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1.
Acquisition of oncogenicity by endogenous mouse type C viruses: effects of variations in env and gag genes.
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Several dual-tropic isolates derived from the thymuses of preleukemic or leukemic AKR mice and a more recrnt group of viruses generated by in vitro or in vivo passage of a poorly infectious endogenous virus of C3H mouse cells have been shown to be highly oncogenic. By analysis of the immunological properties of their gag gene-coded structural proteins, each of the AKR-derived isolates and two dual-tropic C3H-derived isolates were found to closely resemble AKR murine leukemia virus. In contrast, gag gene-coded proteins of two other leukemogenic isolates of C3H origin, including one ecotropic and one dual-tropic virus, were indistinguishable from those of Moloney murine leukemia virus. All of the oncogenic isolates, including those of AKR and C3H origin, were found to possess common envelope glycoprotein determinants of a unique class not shared by the nononcogenic ecotropic viruses from which they were derived. These findings support the possibility that oncogenic variants of endogenous ecotropic mouse type C viruses are derived by genetic recombination. This recombinational event appears to involve the acquisition, by different ecotropic viruses, of a common class of endogenous virus-coded envelope glycoprotein determinants which are presumably required, but not necessarily sufficient, for oncogenicity. 相似文献
2.
Primate retroviruses: envelope glycoproteins of endogenous type C and type D viruses possess common interspecies antigenic determinants.
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The major 70,000- to 80,000-molecular-weight envelope glycoproteins of the squirrel monkey retrovirus, Mason-Pfizer monkey virus, and M7 baboon virus and the related endogenous feline virus, RD114, were isolated and immunologically characterized. Immunoprecipitation and competition immunoassay analysis revealed these viral envelope glycoproteins to possess several distinct classes of immunological determinants. These include species-specific determinants, group-specific antigenic determinants unique to endogenous primate type C viruses, and group-specific determinants for type D viruses such as Mason-Pfizer monkey virus and squirrel monkey retrovirus. In addition, a class of broadly reactive antigenic determinants shared by envelope glycoproteins of both type C viruses of the baboon/RD114 group and type D viruses of the Mason-Pfizer monkey virus/squirrel monkey virus group are described. Other mammalian oncornaviruses tested, including isolates of nonprimate origin and representative type B viruses, lacked these determinants. The demonstration of antigenic determinants specific to envelope glycoproteins of type C and type D primate viruses indicates either that these viruses are evolutionarily related or that genetic recombination occurred between their progenitors. Alternatively, endogenous type D oncornaviruses may be replication defective, and acquisition of endogenous type C viral genetic sequences coding for envelope glycoprotein determinants may be necessary for their isolation as infectious virus. 相似文献
3.
Two distinct endogenous type C viruses isolated from the asian rodent Mus cervicolor: conservation of virogene sequences in related rodent species. 总被引:10,自引:0,他引:10
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The cocultivation of a lung cell line from the Southeast Asian mouse Mus cervicolor with cells from heterologous species has resulted in the isolation of two new distinct type C viruses. Both viruses are endogenous to M. cervicolor and are present in multiple copies in the cellular DNA of these mice. One of the viruses, designated M. cervicolor type CI, replicates readily in the SIRC rabbit cell line and is antigenically related to the infectious primate type C viruses isolated from a woolly monkey (simian sarcoma-associated virus) and gibbon apes (gibbon ape leukemia virus). This virus is also closely related by both immunological and nucleic acid hybridization criteria to a type C virus previously isolated from a second Asian murine species, Mus caroli. The isolation of the M. cervicolor type C I virus thus provides further evidence that the infectious primate type C viruses originated by trans-species infection of primates by an endogenous virus of mice. The second virus, designated M. cervicolor type C II, replicates well in various cell lines derived from the laboratory mouse Mus musculus. While antigenically related to type C viruses derived from M. musculus, the M. cervicolor type C II virus isolate can be readily distinguished from standard murine leukemia viruses. Both new type C viruses from M. cervicolor are unrelated to the previously described retrovirus (M432) isolated from the same Mus species. The DNA of M. cervicolor therefore contains multiple copies of at least three distinct classes of endogenous viral genes. An examination of the cellular DNA of other rodent species for nucleic acid sequences related to the genomes of both M. cervicolor type C I and II reveals that both viruses have been highly conserved evolutionarily, and that other species of rodents, such as laboratory mice and rats, contain endogenous virogenes related to those in the DNA of M. cervicolor. 相似文献
4.
5.
Endogenous type C RNA virus of Odocoileus hemionus, a mammalian species of New World origin. 总被引:2,自引:0,他引:2
Type C RNA viruses have been isolated from several Old World vertebrates, and an even larger number of Old World species have been shown to contain endogenous viral genetic sequences. The present report describes the first isolation of type C virus endogenous to a species originating in the New World. This virus, isolated from cells of the Columbian black-tailed deer, Odocoileus hemionus, is shown to possess genetic sequences in common with DNA of its species of origin. While it shares biochemical and immunologic characteristics with other mammalian type C viruses, its immunologic properties readily distinguish it from known endogenous viruses. 相似文献
6.
Rat sequences of the Kirsten and Harvey murine sarcoma virus genomes: nature, origin, and expression in rat tumor RNA. 总被引:19,自引:19,他引:0
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Two murine sarcoma viruses, the Kirsten and the Harvey, were isolated by passage of mouse type C leukemia viruses through rats. These sarcoma viruses have genomes containing portions of their parental type C mouse leukemia virus genomes, in stable association with specific rat cellular sequences that we find to be quite likely not those of a rat type C leukemia virus. To determine if these murine sarcoma viruses provide a model relevant to the events occurring in spontaneous tumors, we have hybridized DNA and RNA prepared from rat tumors and normal rat tissues to [3H]DNA prepared from the Kirsten murine sarcoma virus. We have also hybridized these rat tissue nucleic acids to [3H]DNA prepared from a respresentative endogenous rat type C leukemia virus, the WFU (Wistar-Furth). Sarcoma-viral rat cellular sequences and endogenous rat leukemia viral sequences were detected in the DNA of both tumor and normal tissues, with no evidence of either gene amplification or additional sequences being present in tumor DNA. Sarcoma-viral rat cellular sequences and endogenous rat leukemia viral sequences were detected at elevated concentrations in the RNA of many rat tumors and in specific groups of normal tissues. 相似文献
7.
Radiommunoassays for the 70,000-molecular-weight glycoproteins of endogenous mouse type C viruses: viral antigen expression in normal mouse tissues and sera. 总被引:26,自引:0,他引:26
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Genetic information coding for type C RNA viruses is transmitted within the DNA of mouse cells. At least three endogenous viruses have so far been immunologically distinguished by radioimmunoassays for their 12,000-molecular-weight polypeptides (p12). In the present study, the 70,000-molecular-weight glycoproteins (gp70) of three prototype viruses were purified, and competition radioimmunoassays were developed for each. By use of these immunoassays, the antigenic determinants of gp70's of different classes of endogenous virus, isolated from the same and from a variety of other mouse strains, were readily discriminated. In contrast, viruses of the same class were indistinguishable. These findings further document the existence of three distinct endogenous viruses of mouse cell. The levels of type C viral gp70 were quantitated in tissues and sera of several inbred strains. The pattern of immunological reactivity of the gp70 detected in serum was indistinguishable from that of the viral gp70 partially purified from tissues of the same strain. Moreover, in each case it was indistinguishable from that of a specific class of endogenous virus. In virus-negative tissues of BALB/c and NIH Swiss mice, the viral gp70 detected was shown to be representative of a class III endogenous virus whose p12 polypeptide was also expressed by the same cells. 相似文献
8.
Chimeric dengue type 2 (vaccine strain PDK-53)/dengue type 1 virus as a potential candidate dengue type 1 virus vaccine 总被引:11,自引:0,他引:11
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Huang CY Butrapet S Pierro DJ Chang GJ Hunt AR Bhamarapravati N Gubler DJ Kinney RM 《Journal of virology》2000,74(7):3020-3028
We constructed chimeric dengue type 2/type 1 (DEN-2/DEN-1) viruses containing the nonstructural genes of DEN-2 16681 virus or its vaccine derivative, strain PDK-53, and the structural genes (encoding capsid protein, premembrane protein, and envelope glycoprotein) of DEN-1 16007 virus or its vaccine derivative, strain PDK-13. We previously reported that attenuation markers of DEN-2 PDK-53 virus were encoded by genetic loci located outside the structural gene region of the PDK-53 virus genome. Chimeric viruses containing the nonstructural genes of DEN-2 PDK-53 virus and the structural genes of the parental DEN-1 16007 virus retained the attenuation markers of small plaque size and temperature sensitivity in LLC-MK(2) cells, less efficient replication in C6/36 cells, and attenuation for mice. These chimeric viruses elicited higher mouse neutralizing antibody titers against DEN-1 virus than did the candidate DEN-1 PDK-13 vaccine virus or chimeric DEN-2/DEN-1 viruses containing the structural genes of the PDK-13 virus. Mutations in the envelope protein of DEN-1 PDK-13 virus affected in vitro phenotype and immunogenicity in mice. The current PDK-13 vaccine is the least efficient of the four Mahidol candidate DEN virus vaccines in human trials. The chimeric DEN-2/DEN-1 virus might be a potential DEN-1 virus vaccine candidate. This study indicated that the infectious clones derived from the candidate DEN-2 PDK-53 vaccine are promising attenuated vectors for development of chimeric flavivirus vaccines. 相似文献
9.
Isolation from BALB/c mouse cells of a structural polypeptide of a third endogenous type C virus 总被引:6,自引:0,他引:6
A 12,000 molecular weight type C viral polypeptide, p12, has been isolated from BALB/c mouse cells. This polypeptide is shown to be immunologically distinct from the p12 antigens of two previously described endogenous viruses of BALB/c cells. It is, however, indistinguishable from a viral antigen expressed in NIH Swiss mouse cells and present in type C viruses isolated from NIH Swiss mice. The expression of endogenous viruses containing each of the three distinguishable p12 antigens is shown to be differentially affected by two classes of chemical inducers, halogenated pyrimidines and inhibitors of protein synthesis. The present findings thus provide evidence for the existence of genetic information of three distinguishable endogenous viruses within cells of the BALB/c strain. 相似文献
10.
Genetic transmission of retroviral genes and cellular oncogenes 总被引:1,自引:0,他引:1
G J Todaro R Callahan U R Rapp J E De Larco 《Proceedings of the Royal Society of London. Series B, Containing papers of a Biological character. Royal Society (Great Britain)》1980,210(1180):367-385
Several different families of retrovirus genome have been found to exist, each in multiple copies, in the cellular DNA of rodents and primates. There are at least four distinct families of genome in rodents: two type C families, the MTV family and another related to mouse type A particles. In primates there are also at least two families of endogenous type C virogenes and a third type D virogene family. Both in rodents and in primates, the virus-related sequences constitute almost 0.1% of the cellular genome. We have been able to generate transforming viruses, starting with endogenous mouse 'helper' type C viruses by passing them through chemically transformed mouse cells and selecting for variant viruses that have acquired the ability to induce normal cells to display anchorage-independent growth. These viruses produce both sarcomas and carcinomas in the animal; clones that produce only pulmonary carcinomas have also been selected. These presumably have arisen by recombination between the helper and 'transforming' sequences derived from the cells. Moloney sarcoma virus-transformed cells produce a new peptide, called sarcoma growth factor (SGF), that makes normal cells take on some of the properties of transformed cells. Studies with temperature-sensitive viral mutants show that the production of SGF is under the control of the transforming genes of the sarcoma virus. 相似文献
11.
Extensive envelope heterogeneity of simian immunodeficiency virus in tissues from infected macaques. 总被引:7,自引:6,他引:1
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The extent of virus genetic variation within tissues and peripheral blood mononuclear cells (PBMC) from two simian immunodeficiency virus (SIV)-infected macaques was analyzed. The products of PCR amplification of two regions, region 1 (SIV V1 region) and region 2 (region corresponding to the human immunodeficiency virus V3 cysteine loop and part of the C3 region immediately downstream), of the SIV envelope were examined for single-stranded conformation polymorphism followed by sequence analysis of selected clones. The V1 region of the SIV envelope of viruses present within lymphoid tissues displayed extensive heterogeneity, while viral populations within the PBMC and brain appeared to be less variable. Region 2 heterogeneity in both animals was generally confined to three residues in a tissue-specific manner. In addition, virus from the brains of both animals appeared to be distinct compared with viruses present in other tissues and PBMC of the same animal, both in the pattern of PCR-single-stranded conformation polymorphism SCP and in the sequence of region 2. These studies revealed that the tissues of SIV-infected macaques were a reservoir for viral variants distinct from those seen in PBMC. 相似文献
12.
A single point mutation in the envelope gene is responsible for replication and XC fusion deficiency of the endogenous ecotropic C3H/He murine leukemia virus and for its repair in culture. 总被引:2,自引:2,他引:0
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The molecular basis has been determined for differences in infectivity and XC phenotype of endogenous ecotropic murine leukemia virus of the low-leukemia mouse strain C3H/He, its relative in the high-leukemia mouse strain AKR, and highly infectious, XC-positive C3H virus variants selected in vitro. Endogenous ecotropic type C virus induced by iododeoxyuridine from the nontransformed C3H/10T1/2 cell line is XC negative and replication deficient. In contrast, viruses produced late after iododeoxyuridine induction in chemically transformed C3H/10T1/2 cells (MCA5) are XC positive and infectious. XC-negative viruses can be converted to XC-positive viruses by being grown in certain transformed cell lines. We have cloned the endogenous ecotropic provirus of C3H/He from MCA5 cells, which is XC negative and replication deficient, as well as two XC-positive C3H proviruses derived by in vitro conversion. Fragment exchange between the XC-negative molecular clone p110 and the XC-positive AKR virus clone p623 revealed that the defect in p110 lies 3' of the SalI site located in the pol region. Nucleotide sequencing established that the C3H p110 provirus was integrated within the R region of an endogenous VL30 long terminal repeat (LTR) in reverse orientation and that the virus differed from the infectious AKR p623 provirus by a point mutation, substituting Lys for Arg at the potential precursor cleavage site for gp70 and p15E. In vitro-converted XC-positive C3H proviral clones 3211 and 4211 are identical to XC-negative C3H p110, except that they have Arg at this site and the normal cleavage site is thus regenerated in these clones. The XC-negative C3H p110 was blocked in processing of Pr85env, whereas clones 3211 and 4211 had normal cleavage of the env precursor into gp70. Both the XC-negative C3H provirus and the in vitro-converted XC-positive C3H proviruses had a single copy of a 99-base-pair enhancer element in the LTR, whereas two copies of this sequence are present in the AKR proviral LTR. Substitution of Arg for Lys at the envelope precursor processing site of C3H p110 by site-directed mutagenesis is sufficient by itself to convert the virus to the XC-positive replication-competent phenotype. Thus, we have established that a single point mutation at the processing site of the envelope precursor protein Pr85 is responsible for the difference in the infectivity and XC phenotype of endogenous ecotropic murine leukemia virus from C3H/He and AKR mice and that the basis for in vitro conversion is a mutation at this site. 相似文献
13.
A novel species of 30S RNA has been detected in a variety of mouse cell lines. The 30S RNA is specifically packaged by helper-independent type C viruses propagated in such cells. Nucleic acid hybridization detects no homology between the 30SRNA and the genomic RNA of helper-independent mouse type C viruses. The properties of the 30S RNA suggest that it is a defective endogenous mouse type C virus and that it is analogous to a previously described class of defective endogenous rat type C virus, which has been shown previously to be the progenitor of Kirsten and Harvey murine sarcoma viruses. 相似文献
14.
Envelope-binding domain in the cationic amino acid transporter determines the host range of ecotropic murine retroviruses. 总被引:35,自引:29,他引:6
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Infection of rodent cells by ecotropic type C retroviruses requires the expression of a cationic amino acid transporter composed of multiple membrane-spanning domains. By exchanging portions of cDNAs encoding the permissive mouse and nonpermissive human transporters and examining their abilities to specify virus infection upon expression in human 293 cells, we have identified the amino acid residues in the extracellular loop connecting the fifth and sixth membrane-spanning segments of the mouse transporter that are required for both envelope gp70 binding and infection. These findings strongly suggest that the role of the mouse transporter in determining infection is to provide an envelope-binding site. This role is analogous to those of host membrane proteins composed of a single membrane-spanning domain that serve as binding proteins or receptors for other enveloped viruses such as human immunodeficiency virus, Epstein-Barr virus, and murine and human coronaviruses. 相似文献
15.
Yellow fever/Japanese encephalitis chimeric viruses: construction and biological properties 总被引:10,自引:0,他引:10
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A system has been developed for generating chimeric yellow fever/Japanese encephalitis (YF/JE) viruses from cDNA templates encoding the structural proteins prM and E of JE virus within the backbone of a molecular clone of the YF17D strain. Chimeric viruses incorporating the proteins of two JE strains, SA14-14-2 (human vaccine strain) and JE Nakayama (JE-N [virulent mouse brain-passaged strain]), were studied in cell culture and laboratory mice. The JE envelope protein (E) retained antigenic and biological properties when expressed with its prM protein together with the YF capsid; however, viable chimeric viruses incorporating the entire JE structural region (C-prM-E) could not be obtained. YF/JE(prM-E) chimeric viruses grew efficiently in cells of vertebrate or mosquito origin compared to the parental viruses. The YF/JE SA14-14-2 virus was unable to kill young adult mice by intracerebral challenge, even at doses of 10(6) PFU. In contrast, the YF/JE-N virus was neurovirulent, but the phenotype resembled parental YF virus rather than JE-N. Ten predicted amino acid differences distinguish the JE E proteins of the two chimeric viruses, therefore implicating one or more residues as virus-specific determinants of mouse neurovirulence in this chimeric system. This study indicates the feasibility of expressing protective antigens of JE virus in the context of a live, attenuated flavivirus vaccine strain (YF17D) and also establishes a genetic system for investigating the molecular basis for neurovirulence determinants encoded within the JE E protein. 相似文献
16.
Temperature-Sensitive Mutants of Murine Leukemia Virus IV. Further Physiological Characterization and Evidence for Genetic Recombination 总被引:7,自引:5,他引:2
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Several temperature-sensitive mutants of the Rauscher strain of murine leukemia virus representing three distinct physiological groups have been further characterized. Genetic recombination between different pairs of these mutants has been demonstrated. Several representative genetic recombinants were isolated and shown to replicate equally well at the permissive (31 C) and nonpermissive (38 C) temperatures and to have serological characteristics of the wild-type parental virus. Alternative models for the mechanisms involved in recombination between type C RNA viruses are discussed. 相似文献
17.
Characterizatiion of rat genetic sequences of Kirsten sarcoma virus: distinct class of endogenous rat type C viral sequences. 总被引:4,自引:0,他引:4
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The nucleic acid sequences found in DNA and RNA from rat cells which are homologous to Kirsten sarcoma virus have been characterized. The homologous sequences are present in multiple copies per diploid rat cellular genome in a variety of different rat cellular dna's. In certain cells that constitutively express only low levels of sequences homologous to Kirsten sarcoma virus, bromodeoxyuridine treatment leads to the expression of high levels of these sequences in RNA. Supernatants from cell lines producing the sequences homologous to Kirsten sarcoma virus contain high levels of these sequences which are purified to the same degree as the previously known rat type C viral nucleic acid sequences by type C particles being released from such cells. The results indicate that the sequences in rat cells homologous to Kisten sarcoma virus have three characteristics of known mammalian type C viruses, and suggest that at least part of Kirsten sarcoma virus rat-derived sequences represent a distinct class of endogenous rat type C virus that has no detectable homology to the other known class of endogenous rat type C virus. 相似文献
18.
H C Morse B A Taylor C A Kozak T M Chused S O Sharrow J W Hartley E Stockert 《Journal of immunology (Baltimore, Md. : 1950)》1982,128(5):2111-2115
XenCSA and GIX are two cell surface antigens related to the major envelope glycoproteins (gp70) of murine leukemia viruses. The levels of expression of these gp70 determinants were assessed in 36 recombinant inbred mouse strains and selected backcrosses derived from crosses between C57BL/6 with DBA/2 and C3H/He. These two antigens segregated in backcross mice and showed a different strain distribution pattern among the recombinant inbred mice, demonstrating that XenCSA and GIX are distinct genetic markers for different endogenous gp70 sequences. It was also shown that independent sets of gene regulate the expression of XenCSA and GIX. 相似文献
19.
Comparative studies on the structural phosphoproteins of mammalian type C viruses. 总被引:14,自引:14,他引:0
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The major phosphoprotein common to woolly monkey sarcoma virus, gibbon ape lymphosarcoma virus, and type C viruses of the lower mammalian species (mouse, rat, cat), with the exception of the endogenous cat virus (RD-114), is the polypeptide of about 12,000 molecular weight. The protein-phosphate bond in this polypeptide of several viruses is of the phosphoserine variety excepting gibbon ape virus, which contains both phosphoserine and phosphothreonine. The primary phosphoprotein of RD-114 virus and the endogenous baboon type C virus, on the other hand, is the polypeptide of about 15,000 molecular weight which contains phosphothreonine as its phosphoamino acid. A second major phosphoprotein of molecular weight of 10,000 is detected only in viruses genetically related to rat species including those derived from the RPL cell line, from Sprague-Dawley rat embryo cells, and the Kirsten mouse sarcoma virus which was recovered from a mouse erythroblastosis virus after in vivo propagation through rat. These phosphorylated polypeptides of molecular weight 15,000, 12,000, or 10,000 are present in the virion structure in several different but nonrandom phosphorylated states. 相似文献
20.
Nell S Lurain Andrea M Fox Heather M Lichy Sangeeta M Bhorade Carl F Ware Diana D Huang Sau-Ping Kwan Edward R Garrity Sunwen Chou 《Virology journal》2006,3(1):1-18