Hillel Haim, MD, PhD

Portrait
Assistant Professor of Microbiology and Immunology

Contact Information

Office: 3-770 Bowen Science Building
51 Newton Rd
Iowa City, IA 52242
319-335-9989

Lab: 3-701 Bowen Science Building
51 Newton Rd
Iowa City, IA 52242
319-335-7819

Education

BS, Medical Sciences, Hebrew University of Jerusalem
MD, Medicine, Hebrew University of Jerusalem
PhD, Virology, Hebrew University of Jerusalem

Postdoctoral Fellow, Virology, Harvard Medical School

Education/Training Program Affiliations

Biomedical Science Program, Department of Microbiology Graduate Program

Research Summary

The envelope glycoprotein (Env) spike on the surface of human immunodeficiency virus type 1 (HIV-1) serve as the viral fusion machinery and allows entry of the virus into host cells. As the only virus-encoded component on the surface of the HIV-1 particle, Env is also a primary target for the immune response of the host and has thus been the focus of antibody-based vaccine design. My research centers on characterizing the molecular basis of HIV-1 fusion and inhibition by antibodies and on the forces that guide the evolution of these tightly-linked properties in the infected host.

The Env subunits are compacted into a high potential energy complex on the surface of the HIV-1 particle. This energy is used to drive the fusion process and therefore needs to be maintained until the virus reaches the target cell surface, where it can be released through specific interactions with host cell receptors. Premature loss of this energy (e.g., through interaction with an antibody) will result in loss of function and thus inactivation of the virus. Through recent work we have shown how the energetics of Env directly affect the sensitivity of the virus to inactivation by antibodies. The basic parameters that determine the sensitivity of HIV-1 to inactivation by host antibodies could thus be defined. We found that inactivation is strongly affected by the propensity of Env to transition to lower energy states and by the propensity of the antibody to induce such transitions. Incorporation of these measurable parameters into a model allowed us for the first time to predict the sensitivity of a given HIV-1 strain to a given antibody. Importantly, these findings define a new framework for understanding how a virus is inhibited by host antibodies, based on changes in energy state.

The research in my lab is aimed at defining the architecture of the energy landscape of HIV-1 Env and its relationship with both function and sensitivity of the virus to host antibodies. What are the different energy states that Env can sample? How are transitions achieved between different states? Importantly, how can we regulate such transitions? This work will be complemented by comprehensive studies of the evolution of Env structure and energy landscape in individual patients and at higher-order levels. In our work we combine the disciplines of virology, immunology and genetics. The tools we use to address our questions are also varied, from the fields of molecular biology, biochemistry, biophysics and mathematics. Through strong collaborations with several clinical groups across the US, the models that we generate are tested thoroughly.

Publications

Johnson, J., Zhai, Y., Salimi, H., Espy, N., Eichelberger, N., DeLeon, O., O'Malley, Y., Courter, J., Smith 3rd, A. B., Madani, N., Sodroski, J. & Haim, H. (2017). Induction of a Tier-1-like Phenotype in Diverse Tier-2 Isolates by Agents that Guide HIV-1 Env to Perturbation-sensitive, Non-native States. J Virol, 91(15), e00174-17. PMID: 28490588.

McLinden, J. H., Bhattarai, N., Stapleton, J. T., Chang, Q., Kaufman, T. M., Cassel, S. L., Sutterwala, F. S., Haim, H., Houtman, J. C. & Xiang, J. (2017). Yellow Fever Virus, but Not Zika Virus or Dengue Virus, Inhibits T-Cell Receptor-Mediated T-Cell Function by an RNA-Based Mechanism. J Infect Dis, 216(9), 1164-1175. PMID: 28968905.

DeLeon, O., Hodis, H., O'Malley, Y., Johnson, J., Salimi, H., Zhai, Y., Winter, E., Remec, C., Eichelberger, N., Van Cleave, B., Puliadi, R., Harrington, R. D., Stapleton, J. T. & Haim, H. (2017). Accurate predictions of population-level changes in sequence and structural properties of HIV-1 Env using a volatility-controlled diffusion model. PLoS Biol, 15(4), e2001549. PMID: 28384158.

Fernández-Oliva, A., Finzi, A., Haim, H., Menéndez-Arias, L., Sodroski, J. & Pacheco, B. (2015). HIV-1 Adapts To Replicate in Cells Expressing Common Marmoset APOBEC3G and BST2. J Virol, 90(2), 725-40. PMID: 26512082.

McGee, K., Haim, H., Korioth-Schmitz, B., Espy, N., Javanbakht, H., Letvin, N. & Sodroski, J. (2014). The selection of low envelope glycoprotein reactivity to soluble CD4 and cold during simian-human immunodeficiency virus infection of rhesus macaques. J Virol, 88(1), 21-40. PMID: 24131720.

Yen, P. J., Herschhorn, A., Haim, H., Salas, I., Gu, C., Sodroski, J. & Gabuzda, D. (2014). Loss of a conserved N-linked glycosylation site in the simian immunodeficiency virus envelope glycoprotein V2 region enhances macrophage tropism by increasing CD4-independent cell-to-cell transmission. J Virol, 88(9), 5014-28. PMID: 24554659.

Haim, H., Salas, I. & Sodroski, J. (2013). Proteolytic processing of the human immunodeficiency virus envelope glycoprotein precursor decreases conformational flexibility. J Virol, 87(3), 1884-9. PMID: 23175369.

Haim, H., Salas, I., McGee, K., Eichelberger, N., Winter, N., Pacheco, B. & Sodroski, J. (2013). Modeling virus- and antibody-specific factors to predict human immunodeficiency virus neutralization efficiency. Cell Host Microbe, 14(5), 547-58. PMID: 24237700.

Mao, Y., Wang, L., Gu, C., Herschhorn, A., Xiang, S. H., Haim, H., Yang, X. & Sodroski, J. (2012). Subunit organization of the membrane-bound HIV-1 envelope glycoprotein trimer. Nat Struct Mol Biol, 19(9), 893-9. PMID: 22864288.

Haim, H., Strack, B., Kassa, A., Madani, N., Wang, L., Courter, J. R., Princiotto, A., McGee, K., Pacheco, B., Seaman, M. S., Smith, A. B. & Sodroski, J. (2011). Contribution of intrinsic reactivity of the HIV-1 envelope glycoproteins to CD4-independent infection and global inhibitor sensitivity. PLoS Pathog, 7(6), e1002101. PMID: 21731494.

Koh, Y., Haim, H. & Engelman, A. (2011). Identification and characterization of persistent intracellular human immunodeficiency virus type 1 integrase strand transfer inhibitor activity. Antimicrob Agents Chemother, 55(1), 42-9. PMID: 21060108.

Wilen, C. B., Parrish, N. F., Pfaff, J. M., Decker, J. M., Henning, E. A., Haim, H., Petersen, J. E., Wojcechowskyj, J. A., Sodroski, J., Haynes, B. F., Montefiori, D. C., Tilton, J. C., Shaw, G. M., Hahn, B. H. & Doms, R. W. (2011). Phenotypic and immunologic comparison of clade B transmitted/founder and chronic HIV-1 envelope glycoproteins. J Virol, 85(17), 8514-27. PMID: 21715507.

Zhukovsky, M. A., Basmaciogullari, S., Pacheco, B., Wang, L., Madani, N., Haim, H. & Sodroski, J. (2010). Thermal stability of the human immunodeficiency virus type 1 (HIV-1) receptors, CD4 and CXCR4, reconstituted in proteoliposomes. PLoS One, 5(10), e13249. PMID: 20967243.

Haim, H., Si, Z., Madani, N., Wang, L., Courter, J. R., Princiotto, A., Kassa, A., DeGrace, M., McGee-Estrada, K., Mefford, M., Gabuzda, D., Smith, A. B. & Sodroski, J. (2009). Soluble CD4 and CD4-mimetic compounds inhibit HIV-1 infection by induction of a short-lived activated state. PLoS Pathog, 5(4), e1000360. PMID: 19343205.

Kassa, A., Madani, N., Schön, A., Haim, H., Finzi, A., Xiang, S. H., Wang, L., Princiotto, A., Pancera, M., Courter, J., Smith, A. B., Freire, E., Kwong, P. D. & Sodroski, J. (2009). Transitions to and from the CD4-bound conformation are modulated by a single-residue change in the human immunodeficiency virus type 1 gp120 inner domain. J Virol, 83(17), 8364-78. PMID: 19535453.

Kolodkin-Gal, D., Zamir, G., Edden, Y., Pikarsky, E., Pikarsky, A., Haim, H., Haviv, Y. S. & Panet, A. (2008). Herpes simplex virus type 1 preferentially targets human colon carcinoma: role of extracellular matrix. J Virol, 82(2), 999-1010. PMID: 17977977.

Haim, H., Steiner, I. & Panet, A. (2007). Time frames for neutralization during the human immunodeficiency virus type 1 entry phase, as monitored in synchronously infected cell cultures. J Virol, 81(7), 3525-34. PMID: 17251303.

Haim, H., Steiner, I. (2006). Gene Therapy to the Nervous System. In A. Battler , J. Leor (Eds.) Stem cell and Gene-based Therapy: Frontiers in Regenerative Medicine. pp. 133-154. Springer, London.

Haim, H., Steiner, I. & Panet, A. (2005). Synchronized infection of cell cultures by magnetically controlled virus. J Virol, 79(1), 622-5. PMID: 15596857.

Mador, N., Braun, E., Haim, H., Ariel, I., Panet, A. & Steiner, I. (2003). Transgenic mouse with the herpes simplex virus type 1 latency-associated gene: expression and function of the transgene. J Virol, 77(23), 12421-9. PMID: 14610166.