Coassembly and complementation of Gag proteins from HIV-1 and HIV-2, two distinct human pathogens.
Approximately one million people in the world are dually infected with both HIV-1 and HIV-2. To identify potential interactions between these two human pathogens, we examined whether HIV-1 and HIV-2 Gag proteins can coassemble and functionally complement each other. We generated HIV-1- and HIV-2-based vectors with mutations in Gag; compared with wild-type vectors, these mutants had drastically decreased viral titers. Coexpression of the mutant HIV-1 and HIV-2 Gag could generate infectious viruses; furthermore, heterologous complementation in certain combinations showed efficiency similar to homologous complementation. Additionally, we used bimolecular fluorescence complementation analysis to directly demonstrate that HIV-1 and HIV-2 Gag can interact and coassemble. Taken together, our results indicate that HIV-1 and HIV-2 Gag polyproteins can coassemble and functionally complement each other during virus replication; to our knowledge, this is the first demonstration of its kind. These studies have important implications for AIDS treatment and the evolution of primate lentiviruses.
Boyko
Vitaly
V
HIV Drug Resistance Program, National Cancer Institute, SAIC-Frederick, Inc., NCI-Frederick, Frederick, Maryland 21702, USA.
Leavitt
Maria
M
Gorelick
Robert
R
Fu
William
W
Nikolaitchik
Olga
O
Pathak
Vinay K
VK
Nagashima
Kunio
K
Hu
Wei-Shau
WS
D015683:Gene Products, gag / Q000096:biosynthesis* / Q000235:genetics*; D005816:Genetic Complementation Test; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism*; D015498:HIV-2 / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D014779:Virus Replication / Q000235:genetics
D015683:Gene Products, gag