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PubMed1984

Role of mink cell focus-inducing virus in leukemias induced by Friend ecotropic virus.

Recombinant viruses have been implicated in the pathogenesis of murine leukemias induced by a variety of long-latency retroviruses. Neonatal mice of several strains were inoculated with Friend ecotropic virus (F-Eco) and analyzed for the presence of mink cell focus-inducing (MCF) virus or DNA restriction enzyme fragments which were specific for Friend MCF virus (F-MCF). MCF virus was detected within 2 weeks of inoculation in NFS /N mice and at about 2 months after inoculation in BALB/c mice. Both of these strains developed erythroblastosis after inoculation with F-Eco. In contrast, MCF virus was not detected in F-Eco-inoculated C57BL mice. These mice were resistant to erythroblastosis but developed lymphoma or myelogenous leukemia or both at about 5 months after inoculation. Thus, although MCF viruses were associated with F-Eco erythroblastosis in NFS /N and BALB/c mice, they were not necessary for F-Eco-induced lymphoid or myeloid leukemias in C57BL mice. To investigate the association between resistance to erythroblastosis and absence of MCF virus, C57BL mice were inoculated with pseudotypic mixtures of F-Eco plus F-MCF; MCF virus replicated well in these mice, but the mice remained resistant to erythroblastosis. Furthermore, in genetic crosses between C57BL and NFS /N or BALB/c, some mice inherited resistance to F-Eco erythroblastosis without inheriting the C57BL resistance to the generation of MCF viruses. These results indicate that C57BL mice carry a gene for resistance to F-Eco erythroblastosis which is distinct from the C57BL genes which interfere with the generation of MCF viruses.

Animals↗
PubMed1977

Oncornavirus-induced sarcoma formation obscured by rapid development of lethal leukemia.

Injection i.v. of avian erythroblastosis virus (AEV) strain ES4 causes a high incidence of leukemia and the death of most of the inoculated chicks within 2 weeks. As found earlier, the virus is defective for replication and transforms bone marrow cultures in vitro, and surprisingly, also chick embryo fibroblasts. Inoculation of transformed AEV cells negative for virus production into newborn chicks induced the formation of sarcomas only, whereas cells superinfected with helper virus induced the formation of erythroblastosis in addition to sarcomas. The helper virus alone caused neither sarcomas nor erythroblastosis during the experimental period. These findings were explained by the hypothesis that AEV-induced erythroblastosis develops more rapidly than do AEV-induced sarcomas and that animals receiving i.v. injections die of the leukemia before sarcomas become detectable. The observation that animals receiving i.m. injections of AEV developed sarcomas at the site of injection strongly supports this concept. Most of the animals that received i.m. injections also developed an erythroblastosis that was delayed, however, in comparison to the animals receiving i.v. injections. Our data also suggest that the erythroblastosis induced by AEV does not suppress the formation of sarcomas in the same animal.

Alpharetrovirus↗
PubMed1992

Jaundice: clinical practice in 88,000 liveborn infants.

We reviewed jaundiced infants born between 1971 and 1989. Jaundice was diagnosed in infants whose serum bilirubin level was found to be 154 umol/l or greater. Of 88,137 livebirths, 10,944 (12.4%) were jaundiced. The most common aetiological factor was prematurity (20.3%), followed by ABO erythroblastosis (5.5%), sepsis (1.8%), Rh erythroblastosis (1.8%), bruising (1.3%), multifactorial (1.0%) and glucose-6-phosphate dehydrogenase deficiency (0.5%). In the remainder (67.8%) no cause was found or inadequate investigations were performed to determine a cause. During the period under review there was a significant increase (r = 0.91) in the proportion of newborn infants with jaundice of prematurity, in those not investigated (r = 0.92) and a decrease in the proportion with bruising (r = -0.90) as the cause. Phototherapy was used on 4,126 (37.7%) infants and exchange transfusion performed on 248 (2.3%). Causes of jaundice in infants requiring exchange transfusion were Rh erythroblastosis (108, 43.6%), ABO erythroblastosis (58, 23.4%), jaundice of prematurity (44, 17.7%) and a variety of causes in the remaining 38 (15.3%). Death occurred in 164 (1.5%) infants. In only 7 (4.3%), however, was the death possibly related to hyperbilirubinaemia or its treatment (Rh erythroblastosis (4), necrotizing enterocolitis following exchange transfusion (2) and pulmonary haemorrhage following exchange transfusion (1)). Phototherapy proved safe with no deaths attributable to its use.

Age Factors↗
PubMed1986

Differences in sequences encoding the carboxyl-terminal domain of the epidermal growth factor receptor correlate with differences in the disease potential of viral erbB genes.

Eleven recently isolated erbB-transducing viruses as well as avian erythroblastosis virus (AEV)-R (ES4) and AEV-H have been characterized for the type of disease they cause, their ability to transform fibroblasts in culture, their ability to cause disease in pedigrees of chicken that differ in susceptibility to erbB-induced erythroblastosis, and the structure of their erbB genes. Differences in each of the biological parameters correlated with differences in erbB sequences encoding the C-terminal domain of the epidermal growth factor receptor (EGFR). Seven viruses were strain restricted in their ability to induce erythroblastosis and did not transform fibroblasts. These seven viruses contained v-erbB genes encoding the complete C terminus of the EGFR. AEV-R and AEV-H were not pedigree restricted in their ability to induce erythroblastosis and could transform fibroblasts. These viruses contain v-erbB genes that lack codons for the immediate C terminus of the EGFR. Three viruses caused angiosarcoma and one caused fibrosarcoma. The angiosarcoma and fibrosarcoma-inducing viruses were not strain restricted and did not cause erythroblastosis. The v-erbB genes of each of these viruses contained extensive internal deletions or 3' truncations in sequences encoding the C-terminal domain of the EGFR.

Alpharetrovirus↗
PubMed1983

Jaundice: a 10 year review of 41,000 live born infants.

A review is presented of jaundiced newborn infants during the 10-year period to 1980. Included are those whose serum bilirubin level was 154 mumol/l or more. Of 41,057 live births, 4,406 (10.7%) infants had hyperbilirubinaemia. The most common (19.9;%) aetiological factor was prematurity, followed by ABO erythroblastosis 7.1%; sepsis 3.4%; Rhesus erythroblastosis 2.7%; bruising 2.2%; multifactorial 1.0% and glucose-6-phosphate dehydrogenase deficiency 0.5%. Treatment was not undertaken in 2,855 (64.7%) infants, but 1,419 (32.2%) received phototherapy alone, 122 (2.7%) infants received both exchange transfusion and phototherapy and 10 (0.2%) infants received exchange transfusion alone. Of the infants requiring exchange transfusion 50.0% had Rhesus erythroblastosis, 28.0% ABO erythroblastosis, 10.6% jaundice of prematurity and the remainder were due to a variety of causes. Sixty-three (1.4%) infants died, with two deaths being related to the hyperbilirubinaemia, as their death was due to necrotizing enterocolitis following exchange transfusion. Phototherapy proved safe with no deaths directly attributable to its use.

ABO Blood-Group System↗
PubMed1983

A new gene that controls the type of leukemia induced by Friend murine leukemia virus.

NB tropic Friend murine leukemia virus (F-MuLV) replicates equally well in BALB/c and C57BL mice inoculated as neonates but causes almost exclusively erythroblastosis in BALB/c mice and nonerythroid (lymphoid and myelogenous) leukemias in C57BL mice. The C57BL resistance to erythroblastosis appears to be controlled by a single dominant gene in first and second backcrosses to BALB/c. This resistance to erythroblastosis is distinct from other genes known to affect susceptibility to Friend virus including Fv-1, Fv-2, H-2, Rfv-3, Fv-4, and Rmcf. We suggest the name Fhe for the new gene controlling susceptibility to Friend helper virus erythroblastosis.

Animals↗
PubMed1983

Susceptibility to Friend helper virus leukemias in CXB recombinant inbred mice.

The seven CXB recombinant inbred strains were tested for susceptibility to Friend helper virus (F-MuLV) hematopoietic neoplasms. BALB/c and CXB-H mice develop erythroblastosis after neonatal inoculation with F-MuLV, while C57BL/6 and the six other RI strains develop lymphoma and myelogenous leukemia. This strain distribution pattern is different from that for H-2, Gpd-1 (linked to Fv-1), Fv-2, Rfv-3, and Cv (linked to Rmcf) but the same as that for Bv, the endogenous ecotropic virus of C57BL/6. However, analysis of crosses segregating Bv show that resistance to F-MuLV erythroblastosis is not linked to Bv. Disease-free survival is shortest for BALB/c mice, intermediate for CXB-H and CXB-J, and longest for C57BL/6 and the other RI strains. We conclude: (a) the major C57BL/6 gene for resistance to F-MuLV erythroblastosis is different from previously identified Friend virus restriction loci; (b) latency for F-MuLV leukemias is controlled by more than one gene; and (c) latency and susceptibility to F-MuLV erythroblastosis are not inherited concordantly in the CXB-RI strains.

Animals↗
PubMed1988

Proviral-activated c-erbB is leukemogenic but not sarcomagenic: characterization of a replication-competent retrovirus containing the activated c-erbB.

Avian leukosis virus (ALV) induces erythroblastosis in chickens by integrating its DNA into the host c-erbB locus and by activating expression of truncated c-erbB transcripts. Although there is a 100% correlation of c-erbB activation with ALV-induced erythroblastosis, direct evidence that the activated c-erbB is oncogenic has not been established. We have constructed a replication-competent retrovirus containing the activated c-erbB to investigate its transforming potential. The Rous c-erbB virus (REB-c) was constructed by inserting the activated c-erbB cDNA into a Rous sarcoma virus vector in place of src. When transfected into transformed quail fibroblasts (QT6), the REB-c construct stably integrates and expresses c-erbB-specific transcripts and produces infectious virus. The REB-c retrovirus produces short-latency polyclonal erythroblastosis in chickens. However, in contrast to avian erythroblastosis virus which contains v-erbB, the REB-c construct does not transform chicken embryo fibroblasts in vitro, nor does the REB-c virus produce sarcomas when injected into the wing web of chickens. Our results provide the first direct evidence that the activated c-erbB which lacks the amino-terminal extracellular domain but which retains the entire carboxy-terminal sequences is leukemogenic but not sarcomagenic.

Alpharetrovirus↗
PubMed1988

Molecular characterization of three erbB transducing viruses generated during avian leukosis virus-induced erythroleukemia: extensive internal deletion near the kinase domain activates the fibrosarcoma- and hemangioma-inducing potentials of erbB.

Three new erbB transducing viruses generated during avian leukosis virus-induced erythroblastosis have been cloned and sequenced, and their transforming abilities have been analyzed. Provirus 9134 E1 expresses an amino-terminally truncated erbB product that is analogous to the proviral insertionally activated c-erbB gag-erbB fusion product. This virus efficiently induces erythroblastosis, but does not transform fibroblasts in vitro or induce sarcomas in vivo. In contrast, virus 9134 S3 expresses an erbB product identical to the erbB product of 9134 E1, with the exception of a large internal deletion located between the kinase domain and the putative autophosphorylation site, P1. Interestingly, this virus is no longer capable of inducing erythroblastosis, but can induce both fibrosarcomas and hemangiomas in vivo. Provirus 9134 F3 has sustained an approximately 23-amino-acid carboxy-terminal truncation and is capable of inducing both erythroblastosis and sarcomagenesis. This virus expresses an erbB product with the shortest carboxy-terminal truncation sufficient to reveal the sarcomagenic potential of this protein. The distinct transforming properties of these viruses indicate that different structural domains of the erbB product confer distinct disease specificities.

Animals↗
PubMed1976

[Haemolytic disease of the new-born by blood-factor incompatibility other than Rh(d) and ABO (author's transl)].

Rare forms of incompatibility were observed over a period of 20 years in 41 (2%) of 2088 new-borns with haemolytic disease. Antibodies involved were anti-c (n = 27), anti-E (n = 6) and anti-K (n = 4), as well as one case each of anti-E + Fya, -C, -Fya and -Jka. Amniotic fluid was examined during pregnancy in nine cases, three children were given intra-uterine infusions, while in the remainder the haemolytic process was mild or only moderately severe. One infant died of toxoplasmosis, another one of immaturity and respiratory distress syndrome. Kernicterus was always prevented. In haemolytic disease of the newborn caused by anti-c and anti-E, prenatal damage is markedly rarer than with D erythroblastosis, but must be considered during the pregnancy. In anti-K haemolytic disease the severity of the disease is similar to that of D erythroblastosis. All three incompatibilities may lead to kernicterus in the first few days after birth so that exchange transfusions are often necessary. In most of the other incompatibilities the course is similar to that seen with ABO erythroblastosis.

Adult↗
PubMed1984

Dr. James A. Wolff. I. Early progress in treatment of Rh hemolytic disease.

Dr. James Wolff's interest in hematology began while he was assigned on the transfusion service in a field hospital in the European Theatre during World War II. His interest was increased during his pediatric residency at the Boston Children's Hospital (1945-1947). At that time, Dr. Louis Diamond was involved in his important studies on treatment of erythroblastosis fetalis by exchange transfusion. Drs. Farber and Diamond were also involved with the initial clinical trials of aminopterin for the treatment of acute leukemia. The concept of treating erythroblastosis fetalis by exchange transfusion grew from our understanding of the pathophysiology of this disease, as first explained by Philip Levine and Alexander Wiener. Three techniques of exchange transfusion were tried. Diamond's umbilical catheter technique, because of its relative ease and simplicity and because it could be used for multiple exchanges, soon became the accepted method for treating infants with erythroblastosis fetalis.

Erythroblastosis, Fetal↗
PubMed2002

Livebirths with placental hemorrhagic endovasculitis: interlesional relationships and perinatal outcomes.

BACKGROUND AND OBJECTIVE: Hemorrhagic endovasculitis (HEV) is a vasodisruptive alteration of fetal-placental blood vessels that has been associated with perinatal morbidity and mortality and abnormalities of growth and development. Clinicopathologic conditions that are often identified in pregnancies with HEV-affected placentas include villitis of unknown etiology, chorionic vessel thrombi, villous erythroblastosis, meconium staining, and maternal hypertension. The clinical implications of HEV are often disputed. This case-control study assesses the clinical relevance of HEV in placentas of viable infants and examines the interplay of coexistent intraplacental lesions. METHODS: We reviewed clinical records and slides from 104 livebirths with placentas affected by HEV above a specified severity level (cases) and 104 matched livebirths with placentas that were not affected by HEV (controls). We evaluated incidences of perinatal complications with increasing HEV severity indices in placentas with and without coexistent lesions. Interlesional relationships were established by matching HEV severity indices with severity indices of coexistent lesions. Hemorrhagic endovasculitis was subcategorized into active, bland, and healed forms and clustered capillary lesions (hemorrhagic villitis). RESULTS: Lesions that were frequently coexistent in HEV-affected placentas included villitis of unknown etiology, chorionic thrombi, villous fibrosis, erythroblastosis, and primary infarcts. Compared with the control group, the case group had higher incidences of abnormal fetal heart rate tracings (P <.003), fetal distress (P <.001), and growth restriction (P <.001). Increasing severities of HEV and coexistent lesions were associated with higher rates of perinatal complications. Complication rates were higher in HEV cases, with or without coexistent lesions. The complication rate was higher in cases affected by HEV and hemorrhagic villitis than in cases affected by HEV alone (P <.03). Significant interlesional relationships were evident between HEV and villitis of unknown etiology, chorionic thrombi, villous fibrosis, and erythroblastosis. CONCLUSIONS; Severe forms of HEV can occur in placentas of livebirths. The severity of HEV and associated lesions and the presence of hemorrhagic villitis have important clinical implications. Interlesional relationships between HEV and thrombotic, chronic inflammatory, and chronic vaso-occlusive lesions exist. Pregnancies with HEV-affected placentas with or without coexistent lesions are at risk for perinatal complications.

Chorionic Villi↗
PubMed2005

Stillbirths with placental hemorrhagic endovasculitis: a morphologic assessment with clinical implications.

CONTEXT: Hemorrhagic endovasculitis (HEV) is a vasodisruptive alteration affecting fetal-placental blood vessels of all calibers. Hemorrhagic endovasculitis is found in association with stillbirth and abnormalities of growth and development in livebirths. The role of HEV in the pathogenesis of these conditions is not known. OBJECTIVE: To further understand these events, we compare clinicopathologic features of HEV-affected placentas from stillbirths with those from livebirth pregnancies. Additionally, we assess the relationship of morphologic forms of HEV to clinical events and time of fetal death in utero and evaluate the significance of extensive versus localized HEV lesions in placentas of stillbirths. DESIGN: We reviewed the clinical records and slides from 119 stillbirths with placentas affected by HEV classified above a specified severity level (cases) and 119 matched stillbirths with placentas not affected by HEV (controls). A subset of 21 stillbirth placentas exhibiting focal HEV lesions was similarly evaluated. Slides were graded for HEV, villitis of unknown etiology, chorionic thrombi, villous fibrosis, erythroblastosis, and lesions indicative of maternal hypertension. Hemorrhagic endovasculitis was subcategorized into active, bland, and healed forms and clustered capillary lesions (hemorrhagic villitis). Focal, segmental, and diffuse patterns of villous fibrosis were delineated. Interlesional relationships were established by matching HEV severity indices with severity indices of co-existing lesions. Timing of fetal death was determined by published criteria. Data were analyzed for significance using chi2 and t tests. Results were compared with published analyses of livebirths with placental HEV. RESULTS: Lesions occurring with significant frequency in HEV-affected (case) placentas include villitis of unknown etiology, chorionic thrombi, villous fibrosis, erythroblastosis, and meconium staining. Interlesional relationships were evident between HEV and villous fibrosis, villitis of unknown etiology, and chorionic thrombi. Growth restriction was more common in case versus control infants (P = .02). A segmental pattern of villous fibrosis predominated in cases versus controls and within the case group (P < .001). Time to delivery after fetal death was longer in cases than controls. Active-vasodestructive forms of HEV correlate with shorter intervals of intrauterine retention, whereas bland forms correlate with longer intervals (P = .04). Placentas with focal HEV were associated with coexisting chorionic thrombi and villous fibrosis but not with fetal growth restriction. CONCLUSIONS: Patterns of interlesional interplay are similar in HEV-affected placentas of livebirths and stillbirths. This suggests that the pathogenesis of infant morbidity and mortality is similar in both groups. Active-vasodestructive forms of HEV may precede whereas bland forms may follow intrauterine demise. The segmental pattern of villous fibrosis and high incidences of growth restriction, erythroblastosis, and meconium in cases suggests a chronicity of adverse intrauterine events that may precede fetal loss. Stillbirths with focal HEV lesions are probably not at risk.

Adult↗
PubMed1981

Histone H5 in the immature blood cells of chickens with leukosis induced by avian leukosis virus strain E26.

Whole histone was isolated from the immature cells of the peripheral blood of White Leghorn chickens, line 151, with leukosis experimentally induced by avian leukosis virus, strain E26 (ALV-E26). Histone H5 was demonstrated in all samples of these cells and was characterized by electrophoresis in polyacrylamide gel, extraction with perchloric acid, amino acid analysis, and immunodiffusion in agarose gel. Histone H5 was not detected in the myeloblasts of chickens with myeloblastosis caused by the avian myeloblastosis virus. It was concluded that the immature cells (IBC-E26) obtained from the peripheral blood of chickens responding positively to ALV-E26 belonged to the erythroid blood cell series and that ALV-E26 induced in vivo erythroblastosis but not myeloblastosis in chickens. The relative amount of histone H5 in IBC-E26 was two times higher than that in the erythroblasts obtained from the peripheral blood of chickens with erythroblastosis caused by avian erythroblastosis virus, strain R of Engelbreth-Holm. Thus the erythroblasts in the circulating blood of chickens with leukosis induced by ALV-E26 seemed to be more differentiated.

Alpharetrovirus↗
PubMed1979

DNA and RNA from uninfected vertebrate cells contain nucleotide sequences related to the putative transforming gene of avian myelocytomatosis virus.

The avian carcinoma virus MC29 (MC29V) contains a sequence of approximately 1,500 nucleotides which may represent a gene responsible for tumorigenesis by MC29V. We present evidence that MC29V has acquired this nucleotide sequence from the DNA of its host. The host sequence which has been incorporated by MC29V is transcribed into RNA in uninfected chicken cells and thus probably encodes a cellular gene. We have prepared radioactive DNA complementary to the putative MC29V transforming gene (cDNA(mc) (29)) and have found that sequences homologous to cDNA(mc) (29) are present in the genomes of several uninfected vertebrate species. The DNA of chicken, the natural host for MC29V, contains at least 90% of the sequences represented by cDNA(mc) (29). DNAs from other animals show significant but decreasing amounts of complementarity to cDNA(mc) (29) in accordance with their evolutionary divergence from chickens; the thermal stabilities of duplexes formed between cDNA(mc) (29) and avian DNAs also reflect phylogenetic divergence. Sequences complementary to cDNA(mc) (29) are transcribed into approximately 10 copies per cell of polyadenylated RNA in uninfected chicken fibroblasts. Thus, the vertebrate homolog of cDNA(mc) (29) may be a gene which has been conserved throughout vertebrate evolution and which served as a progenitor for the putative transforming gene of MC29V. Recent experiments suggest that the putative transforming gene of avian erythroblastosis virus, like that of MC29V, may have arisen by incorporation of a host gene (Stehelin et al., personal communication). These findings for avian erythroblastosis virus and MC29V closely parallel previous results, suggesting a host origin for src (D. H. Spector, B. Baker, H. E. Varmus, and J. M. Bishop, Cell 13:381-386, 1978; D. H. Spector, K. Smith, T. Padgett, P. McCombe, D. Roulland-Dussoix, C. Moscovici, H. E. Varmus, and J. M. Bishop, Cell 13:371-379, 1978; D. H. Spector, H. E. Varmus, and J. M. Bishop, Proc. Natl. Acad. Sci. U.S.A. 75:4102-4106, 1978; D. Stehelin, H. E. Varmus, J. M. Bishop, and P. K. Vogt, Nature [London] 260:170-173, 1976), the gene responsible for tumorigenesis by avian sarcoma virus. Avian sarcoma virus, avian erythroblastosis virus, and MC29V, however, induce distinctly different spectra of tumors within their host. The putative transforming genes of these viruses share no detectable homology, although sequences homologous to all three types of putative transforming genes occur and are highly conserved in the genomes of several vertebrate species. These data suggest that evolution of oncogenic retroviruses has frequently involved a mechanism whereby incorporation and perhaps modification of different host genes provides each virus with the ability to induce its characteristic tumors.

Alpharetrovirus↗
PubMed1985

Roles of helper and defective retroviral genomes in murine erythroleukemia: studies of spleen focus-forming virus in the absence of helper.

Retroviruses that cause acute oncogenesis are generally complexes of a replication-competent helper virus and a replication-defective component. However, the pure defective components have not been previously available. We prepared the defective spleen focus-forming virus component of Rauscher erythroleukemia virus (R-SFFV) by transfecting a colinear R-SFFV DNA clone into a retroviral packaging cell line (psi 2 cells). The transfected cells released virus (psi 2/SFFV) that was free of helper virus and that induced erythropoietin-dependent erythroid burst formation in bone marrow cultures. When injected into normal adult NIH/Swiss mice in moderate doses, psi 2/SFFV caused a rapid splenic erythroblastosis that regressed. Extensive erythroblastosis could be maintained by repeated injections of psi 2/SFFV into anemic mice or by the addition of a helper virus. We conclude that R-SFFV alone causes proliferation but not immortalization of a population of erythroblasts that is normally replenished from a precursor stem cell pool. Because these precursor cells are inefficiently infected, a single moderate inoculum of psi 2/SFFV causes a wave of erythroblastosis. The properties of the proliferating erythroblasts are substantially determined by the R-SFFV viral component.

Animals↗
PubMed1987

The membrane glycoprotein of Friend spleen focus-forming virus: evidence that the cell surface component is required for pathogenesis and that it binds to a receptor.

The leukemogenic membrane glycoprotein of Friend spleen focus-forming virus (SFFV) has an apparent Mr of 55,000 (gp55), is encoded by a recombinant env gene, and occurs on cell surfaces and in intracellular organelles. There is evidence that the amino-terminal region of gp55 forms a dualtropic-specific domain that is connected to the remainder of the glycoprotein by a proline-rich linker (C. Machida, R. Bestwick, B. Boswell, and D. Kabat, Virology 144:158-172, 1985). Using the colinear form of a cloned polycythemic strain of SFFV proviral DNA, we constructed seven in-phase env mutants by insertion of linkers and by a deletion. The mutagenized SFFVs were transfected into fibroblasts and were rescued by superinfection with a helper murine leukemia virus. Four of the mutants cause erythroblastosis. These include one with a 6-base-pair (bp) insert in the ecotropic-related sequence near the 3' end of the gene, two with a 12- or 18-bp insert in the region that encodes the proline-rich linker, and one with a 6-bp insert in the dualtropic-specific region. The other mutants (RI, Sm1, and Sm2) are nonpathogenic and contain lesions in dualtropic-specific region. The other mutants (RI, Sm1, and Sm2) are nonpathogenic and contain lesions in dualtropic-specific sequences that are highly conserved among strains of SFFV. A pathogenic revertant (RI-rev) was isolated from one mouse that developed erythroblastosis 3 weeks after infection with RI. RI-rev contains a second-site env mutation that affects the same domain as the primary mutation does and that increases the size of the encoded glycoprotein. All pathogenic SFFVs encode glycoproteins that are expressed on cell surfaces, whereas the nonpathogenic glycoproteins are exclusively intracellular. The pathogenic SFFVs also specifically cause a weak interference to superinfection by dualtropic MuLVs. These results are compatible with the multidomain model for the structure of gp55 and suggest that processing of gp55 to plasma membranes is required for pathogenesis. The amino-terminal region of gp55 binds to dualtropic murine leukemia virus receptors, and this interaction is preserved in the SFFV mutants that cause erythroblastosis.

Animals↗
PubMed1998

Differential selection of cells with proviral c-myc and c-erbB integrations after avian leukosis virus infection.

Avian leukosis virus (ALV) infection induces bursal lymphomas in chickens after proviral integration within the c-myc proto-oncogene and induces erythroblastosis after integration within the c-erbB proto-oncogene. A nested PCR assay was used to analyze the appearance of these integrations at an early stage of tumor induction after infection of embryos. Five to eight distinct proviral c-myc integration events were amplified from bursas of infected 35-day-old birds, in good agreement with the number of transformed bursal follicles arising with these integrations. Cells containing these integrations are remarkably common, with an estimated 1 in 350 bursal cells having proviral c-myc integrations. These integrations were clustered within the 3' half of c-myc intron 1, in a pattern similar to that observed in bursal lymphomas. Bone marrow and spleen showed a similar number and pattern of integrations clustered within 3' c-myc intron 1, indicating that this region is a common integration target whether or not that tissue undergoes tumor induction. While all tissues showed equivalent levels of viral infection, cells with c-myc integrations were much more abundant in the bursa than in other tissues, indicating that cells with proviral c-myc integrations are preferentially expanded within the bursal environment. Proviral integration within the c-erbB gene was also analyzed, to detect clustered c-erbB intron 14 integrations associated with erythroblastosis. Proviral c-erbB integrations were equally abundant in the bone marrow, spleen, and bursa. These integrations were randomly situated upstream of c-erbB exon 15, indicating that cells carrying 3' intron 14 integrations must be selected during induction of erythroblastosis.

Animals↗