Activation of human immunodeficiency virus type 1 by DNA damage in human cells

Nature ◽  
1988 ◽  
Vol 333 (6168) ◽  
pp. 78-81 ◽  
Author(s):  
Kristoffer Valerie ◽  
Anne Delers ◽  
Claudine Bruck ◽  
Clotilde Thiriart ◽  
Hagai Rosenberg ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Dna Damage ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Human Cells ◽  
Immunodeficiency Virus

scholarly journals DNA Damage Sensors ATM, ATR, DNA-PKcs, and PARP-1 Are Dispensable for Human Immunodeficiency Virus Type 1 Integration

2005 ◽  
Vol 79 (5) ◽  
pp. 2973-2978 ◽  
Author(s):  
Yasuo Ariumi ◽  
Priscilla Turelli ◽  
Mitsuko Masutani ◽  
Didier Trono
Keyword(s):  
Human Immunodeficiency Virus ◽  
Dna Damage ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Human Cells ◽  
Target Cells ◽  
Immunodeficiency Virus ◽  
Parp 1 ◽  
Hiv 1

ABSTRACT Integration of a DNA copy of the viral RNA genome is a crucial step in the life cycle of human immunodeficiency virus type 1 (HIV-1) and other retroviruses. While the virally encoded integrase is key to this process, cellular factors yet to be characterized are suspected to participate in its completion. DNA damage sensors such as ATM (ataxia-telangiectasia mutated), ATR (ATM- and Rad3-related), DNA-PK (DNA-dependent protein kinase), and PARP-1 [poly(ADP-ribose) polymerase 1] play central roles in responses to various forms of DNA injury and as such could facilitate HIV integration. To test this hypothesis, we examined the susceptibility to infection with wild-type HIV-1 and to transduction with a vesicular stomatitis virus G protein (VSV-G)-pseudotyped HIV-1-derived lentiviral vector of human cells stably expressing small interfering RNAs against ATM, ATR, and PARP-1. We found that integration normally occurred in these knockdown cells. Similarly, the VSV-G-pseudotyped HIV-1-based vector could effectively transduce ATM and PARP-1 knockout mouse cells as well as human cells deficient for DNA-PK. Finally, treatment of target cells with the ATM and ATR inhibitors caffeine and wortmannin was without effect in these infectivity assays. We conclude that the DNA repair enzymes ATM, ATR, DNA-PKcs, and PARP-1 are not essential for HIV-1 integration.

scholarly journals UV-induced DNA damage is an intermediate step in UV-induced expression of human immunodeficiency virus type 1, collagenase, c-fos, and metallothionein.

1989 ◽  
Vol 9 (11) ◽  
pp. 5169-5181 ◽  
Author(s):  
B Stein ◽  
H J Rahmsdorf ◽  
A Steffen ◽  
M Litfin ◽  
P Herrlich
Keyword(s):  
Human Immunodeficiency Virus ◽  
Dna Damage ◽  
Uv Radiation ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Sequence Motif ◽  
Nf Kappa B ◽  
Immunodeficiency Virus ◽  
Hiv 1

UV irradiation of human and murine cells enhances the transcription of several genes. Here we report on the primary target of relevant UV absorption, on pathways leading to gene activation, and on the elements receiving the UV-induced signal in the human immunodeficiency virus type 1 (HIV-1) long terminal repeat, in the gene coding for collagenase, and in the cellular oncogene fos. In order to induce the expression of genes. UV radiation needs to be absorbed by DNA and to cause DNA damage of the kind that cannot be repaired by cells from patients with xeroderma pigmentosum group A. UV-induced activation of the three genes is mediated by the major enhancer elements (located between nucleotide positions -105 and -79 of HIV-1, between positions -72 and -65 of the collagenase gene, and between positions -320 and -299 of fos). These elements share no apparent sequence motif and bind different trans-acting proteins; a member of the NF kappa B family binds to the HIV-1 enhancer, the heterodimer of Jun and Fos (AP-1) binds to the collagenase enhancer, and the serum response factors p67 and p62 bind to fos. DNA-binding activities of the factors recognizing the HIV-1 and collagenase enhancers are augmented in extracts from UV-treated cells. The increase in activity is due to posttranslational modification. While AP-1 resides in the nucleus and must be modulated there, NF kappa B is activated in the cytoplasm, indicating the existence of a cytoplasmic signal transduction pathway triggered by UV-induced DNA damage. In addition to activation, new synthesis of AP-1 is induced by UV radiation.

scholarly journals Polyubiquitination of APOBEC3G Is Essential for Its Degradation by HIV-1 Vif

2010 ◽  
Vol 84 (9) ◽  
pp. 4840-4844 ◽  
Author(s):  
Qiujia Shao ◽  
Yudi Wang ◽  
James E. K. Hildreth ◽  
Bindong Liu
Keyword(s):  
Human Immunodeficiency Virus ◽  
Simian Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Proteasomal Degradation ◽  
Human Cells ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Proteasomal degradation of APOBEC3G is a critical step for human immunodeficiency virus type 1 (HIV-1) replication. However, the necessity for polyubiquitination of APOBEC3G in this process is still controversial. In this study, we showed that although macaque simian immunodeficiency virus (SIVmac) Vif is more stable than HIV-1 Vif in human cells, SIVmac Vif induces degradation of APBOEC3G as efficiently as HIV-1 Vif. Overexpression of APOBEC3G or lysine-free APOBEC3G stabilized HIV-1 Vif, indicating that APOBEC3G degradation is independent of the degradation of Vif. Furthermore, an in vivo polyubiquitination assay showed that lysine-free APOBEC3G was also polyubiquitinated. These data suggest that polyubiquitination of APOBEC3G, not that of HIV-1 Vif, is crucial for APOBEC3G degradation.

scholarly journals Cyclophilin A and TRIM5α Independently Regulate Human Immunodeficiency Virus Type 1 Infectivity in Human Cells

2006 ◽  
Vol 80 (6) ◽  
pp. 2855-2862 ◽  
Author(s):  
Elena Sokolskaja ◽  
Lionel Berthoux ◽  
Jeremy Luban
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiviral Activity ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Leukemia Virus ◽  
Cyclophilin A ◽  
Human Cells ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Cyclophilin A (CypA), a cytoplasmic, human immunodeficiency virus type 1 (HIV-1) CA-binding protein, acts after virion membrane fusion with human cells to increase HIV-1 infectivity. HIV-1 CA is similarly greeted by CypA soon after entry into rhesus macaque or African green monkey cells, where, paradoxically, the interaction decreases HIV-1 infectivity by facilitating TRIM5α-mediated restriction. These observations conjure a model in which CA recognition by the human TRIM5α orthologue is precluded by CypA. Consistent with the model, selection of a human cell line for decreased restriction of the TRIM5α-sensitive, N-tropic murine leukemia virus (N-MLV) rendered HIV-1 transduction of these cells independent of CypA. Additionally, HIV-1 virus-like particles (VLPs) saturate N-MLV restriction activity, particularly when the CA-CypA interaction is disrupted. Here the effects of CypA and TRIM5α on HIV-1 restriction were examined directly. RNA interference was used to show that endogenous human TRIM5α does indeed restrict HIV-1, but the magnitude of this antiviral activity was not altered by disruption of the CA-CypA interaction or by elimination of CypA protein. Conversely, the stimulatory effect of CypA on HIV-1 infectivity was completely independent of human TRIM5α. Together with previous reports, these data suggest that CypA protects HIV-1 from an unknown antiviral activity in human cells. Additionally, target cell permissivity increased after loading with heterologous VLPs, consistent with a common saturable target that is epistatic to both TRIM5α and the putative CypA-regulated restriction factor.

scholarly journals The human immunodeficiency virus type 1 Vpr protein upregulates PVR via activation of the ATR-mediated DNA damage response pathway

2013 ◽  
Vol 94 (12) ◽  
pp. 2664-2669 ◽  
Author(s):  
Lia Vassena ◽  
Erica Giuliani ◽  
Giulia Matusali ◽  
Éric A. Cohen ◽  
Margherita Doria
Keyword(s):  
Human Immunodeficiency Virus ◽  
Dna Damage ◽  
Cell Surface ◽  
Dna Damage Response ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Immunodeficiency Virus ◽  
Damage Response ◽  
Dna Damage Response Pathway

Viral infection may induce the cell-surface expression of PVR (CD155) that, upon recognition by its cognate activating DNAM-1 receptor present on cytotoxic lymphocytes, may promote antiviral immune responses. Here we show that expression of the human immunodeficiency virus type 1 (HIV-1) Vpr protein in Jurkat T cells increases cell-surface and total PVR levels. Analysis of mutated Vpr variants indicated that Vpr uses the same protein surfaces, and hence probably the same mechanisms, to upregulate PVR and arrest the cell cycle in the G2 phase. Moreover, we found that PVR upregulation by Vpr relied on the ability of the protein to activate the ATR kinase that triggers the DNA damage response pathway and G2 arrest. Finally, we showed that Vpr contributes to PVR up-modulation in HIV-infected CD4+ T lymphocytes and inhibits the PVR downregulating activity of the viral Nef protein.

scholarly journals Potent and Specific Inhibition of Human Immunodeficiency Virus Type 1 Replication by RNA Interference

2002 ◽  
Vol 76 (18) ◽  
pp. 9225-9231 ◽  
Author(s):  
Glen A. Coburn ◽  
Bryan R. Cullen
Keyword(s):  
Human Immunodeficiency Virus ◽  
Rna Interference ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Human Cells ◽  
Mrna Targets ◽  
Human T Cell ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Synthetic small interfering RNAs (siRNAs) have been shown to induce the degradation of specific mRNA targets in human cells by inducing RNA interference (RNAi). Here, we demonstrate that siRNA duplexes targeted against the essential Tat and Rev regulatory proteins encoded by human immunodeficiency virus type 1 (HIV-1) can specifically block Tat and Rev expression and function. More importantly, we show that these same siRNAs can effectively inhibit HIV-1 gene expression and replication in cell cultures, including those of human T-cell lines and primary lymphocytes. These observations demonstrate that RNAi can effectively block virus replication in human cells and raise the possibility that RNAi could provide an important innate protective response, particularly against viruses that express double-stranded RNAs as part of their replication cycle.

Sign in / Sign up

Export Citation Format

Share Document