes peculiar giant polynuclear cells. Chromosomal analysis showed that reptile tumors arose out of reptile cells. RSV was pathogenic for adult reptiles. Reptile tumors did not contain a mature infectious virus. The tumors of 2 snakes were virogenic. The effect of increased temperature at the body level on the transformation of a symptomless viral infection into a viral disease is discussed in the evolutionary aspect.