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TRIM5 and Innate Resistance to HIV-1

English title TRIM5 and Innate Resistance to HIV-1
Applicant Luban Jeremy
Number 113558
Funding scheme Project funding (Div. I-III)
Research institution Dépt Microbiologie et Médecine Moléculaire Faculté de Médecine Université de Genève
Institution of higher education Università della Svizzera italiana - USI
Main discipline Experimental Microbiology
Start/End 01.10.2006 - 30.09.2009
Approved amount 736'320.00
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Keywords (5)

HIV-1; retrovirus; TRIM5; restriction; SPRY

Lay Summary (English)

Lead
Lay summary
Independent experiments from our lab and the lab of Joseph Sodroski recently identified TRIM5 as a factor in the cells of humans and other primates that confers resistance to infection by HIV-1 and other retroviruses. TRIM5 can be thought of as a cytoplasmic receptor that recognizes the complex retroviral core structure encasing the viral genomic RNA, in a CA-specific manner. Along with another anti-retrovirus factor called Fv1, it establishes a paradigm of innate immunity in which an invading multiprotein complex, rather than double-stranded RNA or lipopolysaccharide, is recognized by a specific receptor. Here, using a combination of complementary approaches, the mechanism by which TRIM5 inhibits retroviral infection will be deciphered. In the first specific aim the genetic requirements for recognition of the retrovirus capsid by human TRIM5α will be determined. These studies will exploit novel biochemical assays for specific recognition of mature virion cores by human TRIM5α. In the second specific aim screens for host factors essential to retroviral restriction by TRIM5α will be conducted using cell clones in which TRIM5α is not sufficient for restriction.Finally, in a directed set of experiments the importance for retroviral restriction of ubiquitin and TRIM5-associated E3 ubiquitin ligase activity will be tested. These experiments will extend knowledge concerning the mechanisms of innate immunity to HIV-1. By doing so it is expected that these studies will contribute to the development of novel approaches for preventing HIV-1 infection and for blocking progression to AIDS in those individuals already infected with this lethal virus.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Associated projects

Number Title Start Funding scheme
128666 Gamma Irradiator for Research in Immunology, Infectious Diseases, Stem Cell Biology, and Neurobiology 01.12.2009 R'EQUIP
128655 TRIM5 and Innate Resistance to HIV-1 01.10.2009 Project funding (Div. I-III)

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