Prestimulation of CD2 confers resistance to HIV-1 latent infection in blood resting CD4 T cells

Sijia He; Jia Guo; Yajing Fu; Mark Spear; Chaolong Qin; Shuai Fu; Zongqiang Cui; Wenwen Jin; Xuehua Xu; Wanjun Chen; Hong Shang; Yuntao Wu

doi:10.1016/j.isci.2021.103305

Prestimulation of CD2 confers resistance to HIV-1 latent infection in blood resting CD4 T cells

iScience. 2021 Oct 16;24(11):103305. doi: 10.1016/j.isci.2021.103305. eCollection 2021 Nov 19.

Authors

Sijia He^{1

2}, Jia Guo², Yajing Fu^{1

2}, Mark Spear², Chaolong Qin¹, Shuai Fu¹, Zongqiang Cui², Wenwen Jin³, Xuehua Xu⁴, Wanjun Chen³, Hong Shang¹, Yuntao Wu²

Affiliations

¹ NHC Key Laboratory of AIDS Immunology (China Medical University), National Clinical Research Center for Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China.
² Center for Infectious Disease Research, School of Systems Biology, George Mason University, Manassas, VA 20110, USA.
³ Mucosal Immunology Section, NIDCR, NIH, Bethesda, MD 20892, USA.
⁴ Chemotaxis Signal Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Disease, NIH, Twinbrook Facility, Rockville, MD 20852, USA.

Abstract

HIV-1 infects blood CD4 T cells through the use of CD4 and CXCR4 or CCR5 receptors, which can be targeted through blocking viral binding to CD4/CXCR4/CCR5 or virus-cell fusion. Here we describe a novel mechanism by which HIV-1 nuclear entry can also be blocked through targeting a non-entry receptor, CD2. Cluster of differentiation 2 (CD2) is an adhesion molecule highly expressed on human blood CD4, particularly, memory CD4 T cells. We found that CD2 ligation with its cell-free ligand LFA-3 or anti-CD2 antibodies rendered blood resting CD4 T cells highly resistant to HIV-1 infection. We further demonstrate that mechanistically, CD2 binding initiates competitive signaling leading to cofilin activation and localized actin polymerization around CD2, which spatially inhibits HIV-1-initiated local actin polymerization needed for viral nuclear migration. Our study identifies CD2 as a novel target to block HIV-1 infection of blood resting T cells.

Keywords: Immune response; Immunology; Virology.