Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The evolution of drug resistant strains poses a significant challenge for effective long-term treatment of human immunodeficiency virus type 1 (HIV-1) infection. One counter-measure against resistant strains is treatment with novel therapeutics. Several areas of HIV replication are potential targets for the development of new therapies. The goal of our research is to elucidate the assembly and transport of the HIV preintegration complex (PIC) to aid in the development of novel antiretroviral therapeutics. PICs are large viral DNA complexes formed during early HIV-1 infection of cells that target the viral DNA into the nuclei of cells after reverse transcription. Due to challenges in producing and purifying sufficient quantities of PICs there is limited understanding of their composition, assembly, and mechanism of the transport. Consequently, there are no inhibitors of PICs in development. The objective of our studies is to identify and characterize novel cellular components of HIV-1 PICs. We have undertaken two ambitious strategies to identify PIC-associated cellular proteins. First is a targeted proteomic analysis of PICs partially purified by velocity gradient centrifugation. Second, is a proteomic analysis of PICs affinity purified by specific biotinylation of HIV-1 proteins. Using both methods we have identified several candidate HIV dependency factors (HDFs). Candidate HDFs will be assessed for their interaction with HIV components and their role in HIV replication. Successful completion of these studies will advance the understanding of early events of HIV replication and discover new targets for the development of antiviral therapies.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR015635-10
Application #
7959393
Study Section
Special Emphasis Panel (ZRR1-RI-8 (01))
Project Start
2009-05-01
Project End
2010-04-30
Budget Start
2009-05-01
Budget End
2010-04-30
Support Year
10
Fiscal Year
2009
Total Cost
$178,440
Indirect Cost

  Institution

Name
University of Nebraska Lincoln
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
555456995
City
Lincoln
State
NE
Country
United States
Zip Code
68588

  Publications

De Castro, Cristina; Klose, Thomas; Speciale, Immacolata et al. (2018) Structure of the chlorovirus PBCV-1 major capsid glycoprotein determined by combining crystallographic and carbohydrate molecular modeling approaches. Proc Natl Acad Sci U S A 115:E44-E52
Yuan, Qi; Telling, Glenn; Bartelt-Hunt, Shannon L et al. (2018) Dehydration of Prions on Environmentally Relevant Surfaces Protects Them from Inactivation by Freezing and Thawing. J Virol 92:
Liu, Yilin; Jones, Clinton (2016) Regulation of Notch-mediated transcription by a bovine herpesvirus 1 encoded protein (ORF2) that is expressed in latently infected sensory neurons. J Neurovirol 22:518-28
Langenfeld, Katie A; Shikiya, Ronald A; Kincaid, Anthony E et al. (2016) Incongruity between Prion Conversion and Incubation Period following Coinfection. J Virol 90:5715-23
Liu, Yilin; Hancock, Morgan; Workman, Aspen et al. (2016) ?-Catenin, a Transcription Factor Activated by Canonical Wnt Signaling, Is Expressed in Sensory Neurons of Calves Latently Infected with Bovine Herpesvirus 1. J Virol 90:3148-59
De Castro, Cristina; Speciale, Immacolata; Duncan, Garry et al. (2016) N-Linked Glycans of Chloroviruses Sharing a Core Architecture without Precedent. Angew Chem Int Ed Engl 55:654-8
Destache, Christopher J; Mandal, Subhra; Yuan, Zhe et al. (2016) Topical Tenofovir Disoproxil Fumarate Nanoparticles Prevent HIV-1 Vaginal Transmission in a Humanized Mouse Model. Antimicrob Agents Chemother 60:3633-9
Lingel, Amy; Ehlers, Erica; Wang, Qianli et al. (2016) Kaposi's Sarcoma-Associated Herpesvirus Reduces Cellular Myeloid Differentiation Primary-Response Gene 88 (MyD88) Expression via Modulation of Its RNA. J Virol 90:180-8
Liu, Fang; Huang, Yunlong; Zhang, Fang et al. (2015) Macrophages treated with particulate matter PM2.5 induce selective neurotoxicity through glutaminase-mediated glutamate generation. J Neurochem 134:315-26
Lai, Siqiang; Zhang, Min; Xu, Dongsheng et al. (2015) Direct reprogramming of induced neural progenitors: a new promising strategy for AD treatment. Transl Neurodegener 4:7

Showing the most recent 10 out of 429 publications