Vicente Planelles
Vicente Planelles
affiliation: University of Utah School of Medicine
research area(s): Immunity And Infection, Molecular Biology
Course: Basic and Applied Immunology
University/Istitution: Università Vita-Salute San Raffaele

Baccalaureate Degree 1984 B.S. (Biological Sciences) Universidad Complutense, Madrid, Spain

Masters Degree 1985 M.S. (Plant Physiology) Universidad Complutense, Madrid, Spain

Advanced Degree 1991 Ph.D. (Immunology and Virology) University of California, Davis, CA


1985-1987 Bilingual teacher, Martin Luther King Jr. High School, New York, NY. Selected by the New York Board of Education to teach bilingual classes General Science and Biology
1987-1991 University of California, Davis. Ph.D. Degree in Immunology and Virology. Dr. Paul Luciw, Graduate Advisor.
1991-1995 Division of Hematology-Oncology, UCLA School of Medicine. Laboratory of Dr. Irvin Chen. Postdoctoral Fellow
1996-2002 University of Rochester Cancer Center. Assistant Professor of Hematology-Oncology in Medicine and Microbiology & Immunology
2002-present University of Utah School of Medicine. Associate Professor of Pathology, Division of Cell Biology & Immunology
2004 University of Utah School of Medicine. Department of Patholgy. Award of Tenure.
2008-present University of Utah School of Medicine. Department of Pathology. Professor.
My laboratory has a general interest in the pathogenesis by HIV-1 and other primate lentiviruses. Viral pathogenesis results from the interaction of the viral genes/proteins with those of the host cell. Therefore, a profound knowledge of cellular biology is absolutely required if one wants to understand viral pathogenesis. Because of that, we have acquired and developed tools and knowledge in various areas of cell biology including cell cycle, apoptosis, DNA damage, the ubiquitin/proteasome system, T-cell signaling pathways, and others. Today, our research focuses on two specific areas of HIV pathogenesis:

1. The role of Vpr in viral pathogenesis. Vpr is a multifunctional protein of only 96 amino acid residues. In the context of HIV, Vpr induces cell cycle arrest in G2, followed by apoptosis. Recent investigations from several laboratories have identified a ubiquitin ligase enzyme with the composition Cul4a/DDB1/DCAF1 as the mediator of both of the above cytopathic effects, and perhaps other as yet unknown effects. Vpr directly docks onto the E3 ligase via its substrate specificity module, DCAF1, and presumably redirects the specificity toward a non-cognate substrate. Read more in (DeHart and Planelles, J. Virol 2007, 82:1066).

2. Induction of HIV-1 latency in memory CD4+ T cells, and reactivation of latent viruses. The advent of highly active antiretroviral therapy (HAART) has revealed that, even in the patients who best respond to therapy, virus eradication fails to occur. We now know that there are multiple viral reservoirs that are refractory to inhibition by antiretrovirals. A reservoir that is particularly long lived is the CD4+ memory T-cell subset. HIV-1 latency in this subset appears to be defined by a lack of viral gene expression. In our lab, we have developed a novel assay that recapitulates the transition of CD4+ cells from the activated to the memory stages, and allows for very efficient establishment of latency by HIV-1. Using this system, we are in the process of dissecting the signaling pathways and transcription factors that facilitate or impede both latency and reactivation. Read more in (Bosque and Planelles, Blood 2009, 113:58).
Zimmerman ES, Chen J, Andersen JL, Ardon O, DeHart JL, Blackett J, Choudhary S, Camerini D, Nhiem P, Planelles V: HIV-1 Vpr-mediated G2 arrest requires Rad17 and Hus1 and induces nuclear BRCA1 and γ-H2AX foci formation. Mol Cell Biol 21:9286-9294, 2004.

Andersen JL, Zimmerman ES, DeHart JL, Murala S, Ardon O, Blackett J, Chen J, Planelles V: ATR and GADD45alpha mediate HIV-1 Vpr-induced apoptosis. Cell Death Differentiation 12:326-324, 2005.
DeHart JL, Andersen JL, Zimmerman ES, Ardon O, An D, Blackett J, Planelles V: ATR is dispensable for retroviral integration. J Virol 79:1389-96 2005.

Zimmerman ES, Sherman MP, Blackett JL, Neidleman JA, Kreis C, Mundt P, Williams SA, Warmerdam M, Kahn J, Hecht FM, Grant RM, de Noronha CM, Weyrich AS, Greene WC, Planelles V: HIV-1 Vpr induces DNA replication stress in vitro and in vivo. J Virol 80:10407-10418, 2006.

Andersen JL, DeHart JL, Zimmerman ES, Ardon A, Kim B, Jacquot G, Benichou S and Planelles V: HIV-1 Vpr-induced apoptosis is cell-cycle dependent and requires Bax but not ANT. PLOS pathogens 2:e127, 2006.

DeHart JL, Zimmerman ES, Ardon O, Monteiro-Filho CMR, Argañaraz ER, Planelles V: HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system. Virology J 4:57, 2007.

Dehart JL, Bosque A, Harris RS, Planelles V: HIV-1 Vif induces cell cycle delay via recruitment of the same E3 ubiquitin ligase complex that targets APOBEC3 proteins for degradation. J Virol 82:9265-9272, 2008.

Bosque A, Planelles V: Induction of HIV-1 latency and reactivation in primary memory CD4+ T cells. Blood 113:58-65, 2009.

Kauder SE, Bosque A, Lindqvist A, Planelles V, Verdin E: Epigenetic regulation of HIV-1 latency by cytosine methylation. PLOS Pathogens 5:e1000495, 2009.

Ward J, Davis Z, DeHart JL, Erik Zimmerman ES, Bosque A, Brunetta E, Mavilio D, Planelles V, Barker E: HIV-1 Vpr triggers natural killer cell mediated lysis of infected cells through activation of the ATR-mediated DNA damage response. PLOS Pathogens. 2009: e1000613.

Bosque, A., and V. Planelles. 2010. Studies of HIV-1 latency in an ex vivo model that uses primary central memory T cells. Methods 2011, 53:54-61

Shah, A. H., B. Sowrirajan, Z. B. Davis, J. P. Ward, E. M. Campbell, V. Planelles, and E. Barker. 2010. Degranulation of natural killer cells following interaction with HIV-1-infected cells is hindered by downmodulation of NTB-A by Vpu. Cell Host Microbe 8:397-409.
Project Title:
Signaling pathways involved in reactivation of latent HIV in central memory cells
The HIV-1 promoter contains a number of characterized transcription factor binding sites. Cellular factors bind to these sites under certain conditions and trigger recruitment and activation of the cellular transcription machinery. This reactivates latent viruses. We are interested in understanding the various cellular stimuli that can activate transcription, so that we can have a complete picture of how the latent reservoir is regulated in vivo or under the influence of therapeutic interventions.