A nonneutralizing anti-HIV Type 1 antibody turns into a broad neutralizing antibody when expressed on the surface of HIV type 1-susceptible cells. II. Inhibition of HIV type 1 captured and transferred by DC-SIGN.
Previously, we demonstrated that the expression of a nonneutralizing human anti-HIV-1 gp41 scFv on the surface of HIV-1-susceptible cells markedly inhibits HIV-1 replication and HIV-1 envelope-mediated cell-cell fusion. The inhibition is at the level of viral entry, specific for the HIV-1 envelope, and independent of virus tropism. In the previous studies, cell-free viruses of laboratory-adapted HIV-1 strains from subtype B were used to infect human CD4 T cell lines. To further test the effectiveness of this membrane-bound scFv (m-scFv) on HIV-1 infection, in this study, we carried out experiments to determine whether the m-scFv can neutralize infection of primary isolates from various HIV-1 subtypes and whether the m-scFv can neutralize HIV-1 captured and transferred by DC-SIGN on the surface of monocytic cell lines or DCs. We demonstrated that the m-scFv markedly inhibits primary isolates derived from various subtypes and significantly blocks HIV-1 captured and transferred by DC-SIGN on monocytic cell lines and on human DCs. Therefore, a nonneutralizing antibody acts as a broad neutralizing antibody when expressed on the cell surface, which significantly inhibits infection of both cell-free and DC-SIGN-captured and transferred virus. Our studies further point out the potential use of m-scFv as a inhibitor against HIV-1 transmission as well as a tool to dissect the mechanism of HIV-1 entry via DC-SIGN capture and transfer to CD4 T cells.
Lee
Seung-Jae
SJ
Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, Texas 78249, USA.
Arora
Reetakshi
R
Bull
Lara M
LM
Arduino
Roberto C
RC
Garza
Laura
L
Allan
Jonathan
J
Kimata
Jason T
JT
Zhou
Paul
P
D000917:Antibody Formation; D015815:Cell Adhesion Molecules / Q000502:physiology*; D018929:Cell Culture Techniques; D002460:Cell Line / Q000276:immunology / Q000821:virology; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000276:immunology* / Q000378:metabolism; D037181:Lectins, C-Type / Q000502:physiology*; D009000:Monocytes / Q000276:immunology / Q000821:virology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000502:physiology*; D014779:Virus Replication / Q000276:immunology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D007135:Immunoglobulin Variable Region; D037181:Lectins, C-Type; D011947:Receptors, Antigen, B-Cell; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin