Abstract

The primary aim of this project is to better understand the role of the HIV envelope protein to HIV pathogenesis. To that end, we have focused on the complex interplay between the viral envelope and several of the known cell surface receptors to which it binds. We are particularly interested in the role of envelope-mediated signal transduction in HIV pathogenesis. gp120 engages integrin α4β7, the gut-homing receptor, opens up many new and potentially important questions. Because α4β7 mediates leukocyte homing to gut associated lymphoid tissue, which is a principal site of HIV replication during the acute phase of infection we have set out to explore the role of α4β7 expressing CD4+ T cells in HIV transmission. We tested this hypothesis in a non-human primate model of HIV/SIV infection, and determined that an antibody specific for α4β7 prevented transmission in a rhesus macaque model of mucosal transmission. In addition, we have investigated the interaction between HIV and α4β7 on primary B cells. We have learned that some of the defects associated with HIV disease result from direct interactions between gp120 and receptors on B cells.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAI000887-15
Application #
9161531
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
15
Fiscal Year
2015
Total Cost
Indirect Cost

  Institution

Name
Niaid Extramural Activities
Department
Type
DUNS #
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  Publications

Yolitz, Jason; Schwing, Catherine; Chang, Julia et al. (2018) Signal peptide of HIV envelope protein impacts glycosylation and antigenicity of gp120. Proc Natl Acad Sci U S A 115:2443-2448
Arthos, James; Cicala, Claudia; Nawaz, Fatima et al. (2018) The Role of Integrin ?4?7 in HIV Pathogenesis and Treatment. Curr HIV/AIDS Rep 15:127-135
Sivro, Aida; Schuetz, Alexandra; Sheward, Daniel et al. (2018) Integrin ?4?7 expression on peripheral blood CD4+ T cells predicts HIV acquisition and disease progression outcomes. Sci Transl Med 10:
Santangelo, P J; Cicala, C; Byrareddy, S N et al. (2018) Early treatment of SIV+ macaques with an ?4?7 mAb alters virus distribution and preserves CD4+ T cells in later stages of infection. Mucosal Immunol 11:932-946
Calenda, Giulia; Keawvichit, Rassamon; Arrode-Brusés, Géraldine et al. (2018) Integrin ?4?7 Blockade Preferentially Impacts CCR6+ Lymphocyte Subsets in Blood and Mucosal Tissues of Naive Rhesus Macaques. J Immunol 200:810-820
Nawaz, Fatima; Goes, Livia R; Ray, Jocelyn C et al. (2018) MAdCAM costimulation through Integrin-?4?7 promotes HIV replication. Mucosal Immunol 11:1342-1351
Kijak, Gustavo H; Sanders-Buell, Eric; Chenine, Agnes-Laurence et al. (2017) Rare HIV-1 transmitted/founder lineages identified by deep viral sequencing contribute to rapid shifts in dominant quasispecies during acute and early infection. PLoS Pathog 13:e1006510
Kijak, Gustavo H; Sanders-Buell, Eric; Chenine, Agnes-Laurence et al. (2017) Correction: Rare HIV-1 transmitted/founder lineages identified by deep viral sequencing contribute to rapid shifts in dominant quasispecies during acute and early infection. PLoS Pathog 13:e1006620
Girard, Alexandre; Jelicic, Katija; Van Ryk, Don et al. (2017) Neutralizing and Targeting Properties of a New Set of ?4?7-Specific Antibodies Are Influenced by Their Isotype. J Acquir Immune Defic Syndr 75:118-127
Cicala, Claudia; Nawaz, Fatima; Jelicic, Katija et al. (2016) HIV-1 gp120: A Target for Therapeutics and Vaccine Design. Curr Drug Targets 17:122-35

Showing the most recent 10 out of 25 publications