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Spear
Greg
PhD
Professor
Immunology-Microbiology
Graduate College, Rush Medical College
1735 W. Harrison Street, Cohn Building, Room 626, Chicago, IL 60612
1735 W. Harrison Street, Cohn Building, Room 636, Chicago, IL 60612
(312) 942-2083
(312) 942-2808
gspear@rush.edu
PhD, University of Illinois, 1984
Bacteria, Bacterial Infections and Mycoses, Biological Phenomena Cell Phenomena and Immunity, Female Genital Diseases and Pregnancy Complications, Immune System Diseases, Virus Diseases, Viruses
Our research group works on three areas that are all based in the immunology of virus infections, with a focus on innate immunity and HIV.

A. The effect of lower genital tract bacterial flora on HIV infection.

B. The interaction of the complement system with viruses.

C. Initial steps (binding) in the infection of cells by HIV.

A. The effect of lower genital tract bacterial flora on HIV infection. Epidemiologic studies show that changes in the genital tract flora increase the susceptibility of women to infection by HIV. Healthy genital tract flora consists mostly of different types of lactobacilli. Bacterial vaginosis (BV) is a common condition where the lactobacilli are replaced by a number of other bacteria. We are studying the mechanism by which BV bacteria can increase HIV susceptibility. We also study how other genital tract infections such as candida and HSV-2 alter HIV infection.

B. Interaction of viruses with the complement system. The complement system in blood can be activated by micro-organisms through three pathways; alternative, classical and lectin. The lectin pathway is initiated by binding mannose binding lectin (MBL) to pathogens. We study the interaction of MBL with HIV. HIV interacts with MBL through high mannose carbohydrates on the HIV envelope. Recent studies show that Ebola and Marburg viruses also bind MBL and activate complement.

C. Initial steps (binding) in the infection of cells by HIV. Binding of viruses to cells is a critical first step in infection. We recently found that HIV binds to primary mononuclear cells via a calcium-dependent interaction. This interaction is also dependent on a cell-surface protein and on cell-surface N-linked glycans. This data suggests a model where HIV takes with it a C-type lectin as it buds from infected CD+ lymphocytes. The C-type lectin then binds to N-linked glycans on target cells thereby factilitating infection.

Members of the Spear Lab group
Current lab members
M. Reza Zariffard, PhD, research associate
Xin Ji, PhD, research associate
Elizabeth St. John, BS, graduate student
Jill Bianchi, BS, research technician

Recent lab members
Josh Anzinger, PhD
Sal Harwani, MD
Debra Mares, BS

Selected Publications:
Olinger GG, M Saifuddin, ML Hart and GT Spear. 2002. Cellular factors influence the binding of HIV-1 to cells. AIDS Research and Human Retroviruses 18:259-267.

Takefman DM, Spear GT, Saifuddin M and Wilson CA. 2002. Human CD59 Incorporation into Porcine Endogenous Retrovirus Particles: Implications for the Use of Transgenic Pigs for Xenotransplantation. J Virol 76:1999-2002.

Hart M, Saifuddin M, Kawasaki, Hooker and Spear GT. 2002. High Mannose Glycans and Sialic Acid on gp120 Regulate Binding of Mannose-Binding Lectin (MBL) to HIV-1. AIDS Res Hu Retrovir 18:(17)1311-1317.

ML Hart, M Saifuddin and GT Spear. 2003. Glycosylation inhibitors and neuraminidase enhance HIV-1 binding and neutralization by mannose-binding lectin (MBL) J Gen Virol 84:353-360.

MR Zariffard, M Saifuddin, BE Sha and GT Spear. 2002. Detection of Bacterial Vaginosis-related organisms by Real-Time PCR for Lactobacilli, Gardnerella vaginalis and Mycoplasma hominis. FEMS Immunology and Medical Microbiology 34(4):277-8

Spear GT, Zariffard MR, Xin J, Saifuddin M. 2003. Inhibition of DC-SIGN-mediated trans infection of T cells by mannose-binding lectin. Immunology. Sep;110(1):80-5.

Ying H, X Ji, ML Hart, K Gupta, M Saifuddin, MR Zariffard and GT Spear. 2004. Interaction of Mannose Binding Lectin with HIV-1 is sufficient for virus opsonization but not neutralization. AIDS Res Hu Retrovir 20:327

Zariffard MR, S Harwani, RM Novak, PJ Graham, J Xin, and GT Spear. 2004. Trichomonas vaginalis Infection Activates Cells Through Toll-Like Receptor 4. Clin. Immunol. 111:103-107.

Gabali AM, J Anzinger, GT Spear, and LL Thomas. 2004. Activation of Inflammatory Stimuli Increases Neutrophil Binding of HIV-1 and Subsequent Infection of Lymphocytes by the Bound Virus. Journal of Virology 78:10833

H Zhang, Y Huang, R Fayad, GT Spear, L Qiao. 2004. Induction of Mucosal and Systemic Neutralizing Antibodies to HIV by Oral Immunization with Papillomavirus-HIVgp41 Chimeric Viruslike Particles. J Virol 78:8342-8

BE Sha, MR Zariffard, QJ Wang, HY Chen, J Bremer, MH Cohen, GT Spear. 2005. Female Genital Tract HIV Load Correlates Inversely with Lactobacillus spp. But Positively with Bacterial Vaginosis and Mycoplasma hominis. J Infect Dis 191:25-32.

Ji X, H Gewurz and GT Spear. 2005. Mannose Binding Lectin (MBL) and HIV. Molecular Immunology. 42(2):145-52

M. Reza Zariffard, Richard Novak, Nell Lurain, Beverly E. Sha, Parrie Graham and Gregory T. Spear. 2005. Induction of TNF-a Secretion and Toll-Like Receptor 4 Expression by Genital tract Secretions from Women with Bacterial Vaginosis. J Inf Dis 191:1913-21

Xin Ji, Gene G. Olinger, Sheena Aris, and Gregory T. Spear. 2005. Mannose Binding Lectin Binds to Ebola and Marburg Envelope Glycoproteins Resulting in Blocking of Virus Interaction with DC-SIGN and Complement-Mediated Virus Neutralization. J Gen Virol 86:2535-42

JA Cohn, FB Hashemi, M Camarca, F Kong, J Xu, SK Beckner, AA Kovacs, PS Reichelderfer, GT Spear. 2005. HIV Inducing Factor in Cervicovaginal Secretions is Associated with Bacterial Vaginosis in HIV-1 Infected Women. J Acq Imm Def Syn 39(3):340-346

Beverly E. Sha, M. Reza Zariffard, Qiong J. Wang, Hua Y. Chen, Mardge H. Cohen, GT Spear. 2005. Utility of Amsel Criteria, Nugent Score, and Quantitative Bacterial PCR for Predicting Bacterial Vaginosis in HIV-infected Women. J Clin Micro 43:4607.

Gregory T. Spear, M.E.A.F. Alves, Mardge Cohen, James Bremer and Alan L. Landay. 2005. Relationship of HIV RNA and Cytokines in Saliva and Plasma from HIV-infected Persons FEMS Immunol Med Microbiol 45:129

M. Reza. Zariffard, Beverly E. Sha, Qiong J. Wang, Hua Y. Chen, James Bremer, Mardge H. Cohen and Gregory T. Spear. 2005. Relationship of U1-cell HIV-Stimulatory Activity to Bacterial Vaginosis and HIV Genital Tract Virus Load - AIDS Research and Human Retro 21:945

Ji X, Chen Y, Faro J, Gewurz H, Bremer J and Spear GT. 2006. Interaction of Human Immunodeficiency Virus (HIV) Glycans with Lectins of the Human Immune System. Current Protein and Peptide Science 7(4):317-24

Anzinger J, Mezo I, Ji X, Gabali A, Thomas L, Spear GT. 2006. HIV infection of mononuclear cells is calcium-dependent. Virus Research. 122(1-2):183-8

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