Abstract

Understanding the earliest events following mucosal transmission of HIV is fundamental to the development of an effective HIV vaccine; yet, these events are not well defined. We have shown previously that the infection of a4b7-expressing CD4+ T cells is one of these early events. Our approach in 2018 was to 1) further define the interaction between the virus and these cells, 2) assess the potential for signal transduction through a4b7 to promote viral replication in PBMCs from HIV-infected subjects, and 3) understand where infected a4b7- expressing CD4+ T cells reside in the early stages of infection. The interaction between gp120 and a4b7 holds the potential to impact the design of both vaccines as well as therapeutic strategies aimed at reducing viral reservoirs. Using an SIV/rhesus macaque model and immune PET/CT imaging, we have gained new insights into the role of this important subset of CD4+ T cells in the early stages of HIV infection.

  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 #
1ZIAAI000883-18
Application #
9786347
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
18
Fiscal Year
2018
Total Cost
Indirect Cost

  Institution

Name
Niaid Extramural Activities
Department
Type
DUNS #
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State
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  Publications

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:
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
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
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

Showing the most recent 10 out of 43 publications