The role of conventional antibodies targeting the CD4 binding site and CD4-induced epitopes in the control of HIV-1 CRF01_AE viruses

Win Thida; Takeo Kuwata; Yosuke Maeda; Tetsu Yamashiro; Giang Van Tran; Kinh Van Nguyen; Masafumi Takiguchi; Hiroyuki Gatanaga; Kazuki Tanaka; Shuzo Matsushita

doi:10.1016/j.bbrc.2018.11.063

The role of conventional antibodies targeting the CD4 binding site and CD4-induced epitopes in the control of HIV-1 CRF01_AE viruses

Biochem Biophys Res Commun. 2019 Jan 1;508(1):46-51. doi: 10.1016/j.bbrc.2018.11.063. Epub 2018 Nov 20.

Authors

Affiliations

¹ Center for AIDS Research, Kumamoto University, Kumamoto, Japan.
² Center for AIDS Research, Kumamoto University, Kumamoto, Japan. Electronic address: tkuwata@kumamoto-u.ac.jp.
³ Department of Microbiology, Kumamoto University, Kumamoto, Japan.
⁴ Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
⁵ National Hospital of Tropical Diseases, Dong Da District, Hanoi, Viet Nam.
⁶ AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan.

PMID: 30470571
DOI: 10.1016/j.bbrc.2018.11.063

Abstract

HIV-1 CRF01_AE viruses are highly prevalent in Southeast Asia. However, vulnerability sites in Env of CRF01_AE viruses have not been investigated sufficiently. We examined the sensitivity of CRF01_AE viruses from Japan and Vietnam, together with subtype B viruses from Japan, to neutralization and Fc-mediated signaling. Neutralization coverage of broadly neutralizing antibodies (bnAbs), 2G12 and b12, was significantly low against CRF01_AE viruses, compared with subtype B viruses. In contrast, the conventional antibody targeting the CD4 binding site (CD4bs), 49G2, showed better neutralization and Fc-mediated signaling activities against CRF01_AE viruses than subtype B viruses. Fc-mediated signaling activity of anti-CD4 induced (CD4i) antibody, 4E9C, was also detected against CRF01_AE viruses more than subtype B viruses. These results suggest that conventional antibodies against CD4bs and CD4i may play an important role in the control of CRF01_AE viruses.

Keywords: Antibody; CRF01_AE; Fc-mediated signaling; HIV-1; Neutralization.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Monoclonal / immunology
Antibodies, Neutralizing / immunology
Binding Sites / immunology
CD4 Antigens / immunology
Epitopes / immunology
HIV Antibodies / immunology
HIV Infections / immunology*
HIV Infections / virology*
HIV-1 / classification*
HIV-1 / genetics
HIV-1 / immunology*
Humans
Neutralization Tests
Receptors, IgG / immunology
Signal Transduction / immunology
env Gene Products, Human Immunodeficiency Virus / genetics

Substances

Antibodies, Monoclonal
Antibodies, Neutralizing
CD4 Antigens
Epitopes
FCGR3A protein, human
HIV Antibodies
Receptors, IgG
env Gene Products, Human Immunodeficiency Virus