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
Affiliations
Sijia He
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; Center for Infectious Disease Research, School of Systems Biology, George Mason University, Manassas, VA 20110, USA
Jia Guo
Center for Infectious Disease Research, School of Systems Biology, George Mason University, Manassas, VA 20110, USA
Yajing Fu
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; Center for Infectious Disease Research, School of Systems Biology, George Mason University, Manassas, VA 20110, USA
Mark Spear
Center for Infectious Disease Research, School of Systems Biology, George Mason University, Manassas, VA 20110, USA
Chaolong Qin
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
Shuai Fu
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
Zongqiang Cui
Center for Infectious Disease Research, School of Systems Biology, George Mason University, Manassas, VA 20110, USA
Wenwen Jin
Mucosal Immunology Section, NIDCR, NIH, Bethesda, MD 20892, USA
Xuehua Xu
Chemotaxis Signal Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Disease, NIH, Twinbrook Facility, Rockville, MD 20852, USA
Wanjun Chen
Mucosal Immunology Section, NIDCR, NIH, Bethesda, MD 20892, USA
Hong Shang
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; Corresponding author
Yuntao Wu
Center for Infectious Disease Research, School of Systems Biology, George Mason University, Manassas, VA 20110, USA; Corresponding author
Summary: 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.
