Research Topics
Genomes and GenesSpecies | Warner GreeneSummaryAffiliation: University of California Country: USA Publications
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Publications
Semen-mediated enhancement of HIV infection is donor-dependent and correlates with the levels of SEVIKyeong Ae Kim
Institute of Molecular Virology, University Hospital Ulm, 89081 Ulm, Germany
Retrovirology 7:55. 2010..Despite its importance for the global spread of HIV-1, however, the effect of semen on virus infection is controversial...
Primary T-cells from human CD4/CCR5-transgenic rats support all early steps of HIV-1 replication including integration, but display impaired viral gene expressionChristine Goffinet
Department of Virology, University of Heidelberg, Heidelberg, Germany
Retrovirology 4:53. 2007....
Human cyclin T1 expression ameliorates a T-cell-specific transcriptional limitation for HIV in transgenic rats, but is not sufficient for a spreading infection of prototypic R5 HIV-1 strains ex vivoNico Michel
Department of Virology, University of Heidelberg, 69120 Heidelberg, Germany
Retrovirology 6:2. 2009..Rat primary CD4 T-cells, but not macrophages, display a profound transcriptional deficit that is ameliorated by transient trans-complementation with the human Tat-interacting protein Cyclin T1 (hCycT1)...
A history of AIDS: looking back to see aheadWarner C Greene
Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA 94158, USA
Eur J Immunol 37:S94-102. 2007..With these sobering statistics as a backdrop, this feature traces the history of the devastating HIV/AIDS pandemic and offers a view for what the future may hold...
Charting HIV's remarkable voyage through the cell: Basic science as a passport to future therapyWarner C Greene
Gladstone Institute of Virology and Immunology, Department of Medicine, University of California at San Francisco, San Francisco, California, USA
Nat Med 8:673-80. 2002..Understanding the dynamic interplay of host cell and virus is essential to the effort to eradicate HIV...
The brightening future of HIV therapeuticsWarner C Greene
Gladstone Institute of Virology and Immunology, Department of Medicine, University of California, San Francisco, California 94141-9100, USA
Nat Immunol 5:867-71. 2004
Cellular APOBEC3G restricts HIV-1 infection in resting CD4+ T cellsYa Lin Chiu
Gladstone Institute of Virology and Immunology, University of California, San Francisco, California 94143, USA
Nature 435:108-14. 2005..the reverse transcripts slowly formed in unstimulated CD4+ T cells reveals only low levels of dG dA hypermutation, raising the possibility that the APOBEC3G-restricting activity may not be strictly dependent on deoxycytidine deamination..
Slipping through the door: HIV entry into the nucleusMichael P Sherman
Gladstone Institute of Virology and Immunology, P O Box 419100, San Francisco, CA 94141 9100, USA
Microbes Infect 4:67-73. 2002..We discuss recent studies that have advanced our understanding of this key step in the HIV life cycle...
Newly synthesized APOBEC3G is incorporated into HIV virions, inhibited by HIV RNA, and subsequently activated by RNase HVanessa B Soros
Gladstone Institute of Virology and Immunology, San Francisco, California, United States of America
PLoS Pathog 3:e15. 2007..These findings highlight an unexpected interplay between host and virus where initiation of antiviral enzymatic activity is dependent on the action of an essential viral enzyme...
NF-kappaB RelA phosphorylation regulates RelA acetylationLin Feng Chen
Gladstone Institute of Virology and Immunology, 1650 Owens St, San Francisco, CA 94158, USA
Mol Cell Biol 25:7966-75. 2005..These findings indicate that the acetylation of RelA at lysine 310 is importantly regulated by prior phosphorylation of serines 276 and 536. Such phosphorylated and acetylated forms of RelA display enhanced transcriptional activity...
HIV-1 Vif blocks the antiviral activity of APOBEC3G by impairing both its translation and intracellular stabilityKim Stopak
Gladstone Institute of Virology and Immunology, University of California-San Francisco, San Francisco, CA 94143, USA
Mol Cell 12:591-601. 2003....
The APOBEC3 cytidine deaminases: an innate defensive network opposing exogenous retroviruses and endogenous retroelementsYa Lin Chiu
Gladstone Institute of Virology and Immunology, San Francisco, California 94158, USA
Annu Rev Immunol 26:317-53. 2008....
A seminal finding for understanding HIV transmissionNadia R Roan
Gladstone Institute of Virology and Immunology, University of California, San Francisco, 1650 Owens Street, San Francisco, CA 94158, USA
Cell 131:1044-6. 2007..As a potential explanation for this discrepancy, Münch et al. (2007) now identify and characterize a factor found in human semen that under certain conditions can enhance HIV infectivity by more than 100,000-fold...
Measuring HIV fusion mediated by envelopes from primary viral isolatesMarielle Cavrois
Gladstone Institute of Virology and Immunology, San Francisco, CA 94158, USA
Methods 53:34-8. 2011..Here, we describe a relatively simple strategy to clone primary envelopes into a provirus and increase the sensitivity of the virion-based fusion assay...
HIV is inactivated after transepithelial migration via adult oral epithelial cells but not fetal epithelial cellsSharof M Tugizov
Department of Medicine, University of California San Francisco, 513 Parnassus Ave, San Francisco, CA 94143 0512, USA
Virology 409:211-22. 2011..Inactivation of innate proteins in adult oral keratinocytes restored HIV infectivity. These data suggest that high-level innate protein expression may contribute to the resistance of the adult oral epithelium to HIV transmission...
Aminoquinoline surfen inhibits the action of SEVI (semen-derived enhancer of viral infection)Nadia R Roan
Gladstone Institute of Virology and Immunology, University of California, San Francisco, California 94158, USA
J Biol Chem 285:1861-9. 2010..Because SEVI can increase HIV infectivity by several orders of magnitude, supplementing current HIV microbicide candidates with SEVI inhibitors, such as surfen, might greatly increase their potency...
p53 induces NF-kappaB activation by an IkappaB kinase-independent mechanism involving phosphorylation of p65 by ribosomal S6 kinase 1Jan Bohuslav
Gladstone Institute of Virology and Immunology and the Department of Medicine, University of California, San Francisco, California 94143 1234, USA
J Biol Chem 279:26115-25. 2004..These findings highlight a rather unusual pathway of NF-kappaB activation, which is utilized by the p53 tumor suppressor...
Assessing acetylation of NF-kappaBLin-feng Chen
Gladstone Institute of Virology and Immunology, University of California, San Francisco 94158, USA
Methods 36:368-75. 2005..Anti-RelA antibodies that selectively react with site-specific acetylated forms of RelA are a singularly powerful tool for the study of NF-kappaB acetylation both in vivo and in vitro...
NF-kappaB p50 promotes HIV latency through HDAC recruitment and repression of transcriptional initiationSamuel A Williams
Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA 94158, USA
EMBO J 25:139-49. 2006..The combination of HDAC inhibitors and Tat merits consideration as a new strategy for purging latent HIV proviruses from their cellular reservoirs...
APOBEC3 cytidine deaminases: distinct antiviral actions along the retroviral life cycleYa-Lin Chiu
Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA 94141, USA
J Biol Chem 281:8309-12. 2006..Although scientifically fascinating, advances in APOBEC3 biology may lead to new antiviral drugs and improved lentiviral vectors for gene therapy...
Endogenous factors enhance HIV infection of tissue naive CD4 T cells by stimulating high molecular mass APOBEC3G complex formationJason F Kreisberg
Gladstone Institute of Virology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA
J Exp Med 203:865-70. 2006....
Multifaceted antiviral actions of APOBEC3 cytidine deaminasesYa Lin Chiu
Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA 94141 9100, USA
Trends Immunol 27:291-7. 2006....
High-molecular-mass APOBEC3G complexes restrict Alu retrotranspositionYa Lin Chiu
Gladstone Institute of Virology and Immunology, 1650 Owens Street, San Francisco, CA 94158, USA
Proc Natl Acad Sci U S A 103:15588-93. 2006....
Distinct patterns of cytokine regulation of APOBEC3G expression and activity in primary lymphocytes, macrophages, and dendritic cellsKim S Stopak
Gladstone Institute of Virology and Immunology, University of California, San Francisco, California 94158, USA
J Biol Chem 282:3539-46. 2007..Together, these results highlight the distinct inductive effects of select cytokines on A3G gene expression and A3G complex assembly that occur in natural cellular targets of HIV infection...
Novel targets for HIV therapyWarner C Greene
Gladstone Institute of Virology and Immunology, San Francisco, CA, USA
Antiviral Res 80:251-65. 2008....
The cationic properties of SEVI underlie its ability to enhance human immunodeficiency virus infectionNadia R Roan
Gladstone Institute of Virology and Immunology, University of California, P O Box 419100, San Francisco, CA 94141 9100, USA
J Virol 83:73-80. 2009..Combinations of agents that neutrale SEVI action and produce HIV virucidal effects are an attractive future direction for microbicide development...
APOBEC3G: an intracellular centurionYa Lin Chiu
Gladstone Institute of Virology and Immunology, San Francisco, CA 94158, USA
Philos Trans R Soc Lond B Biol Sci 364:689-703. 2009..LMM A3G opposes the external threat posed by exogenous retroviruses, while HMM A3G complexes oppose the internal threat posed by the retrotransposition of select types of retroelements...
Acetylation of RelA at discrete sites regulates distinct nuclear functions of NF-kappaBLin Feng Chen
Gladstone Institute of Virology and Immunology, University of California at San Francisco, San Francisco, CA 94141, USA
EMBO J 21:6539-48. 2002..Together, these findings highlight how site-specific acetylation of RelA differentially regulates distinct biological activities of the NF-kappaB transcription factor complex...
Protecting APOBEC3G: a potential new target for HIV drug discoveryKimberly Stopak
Gladstone Institute of Virology and Immunology, University of California, San Francisco, 1650 Owens Street, San Francisco, CA 9418, USA
Curr Opin Investig Drugs 6:141-7. 2005..The potent activity of APOBEC3G has led to considerable interest in the identification of small molecules that interrupt the Vif-induced degradative process...
Regulation of NF-kappaB action by reversible acetylationWarner C Greene
Gladstone Institute of Virology and Immunology, University of California, San Francisco, San Francisco, CA 94141, USA
Novartis Found Symp 259:208-17; discussion 218-25. 2004....
Shaping the nuclear action of NF-kappaBLin-feng Chen
Gladstone Institute of Virology and Immunology, University of California, San Francisco, California 94141, USA
Nat Rev Mol Cell Biol 5:392-401. 2004
Prostratin antagonizes HIV latency by activating NF-kappaBSamuel A Williams
Gladstone Institute of Virology and Immunology, University of California, San Francisco, San Francisco, California 94141, USA
J Biol Chem 279:42008-17. 2004..These findings provide new insights into the molecular pathway through which prostratin antagonizes HIV latency highlighting a central role for the action of NF-kappaB...
Abortive HIV infection mediates CD4 T cell depletion and inflammation in human lymphoid tissueGilad Doitsh
Gladstone Institute of Virology and Immunology, San Francisco, CA 94158, USA
Cell 143:789-801. 2010..While this response likely evolved to protect the host, it centrally contributes to the immunopathogenic effects of HIV...
Regulation of HIV-1 latency by T-cell activationSamuel A Williams
Gladstone Institute of Virology and Immunology, University of California, 1650 Owens Street, San Francisco, CA 94158, USA
Cytokine 39:63-74. 2007....
Human T-cell lymphotropic virus type 1 tax induction of biologically Active NF-kappaB requires IkappaB kinase-1-mediated phosphorylation of RelA/p65ALISON M O'MAHONY
Gladstone Institute for Virology and Immunology, Department of Medicine, University of California, San Francisco, California 94141, USA
J Biol Chem 279:18137-45. 2004..IKK2 plays a dominant role in signaling for IkappaBalpha degradation, whereas IKK1 appears to play an important role in enhancing the transcriptional activity of NF-kappaB by promoting RelA/p65 phosphorylation...
Compensatory link between fusion and endocytosis of human immunodeficiency virus type 1 in human CD4 T lymphocytesEvelyne Schaeffer
Gladstone Institute of Virology and Immunology, University of California, San Francisco, California 94141, USA
J Virol 78:1375-83. 2004..In summary, our results reveal an unexpected, CD4-mediated reciprocal relationship between the pathways governing HIV virion fusion and endocytosis...
Human immunodeficiency virus type 1 Tat protein inhibits the SIRT1 deacetylase and induces T cell hyperactivationHye Sook Kwon
Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA 94158, USA
Cell Host Microbe 3:158-67. 2008..These events likely contribute to the state of immune cell hyperactivation found in HIV-infected individuals...
The achilles heel of the trojan horse model of HIV-1 trans-infectionMarielle Cavrois
Gladstone Institute of Virology and Immunology, San Francisco, California, United States of America
PLoS Pathog 4:e1000051. 2008..This review traces the experimental lines of evidence that have contributed to what we view as the "rise and decline" of the Trojan horse model of HIV-1 trans-infection...
Regulation of distinct biological activities of the NF-kappaB transcription factor complex by acetylationLin-feng Chen
Gladstone Institute of Virology and Immunology, University of California, P.O. Box 419100, San Francisco, CA 94141-9100, USA
J Mol Med 81:549-57. 2003..This readies the cell for the next NF-kappaB-inducing stimulus. Thus, reversible acetylation of RelA serves as an important intranuclear regulatory mechanism that further provides for dynamic control of NF-kappaB action...
Nuclear export of Vpr is required for efficient replication of human immunodeficiency virus type 1 in tissue macrophagesMichael P Sherman
Gladstone Institute of Virology and Immunology, San Francisco, California 94141, USA
J Virol 77:7582-9. 2003....
Human immunodeficiency virus type 1 Nef-mediated downregulation of CD4 correlates with Nef enhancement of viral pathogenesisCheryl A Stoddart
Gladstone Institute of Virology and Immunology Departments of Medicine Microbiology and Immunology, University of California, San Francisco, California 94141, USA
J Virol 77:2124-33. 2003..Nef-mediated CD4 downregulation merits consideration as a new target for the development of small-molecule inhibitors...
Sustained induction of NF-kappa B is required for efficient expression of latent human immunodeficiency virus type 1Samuel A Williams
Gladstone Institute of Virology and Immunology, University of California San Francisco, 1650 Owens Street, San Francisco, CA 94158, USA
J Virol 81:6043-56. 2007..Conversely, the action of this phosphatase is overcome in the presence of Tat, promoting very efficient RNA Pol II elongation...
Human immunodeficiency virus fusion to dendritic cells declines as cells matureMarielle Cavrois
Gladstone Institute of Virology and Immunology, 1650 Owens St, San Francisco, CA 94158, USA
J Virol 80:1992-9. 2006..In conclusion, our results demonstrate that the defect in HIV replication observed in mature MDDCs stems at least in part from a decline in viral fusion...
In vitro derived dendritic cells trans-infect CD4 T cells primarily with surface-bound HIV-1 virionsMarielle Cavrois
Gladstone Institute of Virology and Immunology, University of California San Francisco, San Francisco, California, United States of America
PLoS Pathog 3:e4. 2007..Our findings suggest that attachment inhibitors could neutralize trans-infection of T cells by DCs in vivo...
HIV-1 virion fusion assay: uncoating not required and no effect of Nef on fusionMarielle Cavrois
Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA 94141-9100, United States
Virology 328:36-44. 2004....
Nef is physically recruited into the immunological synapse and potentiates T cell activation early after TCR engagementDavid Fenard
Gladstone Institute of Virology and Immunology, University of California, 94158, USA
J Immunol 175:6050-7. 2005..g., activated p21-activated kinase-2) into the immunological synapse may underlie the increased frequency of cells expressing transcriptionally active forms of NF-kappaB and NFAT and the resultant changes in T cell activation...
Host factors regulating post-integration latency of HIVSamuel A F Williams
Gladstone Institute of Virology and Immunology, 1650 Owens Street, San Francisco, CA 94158, USA
Trends Microbiol 13:137-9. 2005..Understanding the molecular basis for viral latency is the key first step...
Studies of ebola virus glycoprotein-mediated entry and fusion by using pseudotyped human immunodeficiency virus type 1 virions: involvement of cytoskeletal proteins and enhancement by tumor necrosis factor alphaAkihito Yonezawa
Gladstone Institute of Virology and Immunology, 1650 Owens St, San Francisco, CA 94158, USA
J Virol 79:918-26. 2005..Finally, these studies indicate that pseudotyping in the HIV-1 virion-based fusion assay may be a valuable approach to the study of entry and fusion properties mediated through the envelopes of other viral pathogens...
HIV-1 Vpr displays natural protein-transducing properties: implications for viral pathogenesisMichael P Sherman
Gladstone Institute of Virology and Immunology, San Fransisco, California 94141, USA
Virology 302:95-105. 2002..Native Vpr may thus be optimized for protein transduction, a feature that might enhance and extend the pathological effects of HIV infection...
Insights into the biology of HIV-1 viral protein RMichael P Sherman
Gladstone Institute of Virology and Immunology and Department of Medicine, University of California, San Francisco, California 94141-9100, USA
DNA Cell Biol 21:679-88. 2002..We review the biologic properties of Vpr, focusing on its mechanism of action, role in HIV replication, and significance for host pathogenesis...
Identification of two APOBEC3F splice variants displaying HIV-1 antiviral activity and contrasting sensitivity to VifKara G Lassen
Gladstone Institute of Virology and Immunology, San Francisco, California 94158, USA
J Biol Chem 285:29326-35. 2010..Thus, alternative splicing of A3F mRNA generates truncated antiviral proteins that differ sharply in their sensitivity to Vif...
A sensitive and specific enzyme-based assay detecting HIV-1 virion fusion in primary T lymphocytesMarielle Cavrois
Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA 94141-9100, USA
Nat Biotechnol 20:1151-4. 2002..BlaM cleaves the beta-lactam ring in CCF2, changing its fluorescence emission spectrum from green (520 nm) to blue (447 nm) and thereby allowing fusion to be detected by fluorescence microscopy, flow cytometry, or UV photometry...
Lethal cutaneous disease in transgenic mice conditionally expressing type I human T cell leukemia virus TaxHakju Kwon
Gladstone Institute of Virology and Immunology, San Francisco, California 94158, USA
J Biol Chem 280:35713-22. 2005..Of note, this skin disease completely resolved when Tax transgene expression was suppressed by administration of doxycycline, emphasizing the key role played by this viral oncoprotein in the observed pathology...
Apobec3 encodes Rfv3, a gene influencing neutralizing antibody control of retrovirus infectionMario L Santiago
Gladstone Institute of Virology and Immunology, San Francisco, CA 94158, USA
Science 321:1343-6. 2008..The link between Apobec3 and neutralizing antibody responses highlights an Apobec3-dependent mechanism of host protection that might extend to HIV and other human retroviral infections...
Fluorescence resonance energy transfer-based HIV-1 virion fusion assayMarielle Cavrois
Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA, USA
Methods Mol Biol 263:333-44. 2004..Finally, the assay can also be adapted to study fusion mediated by the envelope proteins from other viruses through the construction of HIV-1 pseudotypes...
HIV vaccine research: the way forwardAnthony S Fauci
National Institute of Allergy and Infectious Diseases, National Institutes of Health, 31 Center Drive, Bethesda, MD 20892, USA
Science 321:530-2. 2008..This article summarizes progress and challenges in HIV vaccine research, the priorities arising from a recent summit at NIAID, and the actions needed, some already under way, to address those priorities...
The CD16+ monocyte subset is more permissive to infection and preferentially harbors HIV-1 in vivoPhilip J Ellery
AIDS Pathogenesis and Clinical Research Program, Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria, Australia
J Immunol 178:6581-9. 2007..Collectively, these data show that CD16+ monocytes are preferentially susceptible to HIV-1 entry, more permissive for replication, and constitute a continuing source of viral persistence during HAART...
A plea for justice for jailed medical workersSunil K Ahuja
Science 314:924-5. 2006
How resting T cells deMURR HIV infectionWarner C Greene
Nat Immunol 5:18-9. 2004
Redistricting the retroviral restriction factorsWarner C Greene
Nat Med 10:778-80. 2004
Human immunodeficiency virus type 1 Vpr induces DNA replication stress in vitro and in vivoErik S Zimmerman
Division of Cellular Biology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA
J Virol 80:10407-18. 2006..We report that infected cells in vivo display an aberrant cell cycle profile whereby a majority of cells have a 4N DNA content, consistent with the onset of G2 arrest...
Rodent cells support key functions of the human immunodeficiency virus type 1 pathogenicity factor NefOliver T Keppler
Department of Virology, University of Heidelberg, Im Neuenheimer Feld 324, D 69120 Heidelberg, Germany
J Virol 79:1655-65. 2005....
Interleukin-18-induced human coronary artery smooth muscle cell migration is dependent on NF-kappaB- and AP-1-mediated matrix metalloproteinase-9 expression and is inhibited by atorvastatinBysani Chandrasekar
Department of Veterans Affairs South Texas Veterans Health Care System, San Antonio, Texas 78229 4404, USA
J Biol Chem 281:15099-109. 2006..Atorvastatin inhibits IL-18-mediated aortic SMC migration and has therapeutic potential for attenuating the progression of atherosclerosis and restenosis...
Cyclophilin A interacts with HIV-1 Vpr and is required for its functional expressionKerstin Zander
Heinrich Pette Institute of Experimental Virology and Immunology, University of Hamburg, D 20251 Hamburg, Germany
J Biol Chem 278:43202-13. 2003....
Research Grants
- ANALYSIS OF THE ROLE OF VPR IN HIV PATHOGENESISWarner Greene; Fiscal Year: 2004..abstract_text> ..
- Microglia and the Neuropathogenesis of HIV DiseaseWarner Greene; Fiscal Year: 2006..This work should both define the utility of this new experimental system for studying neuropathogenesis and provide new information about the pathologic events that may contribute to impairment of neurologic function in HIV disease. ..
- Exploring How HTLV-1 Tax Induces T Cell LeukemiaWarner Greene; Fiscal Year: 2006..Through these combined in vivo and in vitro experiments, we hope to gain key insights into the molecular events underlying HTLV-I Tax mediated leukemogenesis. ..
- Signal Transduction by Cytokine Receptors in VivoWarner Greene; Fiscal Year: 2004..The findings should also point to new, rational therapeutic avenues for reversing these conditions in some settings. ..
- HIV FITNESS, VIRULENCE AND EVOLUTIONWarner Greene; Fiscal Year: 2003....
- Regulation and Action of APOBEC3GWarner Greene; Fiscal Year: 2009..With such understanding, new therapeutic strategies for inhibiting HIV growth could emerge. ..
