Characterization of the effects of aryl-azido compounds and UVA irradiation on the viral proteins and infectivity of human immunodeficiency virus type 1.
Hydrophobic UV-activatable compounds have been shown to partition into the hydrophobic region of biological membranes to selectively label transmembrane proteins, and to inactivate enveloped viruses. Here, we analyze various UV-activatable azido- and iodo-based hydrophobic compounds for their ability to inactivate a model-enveloped virus, human immunodeficiency virus (HIV-1 MN). Treatment of HIV-1 with 1,5-diazidonapthalene (DAN), 1-iodo, 5-azidonaphthalene (INA), 1-azidonaphthalene (AzNAP) or 4,4'-diazidobiphenyl (DABIPH) followed by UVA irradiation for 2 min resulted in complete viral inactivation, whereas treatment using analogous non-azido-containing controls had no effect. Incorporation of an azido moiety within these hydrophobic compounds to promote photoinduced covalent reactions with proteins was found to be the primary mechanism of viral inactivation for this class of compounds. Prolonged UVA irradiation of the virus in the presence of these azido compounds resulted in further modifications of viral proteins, due to the generation of reactive oxygen species, leading to aggregation as visualized via Western blot analysis, providing additional viral modifications that may inhibit viral infectivity. Furthermore, inactivation using these compounds resulted in the preservation of surface antigenic structures (recognized by neutralizing antibodies b12, 2g12 and 4e10), which is favorable for the creation of vaccines from these inactivated virus preparations.
Belanger
Julie M
JM
Center for Cancer Research Nanobiology Program, NCI-Frederick, Frederick, MD, USA.
Raviv
Yossef
Y
Viard
Mathias
M
Jason de la Cruz
Michael
M
Nagashima
Kunio
K
Blumenthal
Robert
R
D000998:Antiviral Agents / Q000494:pharmacology*; D001386:Azides / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D015497:HIV-1 / Q000187:drug effects* / Q000472:pathogenicity / Q000528:radiation effects*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008855:Microscopy, Electron, Scanning; D015394:Molecular Structure; D014466:Ultraviolet Rays; D014764:Viral Proteins / Q000187:drug effects* / Q000528:radiation effects*
D000998:Antiviral Agents; D001386:Azides; D014764:Viral Proteins