Inhibitory role of CXCR4 glycan in CD4-independent X4-tropic human immunodeficiency virus type 1 infection and its abrogation in CD4-dependent infection.
CXCR4 functions as an infection receptor of X4 human immunodeficiency virus type 1 (HIV-1) . CXCR4 is glycosylated at the N-terminal extracellular region, which is important for viral envelope (Env) protein binding. We compared the effects of CXCR4 glycan on the CD4-dependent and -independent infections in human cells by X4 viruses. We found that transduction mediated by Env proteins of CD4-independent HIV-1 strains increased up to 5.5-fold in cells expressing unglycosylated CXCR4, suggesting that the CXCR4 glycan inhibits CD4-independent X4 virus infection. Co-expression of CD4 on the target cell surface or pre-incubation of virus particles with soluble CD4 abrogates the glycan-mediated inhibition of X4 virus infection, suggesting that interaction of Env protein with CD4 counteracts the inhibition. These findings indicate that it will be advantageous for X4 HIV-1 to remain CD4-dependent. A structural model that explains the glycan-mediated inhibition is discussed.
Kubo
Yoshinao
Y
Department of AIDS Research, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
Yokoyama
Masaru
M
Laboratory of Viral Genomics, Center for Pathogen Genomics, National Institute of Infectious Diseases, Tokyo, Japan.|Department of AIDS Research, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
Yoshii
Hiroaki
H
Department of AIDS Research, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
Mitani
Chiho
C
Department of AIDS Research, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
Tominaga
Chika
C
Department of AIDS Research, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
Tanaka
Yuetsu
Y
Department of Immunology, Graduate School and Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
Sato
Hironori
H
Laboratory of Viral Genomics, Center for Pathogen Genomics, National Institute of Infectious Diseases, Tokyo, Japan.|Department of AIDS Research, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
Yamamoto
Naoki
N
Department of Molecular Virology, Tokyo Medical and Dental University, Tokyo, Japan.|AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.|Department of AIDS Research, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
D002460:Cell Line; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008958:Models, Molecular; D011134:Polysaccharides / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D019718:Receptors, CXCR4 / Q000737:chemistry* / Q000502:physiology*; D014161:Transduction, Genetic; D053585:Virus Attachment
D011134:Polysaccharides; D019718:Receptors, CXCR4