Sheila Nabweyambo, PhD, MSc, BBLT
SHEILA NABWEYAMBO
Nominated From: University of Minnesota
Research Site: Makerere University
Research Area: HIV
Primary Mentor: Joshua Rhein, PhD
Research Project
Investigating the relationship of α4β7 Co-expression Levels with Susceptibility of Cervical CD4⁺ T Cells to HIV Entry
The integrin α4β7 is a key mucosal homing receptor that marks CD4⁺ T cells with heightened susceptibility to HIV infection, particularly in the female genital tract. While α4β7⁺ CD4⁺ T cells have been identified as preferential HIV targets, the relationship between the α4β7 co-expression levels and HIV infection susceptibility in cervical T cells remains unclear. Objective: This study aims to determine how α4β7 co-expression levels influence CD4⁺ T cell vulnerability to HIV Methods: CEM CD4⁺ T cells will be engineered with independently tunable α4 and β7 subunits to construct a two-dimensional α4×β7 expression matrix and identify co-expression thresholds. CCR5-tropic HIV reporter viruses will be used to quantify infection via flow cytometry, and response-surface modeling will define the optimal co-expression zone. Primary cervical CD4⁺ T cells from HIV-negative women will be used to validate the experimental findings.
Research Significance
This study will provide insights into the role of different levels of α4 and β7 expression in HIV transmission at the cervix. By defining optimal expression thresholds, it will provide foundational insights for integrin-targeted prevention strategies, potentially accelerating translational interventions in both high-burden settings. Beyond HIV, these findings will inform future investigations into maternal health, as α4β7-mediated mucosal immune pathways may influence pregnancy outcomes such as preeclampsia, fetal growth restriction, and stillbirth.
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