Human immunodeficiency virus type 1 Vpr arrests the cell cycle in G2 by inhibiting the activation of p34cdc2-cyclin B

Re, Fabio; Braaten, Douglas; Franke, E K; Luban, Jeremy

doi:10.1128/jvi.69.11.6859-6864.1995

Cited by 358 publications

(167 citation statements)

References 40 publications

(41 reference statements)

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“…However, when actin is in limiting amounts, a contractile ring will not completely form, preventing cytokinesis (1). Interestingly, HIV-1 viral protein R (Vpr) expression arrests the cell cycle in G 2 (27,48) and induces the formation of aberrant multipolar spindles as a result of abnormal centrosome duplication with a subsequent inhibition of cytokinesis (63). These observations are morphologically similar to those in cells expressing IBV N protein or in IBV-infected primary cells (Fig.…”

Section: Discussionmentioning

confidence: 62%

Interaction of the Coronavirus Nucleoprotein with Nucleolar Antigens and the Host Cell

Chen

Wurm

Britton³

et al. 2002

J Virol

126

148

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Coronavirus nucleoproteins (N proteins) Infectious bronchitis virus (IBV), a member of the Coronavirus genus of the Coronaviridae family, order Nidovirales (13), is an enveloped virus with a single-stranded, positive-sense RNA genome of 27,608 nucleotides (9) that is 5Ј capped and 3Ј polyadenylated which replicates in the cytoplasm of infected cells. The 5Ј two-thirds of the IBV genome encodes the replicase-transcription complex, Rep1a and Rep1ab, the latter resulting from a Ϫ1 frameshift (10). During IBV replication, a 3Ј-coterminal nested set of six subgenomic mRNAs are synthesized that encode other viral proteins, including nucleoprotein (N protein). Recently, we have reported that IBV N protein localizes to the cytoplasm and a structure in the nucleus proposed to be the nucleolus both in IBV-infected cells and in cells transfected with a plasmid expressing IBV N protein under the control of a PolII promoter (26), a result subsequently confirmed in species-specific and -nonspecific cells expressing the mouse hepatitis virus (MHV) and porcine transmissible gastroenteritis virus (TGEV) N proteins (64).The nucleolus is only present during interphase in mammalian cells (1) and is formed around ribosomal DNA repeats, which cluster at chromosomal loci called nucleolar organizer regions. It is the site where 5.8S, 18S, and 28S rRNAs are transcribed, processed, and assembled into ribosome subunits (11, 51). The nucleolus also sequesters regulatory complexes and has been implicated in the regulation of the cell cycle, telomerase activity, signal recognition particle biogenesis, small RNA processing, and mRNA transport (40, 41). The nucleolus is a dynamic structure composed of (or contains) at least 271 proteins (4), including nucleolin, fibrillarin, spectrin, B23, and the ribosomal proteins S5 and L9 (12, 51). Nucleolin (also called C23) represents 10% of the total nucleolar protein content, is highly phosphorylated and methylated, and also can be ADP-ribosylated (21). One of the main functions of nucleolin is processing the first cleavage step of rRNA in the presence of U3 snoRNP (21). Nucleolin may also function as a chaperone for correct folding in pre-rRNA processing (2). Fibrillarin is highly conserved in sequence, structure, and function in eukaryotes (5) and is directly involved in many posttranscriptional processes, including pre-rRNA processing, pre-rRNA methylation, and ribosome assembly (60).As a consequence of infection, a number of viral proteins interact with the nucleolus and can reorganize nucleolar antigens (25), with examples from retroviruses, DNA viruses, and RNA viruses. These include human immunodeficiency virus type 1 (HIV-1) Rev (16) and tat (56), Newcastle disease virus matrix protein (42), adenovirus IVa2 gene product (37) and V protein (39), Marek's disease virus MEQ protein (36), hepatitis D virus large-delta antigen (54), and porcine reproductive and respiratory syndrome virus nucleocapsid protein (49). The nucleolus is also the site of Borna disease virus replication and transcription (47...

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Section: Discussionmentioning

confidence: 62%

Interaction of the Coronavirus Nucleoprotein with Nucleolar Antigens and the Host Cell

Chen

Wurm

Britton³

et al. 2002

J Virol

126

148

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“…It is not unusual for viruses and viral proteins to interact with the cell cycle machinery to promote virus replication; this is a common feature of DNA viruses that replicate in the nucleus (44). Retroviruses also disrupt the cell cycle; thus, human immunodeficiency virus type 1 Vpr arrests cells in the G 2 phase (24), resulting in an increase in virus production (51). Altering the host cell cycle appears to be less common in RNA viruses and has not been extensively described in the literature.…”

Section: Discussionmentioning

confidence: 99%

Localization to the Nucleolus Is a Common Feature of Coronavirus Nucleoproteins, and the Protein May Disrupt Host Cell Division

Wurm¹,

Chen²,

Hodgson³

et al. 2001

J Virol

207

238

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The subcellular localization of transmissible gastroenteritis virus (TGEV) and mouse hepatitis virus (MHV) (group I and group II coronaviruses, respectively) nucleoproteins (N proteins) were examined by confocal microscopy. The proteins were shown to localize either to the cytoplasm alone or to the cytoplasm and a structure in the nucleus. This feature was confirmed to be the nucleolus by using specific antibodies to nucleolin, a major component of the nucleolus, and by confocal microscopy to image sections through a cell expressing N protein. These findings are consistent with our previous report for infectious bronchitis virus Coronaviruses are enveloped RNA viruses with nonsegmented, single-stranded, positive-sense RNA genomes of 27 to 32 kb that are 5Ј capped and 3Ј polyadenylated (26). The 5Ј two-thirds of the coronavirus genome encodes the virus contribution to the replicase-transcription complex, Rep1a and Rep1b, the latter resulting from a Ϫ1 frameshift (8). During coronavirus replication, a 3Ј-coterminal nested set of subgenomic mRNAs, which encode other viral proteins, including nucleoprotein (N protein), are synthesized. In part, based on similar genome replication strategies (17, 61), the coronavirus family, Coronaviridae, has been grouped together with the arterivirus family, Arteriviridae, into the order Nidovirales (11). While gene functions and distributions for the two families are similar, there are some differences that might lead to subtle differences in replication strategies. Recently, we have reported that the coronavirus infectious bronchitis virus (IBV) N protein localizes to the cytoplasm and a structure in the nucleus proposed to be the nucleolus in both IBV-infected cells and cells transfected with a plasmid expressing IBV N protein under the control of a PolII promoter (23). A similar result was reported with the arterivirus porcine reproductive and respiratory syndrome virus (PRRSV) N protein (54), suggesting that localization of N protein to the nucleolus was probably common to these two virus families and potentially common to all Nidovirales.Coronavirus replication is generally accepted to occur in the cytoplasm of infected cells (66), although for IBV an intact cell nucleus has been proposed to be necessary for virus replication (20). In addition, proteins normally associated with the nucleus have been implicated in the replication of the murine coronavirus mouse hepatitis virus (MHV) (30). The nucleolus is a structure found within the nucleus and is only present during interphase (1). It is the site where rRNA is synthesized and where biogenesis of ribosomal subunits and polymerase III transcripts occurs (10, 57). The nucleolus also sequesters regulatory complexes and has been implicated in the regulation of the cell cycle (10). The possible involvement of the nucleolus in coronavirus replication is not exclusive to coronaviruses. As a consequence of infection or a deliberate process, a number of viruses, including adenoviruses (37) and poliovirus (65), redistribute nucleolin, ...

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“…Although in the last 10 years, well over 20 papers, from a variety of laboratories have been published on the subject, the exact mechanism(s) remains unclear. The Cdk1/ cyclin B1 complex is clearly inactive in Vpr-arrested cells (He et al, 1995;Re et al, 1995), but more contentious are the upstream pathways that lead to this inhibition. The mechanisms that have been proposed to explain how Vpr expression may contribute to G2/M arrest include (1) Vpr binding to chromatin and/or splicing factors, which causes activation of ATR, and leads eventually to changes in the activity of the Wee1 kinase and/or the Cdc25 phosphatase (Lai et al, 2005;Terada and Yasuda, 2006); and the less well characterized phenomena of (2) direct binding to Cdc25C and inhibition of its phosphatase activity (Goh et al, 2004); (3) alteration of the level of Wee1 protein (Yuan et al, 2004); (4) effects on PP2A (Elder et al, 2001); (5) activation of the p21 promoter and p21-mediated Cdk1/cyclin B inhibition (Chowdhury et al, 2003); and (6) downregulation of expression of genes in the MAPK pathway (Yoshizuka et al, 2005) (see Fig.…”

Section: Inhibition Of Mitotic Exitmentioning

confidence: 99%

G2/M cell cycle arrest in the life cycle of viruses

Davy¹,

Doorbar²

2007

Virology

130

133

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There is increasing evidence that viral infection, expression of viral protein or the presence of viral DNA causes the host cell cycle to arrest during G2/M. The mechanisms used by viruses to cause arrest vary widely; some involve the activation of the cellular pathways that induce arrest in response to DNA damage, while others use completely novel means. The analysis of virus-mediated arrest has not been proven easy, and in most cases the consequences of arrest for the virus life cycle are not well defined. However, a number of effects of arrest are being investigated and it will be interesting to see to what extent perturbation of the G2/M transition is involved in viral infections.

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Human immunodeficiency virus type 1 Vpr arrests the cell cycle in G2 by inhibiting the activation of p34cdc2-cyclin B

Cited by 358 publications

References 40 publications

Interaction of the Coronavirus Nucleoprotein with Nucleolar Antigens and the Host Cell

Interaction of the Coronavirus Nucleoprotein with Nucleolar Antigens and the Host Cell

Localization to the Nucleolus Is a Common Feature of Coronavirus Nucleoproteins, and the Protein May Disrupt Host Cell Division

G2/M cell cycle arrest in the life cycle of viruses

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