HIV; Molecular Biology; Infectious Disease Medicine
Public Health Interests
Stem Cell Center, Yale: Transcriptional Regulation of Stem and Progenitor Cells
Our laboratory is focused on the study of human immunodeficiency virus type I (HIV) replication and the development of small animal models of HIV. For example, mice are not susceptible to HIV due a profound block in HIV assembly and release from cells. We are exploring the nature of this block and are conducting genetic screens and biochemical assays to identify human genes that may be able to overcome this deficiency. Our work has zeroed in on Crm1, and we are now attempting to determine why murine Crm1 is defective in terms of HIV replication.
We also utilize replication-defective HIV as a vector to transduce non-dividing cells for gene therapeutic purposes and are developing novel methods of vector production. These vectors are used to investigate other viruses (for example, cellular binding and entry requirements of Ebola and Western Equine Encephalitis) and to explore fundamental questions in molecular biology, such as high throughput identification of DNA elements that serve as transcriptional activators in various cell types, including human embryonic stem cells.
We are now funded through NIDA to use advanced genomic and genetic techniques to identify host genes associated with control of HIV in man. We are studying HIV+ elite controllers, a select subset of patients who are able to control the virus in the absence of therapy. Using a combination of molecular biology and genomic methods, we hope to pinpoint the genes causally responsible for elite control, at least in the patients who manifest a distinct in vitro phenotype. This work may inform both the HIV vaccine and eradication effort.
In collaboration with Dr. Priti Kumar, also of the ID section, we are funded by the NIH to examine the possibility of using adenoviral-vectored anti-HIV broadly neutralizing antibodies to counteract HIV, both as prophylaxis and as therapy, exploring their use in humanized murine models.
Specialized Terms: HIV replication and the development of small animal models of HIV; HIV vectors; HIV replication and gene transfer into non-dividing cells
- UBXN1 Interferes with Rig-I-like Receptor-Mediated Antiviral Immune Response by Targeting MAVS Wang, P. et al. UBXN1 Interferes with Rig-I-like Receptor-Mediated Antiviral Immune Response by Targeting MAVS. Cell Reports, in press.
- Human CRM1 augments production of infectious human and feline immunodeficiency viruses from murine cells. Elinav, H. et al. Human CRM1 augments production of infectious human and feline immunodeficiency viruses from murine cells. J. Virology 86: 12053-68, 2012.
- High level production of replication-defective human immunodeficiency type 1 virus vector particles using helper-dependent adenovirus vectors. Hu, Y, O’Boyle, K, Palmer, D, Ng, P, & Sutton, RE. High level production of replication-defective human immunodeficiency type 1 virus vector particles using helper-dependent adenovirus vectors. Mol Ther-Methods & Clin Development, in press.
- Increased levels of MIPs result in resistance to R5-tropic HIV-1 in a subset of Elite Controllers. Walker, WE, Kurscheid, S, Joshi, S, Lopez, CA, Goh, G, Choi, M, Barakat, L, Francis, J, Ann Fisher, A, Kozal, M, Zapata, H, Shaw, A, Lifton, R, Sutton, RE#, & Fikrig, EF#. Increased levels of MIPs result in resistance to R5-tropic HIV-1 in a subset of Elite Controllers. Journal of Virology, in press. #Co-senior authors.
- Adenovirus-Vectored Broadly Neutralizing Antibodies Directed Against gp120 Prevent Human Immunodeficiency Virus Type 1 Acquisition in Humanized Mice Liu, S, Jackson, A, Beloor, J, Kumar, P, & Sutton, R. Adenovirus-vectored broadly neutralizing antibodies directed against gp120 prevent HIV-1 acquisition in humanized mice, Hum Gene Ther, in press.
Full List of PubMed Publications
- Hu Y, O'Boyle K, Auer J, Raju S, You F, Wang P, Fikrig E, Sutton RE: Multiple UBXN family members inhibit retrovirus and lentivirus production and canonical NFκΒ signaling by stabilizing IκBα. PLoS Pathog. 2017 Feb 2; 2017 Feb 2. PMID: 28152074
- Zhang X, Justice AC, Hu Y, Wang Z, Zhao H, Wang G, Johnson EO, Emu B, Sutton RE, Krystal JH, Xu K: Epigenome-wide differential DNA methylation between HIV-infected and uninfected individuals. Epigenetics. 2016 Aug 12; 2016 Aug 12. PMID: 27672717
- Liu S, Jackson A, Beloor J, Kumar P, Sutton RE: Adenovirus-Vectored Broadly Neutralizing Antibodies Directed Against gp120 Prevent Human Immunodeficiency Virus Type 1 Acquisition in Humanized Mice. Hum Gene Ther. 2015 Sep; 2015 Aug 11. PMID: 25953321
- Farber SJ, Sutton RE: HIV+ patient on suppressive antiretroviral therapy with steroid injection-induced myopathy. AIDS. 2015 Jul 17. PMID: 26098599
- Walker WE, Kurscheid S, Joshi S, Lopez CA, Goh G, Choi M, Barakat L, Francis J, Fisher A, Kozal M, Zapata H, Shaw A, Lifton R, Sutton RE, Fikrig E: Increased Levels of Macrophage Inflammatory Proteins Result in Resistance to R5-Tropic HIV-1 in a Subset of Elite Controllers. J Virol. 2015 May; 2015 Mar 4. PMID: 25740989
- Hu Y, O'Boyle K, Palmer D, Ng P, Sutton RE: High-level production of replication-defective human immunodeficiency type 1 virus vector particles using helper-dependent adenovirus vectors. Mol Ther Methods Clin Dev. 2015 Mar 18; 2015 Mar 18. PMID: 26029715
- Parker CG, Dahlgren MK, Tao RN, Li DT, Douglass EF Jr, Shoda T, Jawanda N, Spasov KA, Lee S, Zhou N, Domaoal RA, Sutton RE, Anderson KS, Jorgensen WL, Krystal M, Spiegel DA: Illuminating HIV gp120-Ligand Recognition through Computationally-Driven Optimization of Antibody-Recruiting Molecules. Chem Sci. 2014 Jun 1. PMID: 25379167
- You F, Wang P, Yang L, Yang G, Zhao YO, Qian F, Walker W, Sutton R, Montgomery R, Lin R, Iwasaki A, Fikrig E: ELF4 is critical for induction of type I interferon and the host antiviral response. Nat Immunol. 2013 Dec; 2013 Nov 3. PMID: 24185615
- Wang P, Yang L, Cheng G, Yang G, Xu Z, You F, Sun Q, Lin R, Fikrig E, Sutton RE: UBXN1 interferes with Rig-I-like receptor-mediated antiviral immune response by targeting MAVS. Cell Rep. 2013 Apr 25; 2013 Mar 28. PMID: 23545497
- Elinav H, Wu Y, Coskun A, Hryckiewicz K, Kemler I, Hu Y, Rogers H, Hao B, Ben Mamoun C, Poeschla E, Sutton R: Human CRM1 augments production of infectious human and feline immunodeficiency viruses from murine cells. J Virol. 2012 Nov; 2012 Aug 29. PMID: 22933280
- Scheideman EH, Marlatt SA, Xie Y, Hu Y, Sutton RE, DiMaio D: Transmembrane protein aptamers that inhibit CCR5 expression and HIV coreceptor function. J Virol. 2012 Oct; 2012 Jul 18. PMID: 22811524