Azurin, Plasmodium falciparum malaria and HIV/AIDS: inhibition of parasitic and viral growth by Azurin.
Azurin, a member of a family of copper-containing proteins involved in electron transfer called cupredoxins, demonstrates structural features similar to the variable domains of the immunoglobulin superfamily members. An azurin-like protein called Laz with an additional N-terminal 39 amino acid peptide known as H.8 epitope is present on the surface of gonnococci and meningococci. We demonstrate that azurin, Laz and H.8-azurin can bind to the C-terminal cleavage product MSP1-19 of merozoite surface protein 1 (MSP1) of the malarial parasite Plasmodium falciparum and significantly reduce parasitemia. Azurin and Laz also bound strongly to HIV-1 gp120. Interestingly, azurin could not only bind to gp120 but also to the dendritic cell-specific adhesion receptor DC-SIGN, mimicking the functionality of the intercellular adhesion molecule ICAM-3 with which it also binds avidly. Furthermore, these three proteins significantly suppressed HIV-1 growth in peripheral blood mononuclear cells and such suppression appeared to be occurring at an entry stage in the infection process. The presence of both antimalarial and antiretroviral activity in azurin, H.8-azurin and Laz makes these proteins, or peptides derived from them, potential therapeutic agents in the treatment of malaria, HIV-1 infections or coinfections with both P. falciparum and HIV-1.
Chaudhari
Anita
A
Department of Microbiology & Immunology, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
Fialho
Arsenio M
AM
Ratner
Deena
D
Gupta
Phalguni
P
Hong
Chang Soo
CS
Kahali
Soumen
S
Yamada
Tohru
T
Haldar
Kasturi
K
Murphy
Sean
S
Cho
Wonhwa
W
Chauhan
Virander S
VS
Das Gupta
Tapas K
TK
Chakrabarty
Ananda M
AM
D000163:Acquired Immunodeficiency Syndrome / Q000821:virology*; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001400:Azurin / Q000378:metabolism*; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D004912:Erythrocytes / Q000469:parasitology; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015497:HIV-1 / Q000254:growth & development* / Q000502:physiology*; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry / Q000276:immunology; D037181:Lectins, C-Type / Q000378:metabolism; D016778:Malaria, Falciparum / Q000469:parasitology*; D020066:Merozoite Surface Protein 1 / Q000378:metabolism; D009343:Neisseria / Q000737:chemistry / Q000276:immunology; D018512:Parasitemia; D010963:Plasmodium falciparum / Q000254:growth & development* / Q000502:physiology*; D011485:Protein Binding; D011550:Pseudomonas aeruginosa / Q000737:chemistry / Q000276:immunology; D011956:Receptors, Cell Surface / Q000378:metabolism; D020349:Surface Plasmon Resonance; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D000942:Antigens, Bacterial; D001400:Azurin; D001425:Bacterial Outer Membrane Proteins; D015815:Cell Adhesion Molecules; D015699:HIV Envelope Protein gp120; D007136:Immunoglobulins; D037181:Lectins, C-Type; D020066:Merozoite Surface Protein 1; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C055700:H.8 protein (Neisseria)