Abstract

The focus of this project is to gain new knowledge regarding the very early events following mucosal transmission of HIV. We are particularly focused on molecular interactions between the viral envelope and cell surface receptors that are expressed on CD4 + T cells. This information is fundamental to the development of an effective HIV vaccine. We have shown previously that the infection of a4b7-expressing CD4+ T cells is one of these early events. In addition, we showed that the HIV envelope protein gp120 binds directly to integrin a4b7 and that this interaction is mediated by the V2 domain of gp120. Our approach in 2019 was to define the types of monoclonal antibodies that interfere with this interaction. Such information will hopefully aid in the design and development of an effective HIV vaccine.

  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 #
1ZIAAI000883-19
Application #
10014083
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
19
Fiscal Year
2019
Total Cost
Indirect Cost

  Institution

Name
National Institute of Allergy and Infectious Diseases
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Kononchik, Joseph; Ireland, Joanna; Zou, Zhongcheng et al. (2018) HIV-1 targets L-selectin for adhesion and induces its shedding for viral release. Nat Commun 9:2825
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
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
Ma, Xiaochu; Lu, Maolin; Gorman, Jason et al. (2018) HIV-1 Env trimer opens through an asymmetric intermediate in which individual protomers adopt distinct conformations. Elife 7:
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:
Wang, Shixia; Chou, Te-Hui; Hackett, Anthony et al. (2017) Screening of primary gp120 immunogens to formulate the next generation polyvalent DNA prime-protein boost HIV-1 vaccines. Hum Vaccin Immunother 13:2996-3009
Plotnik, David; Guo, Wenjin; Cleveland, Brad et al. (2017) Extracellular Matrix Proteins Mediate HIV-1 gp120 Interactions with ?4?7. J Virol 91:

Showing the most recent 10 out of 43 publications