Inhibition of human immunodeficiency virus type 1 integrase by the Fab fragment of a specific monoclonal antibody suggests that different multimerization states are required for different enzymatic functions.
We have characterized a murine monoclonal antibody (MAb 35), which was raised against human immunodeficiency virus type 1 (HIV-1) integration protein (IN), and the corresponding Fab 35. Although MAb 35 does not inhibit HIV-1 IN, Fab 35 does. MAb 35 (and Fab 35) binds to an epitope in the C-terminal region of HIV-1 IN. Fab 35 inhibits 3'-end processing, strand transfer, and disintegration; however, DNA binding is not affected. The available data suggest that Fab 35 inhibits enzymatic activities of IN by interfering with the ability of IN to form multimers that are enzymatically active. This implies that the C-terminal region of HIV-1 IN participates in interactions that are essential for the multimerization of IN. Titration of the various IN-mediated enzymatic activities suggests that different degrees of multimerization are required for different activities of HIV-1 IN.
Barsov
E V
EV
ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201, USA.
Huber
W E
WE
Marcotrigiano
J
J
Clark
P K
PK
Clark
A D
AD
Arnold
E
E
Hughes
S H
SH
D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D003001:Cloning, Molecular; D004254:DNA Nucleotidyltransferases / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D004279:DNA, Viral / Q000378:metabolism; D018604:Epitope Mapping; D015483:HIV Antibodies / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000201:enzymology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000235:genetics / Q000276:immunology*; D019426:Integrases; D008969:Molecular Sequence Data; D011485:Protein Binding; D013329:Structure-Activity Relationship; D016662:Virus Integration
D000911:Antibodies, Monoclonal; D004279:DNA, Viral; D015483:HIV Antibodies; D007140:Immunoglobulin Fab Fragments; D004254:DNA Nucleotidyltransferases; D019426:Integrases