Sensitivity of HIV type 1 primary isolates to human anti-CD40 antibody-mediated suppression is related to coreceptor use.
The effect of CD40 ligation on infection by HIV-1 primary isolates with different R5 phenotypes was evaluated with a novel set of anti-CD40 monoclonal antibodies originating from a human phage display library. Five human monoclonal anti-CD40 antibodies of IgG1 subtype characterized by the ability to activate B cells via CD40 were tested for induction of the CC-chemokines RANTES and MIP-1alpha and inhibition of HIV-1 replication in primary monocyte-derived macrophages (MDM). All activating anti-CD40 antibodies were able to induce CC-chemokines in MDM. We chose the most potent antibody, clone B44, for further experiments. This antibody had a suppressive effect on HIV-1 isolates of the R5 phenotype with limited use of CCR5/CXCR4 chimeric receptors. In comparison, HIV-1 isolates with broader use of CCR5/CXCR4 chimeric receptors or with CXCR4 use were less sensitive to anti-CD40-induced suppression. The results indicate that HIV-1 replication is inhibited by human anti-CD40 monoclonal antibodies through the mechanism of CC-chemokine induction. This effect is thus restricted to HIV-1 isolates sensitive to inhibition by CC-chemokines.
Abayneh
Sisay A
SA
Division of Medical Microbiology, Department of Laboratory Medicine, Lund University, Lund, Sweden.
Ellmark
Peter
P
Karlsson
Ulf
U
Andersson
Henrik
H
Borrebaeck
Carl A K
CA
Karlsson
Ingrid
I
Fenyö
Eva Maria
EM
D000911:Antibodies, Monoclonal / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology*; D002478:Cells, Cultured; D054405:Chemokine CCL3 / Q000096:biosynthesis; D018946:Chemokine CCL5 / Q000096:biosynthesis; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D015497:HIV-1 / Q000254:growth & development* / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000821:virology*; D019713:Receptors, CCR5 / Q000276:immunology; D014779:Virus Replication / Q000276:immunology
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D054405:Chemokine CCL3; D018946:Chemokine CCL5; D016655:HIV Core Protein p24; D007074:Immunoglobulin G; D019713:Receptors, CCR5; C514799:p24 protein, Human Immunodeficiency Virus Type 1