Rous sarcoma virus infection of synchronized cells establishes provirus integration during S-phase DNA synthesis prior to cellular division.

Humphries, E H; Glover, Caroline; Reichmann, M. E.

doi:10.1073/pnas.78.4.2601

Cited by 51 publications

(39 citation statements)

References 16 publications

(15 reference statements)

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“…Recent studies in cycling cells have demonstrated that HIV-1 DNA can enter the nucleus and become integrated prior to mitosis [Katz et al, 2003] suggesting that the NPC pathway is used in cycling cells. Similar findings with ASV [Katz et al, 2003] are consistent with earlier studies [Humphries et al, 1981]. Although these investigations did not rule out the use of a mitotic pathway, they showed quite clearly that mitosisindependent nuclear import is a prominent pathway for both viruses in cycling cells.…”

Section: Nuclear Entrysupporting

confidence: 91%

“…The discovery that HIV-1 could complete early events in some non-cycling cells and that HIV-1 DNA could enter the nucleus through the NPC [Weinberg et al, 1991;Bukrinsky et al, 1992], appeared to distinguish HIV-1 from the prototype ''oncoretrovirus,'' MLV, which required mitosis. However, recent studies with ASV have demonstrated its capacity for mitosis-independent integration [Hatziioannou and Goff, 2001;Katz et al, 2002Katz et al, , 2003Greger et al, 2004], consistent with the earlier findings [Humphries et al, 1981]. Thus, mitosis-independent integration of viral DNA in non-cycling cells is not limited to HIV and lentiviruses.…”

Section: Historical Perspectives and Dogmasupporting

confidence: 86%

“…It was later shown that cells arrested by serum starvation (G 0 ) could not support completion of the reverse transcription step [Fritsch and Temin, 1977]. Further studies by Humphries [Humphries et al, 1981] demonstrated that if cells were infected with ASV at the time of release from serum starvation (G 0 ), reverse transcription could be completed and integration could occur prior to mitosis. Results from these studies suggested that passage through mitosis was only required to ''activate'' the newly integrated DNA for virus production [Humphries et al, 1981].…”

Section: Historical Perspectives and Dogmamentioning

confidence: 99%

“…Further studies by Humphries [Humphries et al, 1981] demonstrated that if cells were infected with ASV at the time of release from serum starvation (G 0 ), reverse transcription could be completed and integration could occur prior to mitosis. Results from these studies suggested that passage through mitosis was only required to ''activate'' the newly integrated DNA for virus production [Humphries et al, 1981]. These findings were consistent with earlier studies by Varmus and co-workers, who also concluded that ASV DNA could be integrated prior to mitosis [Varmus et al, 1977].…”

Section: Historical Perspectives and Dogmamentioning

confidence: 99%

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Effects of cell cycle status on early events in retroviral replication

Katz

Greger

Skalka

2005

J of Cellular Biochemistry

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The study of retroviruses over the last century has revealed a wide variety of disease-producing mechanisms, as well as apparently harmless interactions with animal hosts. Despite their potential pathogenic properties, the intrinsic features of retroviruses have been harnessed to create gene transfer vectors that may be useful for the treatment of disease. Retroviruses, as all viruses, have evolved to infect specific cells within the host, and such specificities are relevant to both pathogenesis and retrovirus-based vector design. The majority of cells of an animal host are not progressing rapidly through the cell cycle, and such a cellular environment appears to be suboptimal for replication of all retroviruses. Retrovirus-based vectors can therefore be restricted in many important target cells, such as post-mitotic differentiated cells or stem cells that may divide only infrequently. Despite intense interest, our understanding of how cell cycle status influences retroviral infection is still quite limited. In this review, we focus on the importance of the cell cycle as it relates to the early steps in retroviral replication. Retroviruses have been categorized based on their abilities to complete these early steps in non-cycling cells. However, all retroviruses are subject to a variety of cell cycle restrictions. Here, we discuss such restrictions, and how they may block retroviral replication, be tolerated, or overcome. J. Cell. Biochem. 94: 880-889, 2005. ß 2005 Wiley-Liss, Inc.

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Section: Nuclear Entrysupporting

confidence: 91%

Section: Historical Perspectives and Dogmasupporting

confidence: 86%

Section: Historical Perspectives and Dogmamentioning

confidence: 99%

Section: Historical Perspectives and Dogmamentioning

confidence: 99%

See 2 more Smart Citations

Effects of cell cycle status on early events in retroviral replication

Katz

Greger

Skalka

2005

J of Cellular Biochemistry

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“…During this process cellular transformation takes place owing to the expression of v-src protein (Brugge & Erikson, 1977). Of these steps, integration of viral DNA is believed to be dependent on synthesis of host DNA (Varmus et al, 1977(Varmus et al, , 1979Humphries et al, 1981). Since the above events supposedly take place sequentially, all the steps after DNA integration are thought not to occur if this step is blocked.…”

Section: Introductionmentioning

confidence: 99%

Infection of terminally differentiated myotubes with Rous sarcoma virus (RSV): lack of DNA integration but presence of RSV mRNA

Tanaka¹,

Hara

Park

et al. 1992

Journal of General Virology

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We re-examined the generally accepted concept that replication of Rous sarcoma virus (RSV) requires host DNA synthesis. We used terminally differentiated chicken myotubes as the host because chromosomal DNA replication is completely abolished by the natural differentiation process. Southern blot analysis detected unintegrated viral DNA in both the nucleus and cytoplasm of infected myotubes. This indicated that reverse transcription of the infecting viral RNA and transport of the newly synthesized viral DNA into the nucleus proceeded normally in myotubes. However, restriction enzyme digestion of high Mr DNA prepared from infected myotubes produced none of the fragments specific for RSV, indicating that the viral DNA had failed to integrate into the myotube chromosomal DNA. In these infected myotubes, viral RNA was detected by in situ hybridization. Northern blot analysis showed the presence of all three RSV mRNAs (38S, 28S and 21S). The amount of these viral RNAs in infected myotubes was comparable with that found in infected fibroblasts. We conclude that host DNA synthesis is required for RSV integration, but, in contrast to the generally accepted concept, viral DNA integration is not an absolute requirement for transcription of the RSV genome.

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Clonal heterogeneity in the early embryonic rodent cortical germinal zone and the separation of subventricular from ventricular zone lineages

1997

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The cell cycle kinetics of individual clones of cells in the embryonic cortex were studied to determine the amount of heterogeneity among cortical progenitors. This kinetic heterogeneity may be the first sign of heterogeneous differentiation in the proliferating cortical germinal zone. Retroviral lineage tracing of clonal progeny in the embryonic day 16 (E16) rat cortex (48 hr after the retroviral infection and [3H]thymidine labeling of proliferating cells) permitted a description of the formation of the preplate in the medial cortex and the formation of the subventricular zone (SVZ) in the lateral cortex. Forty percent of the retrovirally tagged clones were double‐labeled with a pulse of [3H]thymidine, corresponding to the 40% of ventricular zone cells in S‐phase at the time of [3H]thymidine injection. Most of clones had cell numbers with powers of 2 (2, 4, and 8 cells), suggesting synchronous modes of division. Nevertheless, 15% of the retrovirally tagged clones that were double‐labeled with [3H]thymidine at the time of [3H]thymidine injection showed asynchronous mode of division. Clonally related cells in the ventricular zone showed considerable variability in cell cycle times: 56% of the clones (8‐cell clones) were composed of faster cycling cells with cell cycle times of 12 hr, and 25% of the clones (4‐cell clones) represented slower cycling cells with cell cycle times of 16 hr. The clones migrating outside the ventricular zone differed in size and spatial distribution in the lateral versus medial cortex. In the lateral cortex, half the migrating clones were large proliferating 8‐cell clones with all their members contained within the forming SVZ. In the medial cortex, the majority of the migrating clones were 2‐cell and 4‐cell clones. Given that the medial cortex matures later than the lateral neocortex and that no SVZ has formed in the rat medial cortex by E16, we suggest that the majority of cells that leave the medial cortical VZ by E16 are cells destined to form the neuronal populations of the preplate. The early embryonic cortical ventricular zone includes a mosaic of specialized progenitor cells. Dev. Dyn. 1997;210:328–343. © 1997 Wiley‐Liss, Inc.

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Rous sarcoma virus infection of synchronized cells establishes provirus integration during S-phase DNA synthesis prior to cellular division.

Cited by 51 publications

References 16 publications

Effects of cell cycle status on early events in retroviral replication

Effects of cell cycle status on early events in retroviral replication

Infection of terminally differentiated myotubes with Rous sarcoma virus (RSV): lack of DNA integration but presence of RSV mRNA

Clonal heterogeneity in the early embryonic rodent cortical germinal zone and the separation of subventricular from ventricular zone lineages

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