Abstract

Critical events in HIV pathogenesis, including the establishment of persistent viral reservoirs occur shortly after infection. Yet the earliest events following mucosal transmission are not well defined. Understanding these events may provide important information regarding the design of an HIV vaccine. They may also provide new strategies to diminish the size of the viral reservoir. We are testing the hypothesis that HIV gp120 interactions with integrin a4b7 represent an important aspect of HIV transmission and pathogenesis. Integrin a4b7 is not an entry receptor, yet cells expressing this receptor are preferentially infected. The way this occurs is not yet understood. However, the interaction between gp120 and a4b7 holds the potential to impact the design of both vaccines and therapeutic strategies that reduce viral reservoirs. Using an SIV/rhesus macaque model we are investigating the utility of an anti- a4b7 monoclonal antibody in preventing infection. We are also evaluating the utility of this antibody as a therapeutic agent for the treatment of HIV disease.

  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 #
1ZIAAI000883-17
Application #
9563884
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
17
Fiscal Year
2017
Total Cost
Indirect Cost

  Institution

Name
Niaid Extramural Activities
Department
Type
DUNS #
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State
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  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:
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