Ezrin, Radixin, and Moesin (ERM) proteins function as pleiotropic regulators of human immunodeficiency virus type 1 infection.
Ezrin, radixin, and moesin (ERM) proteins supply functional linkage between integral membrane proteins and cytoskeleton in mammalian cells to regulate membrane protein dynamisms and cytoskeleton rearrangement. To assess potential role of the ERM proteins in HIV-1 lifecycle, we examined if suppression of ERM function in human cells expressing HIV-1 infection receptors influences HIV-1 envelope (Env)-mediated HIV-1-vector transduction and cell-cell fusion. Expression of an ezrin dominant negative mutant or knockdown of ezrin, radixin, or moesin with siRNA uniformly decreased transduction titers of HIV-1 vectors having X4-tropic Env. In contrast, transduction titers of R5-tropic Env HIV-1 vectors were decreased only by radixin knockdown: ezrin knockdown had no detectable effects and moesin knockdown rather increased transduction titer. Each of the ERM suppressions had no detectable effects on cell surface expression of CD4, CCR5, and CXCR4 or VSV-Env-mediated HIV-1 vector transductions. Finally, the individual knockdown of ERM mRNAs uniformly decreased efficiency of cell-cell fusion mediated by X4- or R5-tropic Env and HIV-1 infection receptors. These results suggest that (i) the ERM proteins function as positive regulators of infection by X4-tropic HIV-1, (ii) moesin additionally functions as a negative regulator of R5-tropic HIV-1 virus infection at the early step(s) after the membrane fusion, and (iii) receptor protein dynamisms are regulated differently in R5- and X4-tropic HIV-1 infections.
Kubo
Yoshinao
Y
Department of AIDS Research, Institute of Tropical Medicine, Nagasaki University, Nagasaki, National Institute of Infectious Diseases, Tokyo, Japan. yoshinao@net.nagasaki-u.ac.jp
Yoshii
Hiroaki
H
Kamiyama
Haruka
H
Tominaga
Chika
C
Tanaka
Yuetsu
Y
Sato
Hironori
H
Yamamoto
Naoki
N
D015704:CD4 Antigens / Q000096:biosynthesis; D002459:Cell Fusion; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000502:physiology*; D020868:Gene Silencing; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology*; D008840:Microfilament Proteins / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D019713:Receptors, CCR5 / Q000096:biosynthesis; D019718:Receptors, CXCR4 / Q000096:biosynthesis; D014161:Transduction, Genetic; D053586:Virus Internalization; D000099149:Ezrin
D015704:CD4 Antigens; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D034741:RNA, Small Interfering; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D000099149:Ezrin; C527276:CXCR4 protein, human; C071058:moesin; C071776:radixin