Frequent hereditable shutdown of murine retrovirus gene expression in murine cell lines.

Bestwick, Richard K.; Machida, Curtis A.; Polonoff, E; Kabat, David

doi:10.1128/mcb.4.5.908

Cited by 11 publications

(4 citation statements)

References 39 publications

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“…In con- Spleen cells producing FV were detected by infectious center titration using a focal immunoassay (49) and were compared with neutralizing anti-FV antibody titers (47) trast, Rfv-3sJs mice such as BALBjc or (BALBjc x A)F 1 mice had no detectable antibody and no decrease in expression of infectious virus (Table 2). Expression of infectious Friend virus often spontaneously ceased both in leukemia cell lines in vitro and in leukemic spleen cell populations in vivo (24,27,28). Thus, Rfv-3 appeared to operate through induction of antiviral antibodies.…”

Section: Recovery From Fv Leukemiamentioning

confidence: 99%

“…Thus, Rfv-3 appeared to operate through induction of antiviral antibodies. The effect of the antibodies in altering virus expression in Rfv_3r/s mice might thus be due to blocking the cycles of reinfection of spleen cells which probably occur following loss of infectious virus production in leukemic spleen cell populations (28). It was postulated initially that these antibodies could induce capping and internalization of viral cell surface antigens with subsequent inability to release infectious virus (24); however, experimental efforts to prove this hypothesis were unsuccessful.…”

Section: Recovery From Fv Leukemiamentioning

confidence: 99%

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Host Genetic Control of Spontaneous and Induced Immunity to Friend Murine Retrovirus Infection

Chesebro

Miyazawa²,

Britt³

1990

Annu. Rev. Immunol.

118

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Section: Recovery From Fv Leukemiamentioning

confidence: 99%

Section: Recovery From Fv Leukemiamentioning

confidence: 99%

Host Genetic Control of Spontaneous and Induced Immunity to Friend Murine Retrovirus Infection

Chesebro

Miyazawa²,

Britt³

1990

Annu. Rev. Immunol.

118

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“…Such a mechanism would be compatible with the rapid reduction in hGH production that we have observed in single cell clones. Instabilities of retroviral expression have been described previously (5,7,11,17,25).…”

Section: Fig 5 Protein Immunoblot Analysis Of Shutoff Viruses That mentioning

confidence: 99%

Ping-pong amplification of a retroviral vector achieves high-level gene expression: human growth hormone production

Kozak

Kabat²

1990

J Virol

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Retroviral vectors offer major advantages for gene transfer studies but have not been useful for producing proteins in large quantities. This deficiency has resulted in part from interference to superinfection, which limits the numbers of active proviruses in cells. Recently, we found that these vectors amplify when they are added as calcium phosphate precipitates to cocultures of cells that package retroviruses into ecotropic and amphotropic host range envelopes. Helper-free virions from either cell type can infect the other without interference, resulting in theoretically limitless back-and-forth (ping-pong) vector replication. In initial studies, however, amplifications of a vector that contained the human growth hormone gene ceased when the hormone produced was 0.3% or less of cellular protein synthesis. This limit was caused by two factors. First, recombinant shutoff viruses that are replication defective and encode envelope glycoproteins form at a low probability during any round of the vector replication cycle and these spread in cocultures, thereby establishing interference. Single cells in shutoff cocultures therefore synthesize both ecotropic and amphotropic envelope glycoproteins, and they release promiscuous (presumably hybrid) virions. The probability of forming shutoff viruses before the vector had amplified to a high multiplicity was reduced by using small cocultures. Second, cells with large numbers of proviruses are unhealthy and their proviral expression can be unstable. Stable expresser cell clones were obtained by selection. Thereby, cell lines were readily obtained that stably produce human growth hormone as 4 to 6% of the total protein synthesis. A ping-pong retroviral vector can be used for high-level protein production in vertebrate cells.

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“…It is possible that the generation of FeLV-B is just one of the ways in which FeLV can overcome the interference barrier created by a resident FeLV-A provirus, thereby allowing a further hit of viral integration to occur in a developing neoplastic clone. Since there are other ways in which this barrier might be overcome (1,37), and FeLV-B envelope proteins could conceivably help to deliver a non-FeLV-B genome by pseudotype formation (17), the frequent but not universal detection of FeLV-B in tumor DNA could thus be explained. Also, the introduction of an activated myc gene with the FeLV-myc viruses would reduce by at least one the number of insertions required to complete the transformation process, further relieving the requirement for FeLV-B.…”

Section: Discussionmentioning

confidence: 99%

Genetic determinants of feline leukemia virus-induced lymphoid tumors: patterns of proviral insertion and gene rearrangement

Tsatsanis

Fulton

Nishigaki

et al. 1994

J Virol

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The genetic basis of feline leukemia virus (FeLV)-induced lymphoma was investigated in a series of 63 lymphoid tumors and tumor cell lines of presumptive T-cell origin. These were examined for virus-induced rearrangements of the c-myc,flvi-2 (bmi-1),fit-1, and pim-1 loci, for T-cell receptor (TCR) gene rearrangements, and for the presence of env recombinant FeLV (FeLV-B). The myc locus was most frequently affected in naturally occurring lymphomas (32%; n = 38) either by transduction (21%) or by proviral insertion (11%). Proviral insertions were also common atflvi-2 (24%). The two other loci were occupied in a smaller number of the naturally occurring tumors (fit-i, 8%; pim-i, 5%). Examination of the entire set of tumors showed that significant numbers were affected at two (19%Yo) or three (5%) of the loci. Occupation of the fit-i locus was observed most frequently in tumors induced by FeLV-myc strains, whileflvi-2 insertions occurred with similar frequency in the presence or absence of obvious c-myc activation. These results suggest a hierarchy of mutational events in the genesis of feline T-cell lymphomas by FeLV and implicate insertion atfit-i as a late progression step. The strongest links observed were with T-cell development, as monitored by rearrangement status of the TCR n-chain gene, which was positively associated with activation of myc (P < 0.001), and with proviral insertion at flvi-2 (P = 0.02). This analysis also revealed a genetically distinct subset of thymic lymphomas with unrearranged TCR ,8-chain genes in which the known target loci were involved very infrequently. The presence of env recombinant FeLV (FeLV-B) showed a negative correlation with proviral insertion at fit-i, possibly due to the rapid onset of these tumors. These results shed further light on the multistep process of FeLV leukemogenesis and the relationships between lymphoid cell maturation and susceptibility to FeLV transformation.

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Frequent hereditable shutdown of murine retrovirus gene expression in murine cell lines.

Cited by 11 publications

References 39 publications

Host Genetic Control of Spontaneous and Induced Immunity to Friend Murine Retrovirus Infection

Host Genetic Control of Spontaneous and Induced Immunity to Friend Murine Retrovirus Infection

Ping-pong amplification of a retroviral vector achieves high-level gene expression: human growth hormone production

Genetic determinants of feline leukemia virus-induced lymphoid tumors: patterns of proviral insertion and gene rearrangement

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