A critical role for CD63 in HIV replication and infection of macrophages and cell lines.
HIV infection typically involves interaction of Env with CD4 and a chemokine coreceptor, either CCR5 or CXCR4. Other cellular factors supporting HIV replication have also been characterized. We previously demonstrated a role for CD63 in early HIV infection events in macrophages via inhibition by anti-CD63 antibody pretreatment. To confirm the requirement for CD63 in HIV replication, we decreased CD63 expression using CD63-specific short interfering RNAs (siRNA), and showed inhibition of HIV replication in macrophages. Surprisingly, pretreatment with CD63 siRNA not only silenced CD63 expression by 90%, but also inhibited HIV-1 replication in a cultured cell line (U373-MAGI) which had been previously shown to be insensitive to CD63 monoclonal antibody inhibition. Although the anti-CD63 antibody was previously shown to inhibit early HIV infection events only in macrophages, we now show a potential role for CD63 in later HIV replication events in macrophages and cell lines. Further delineation of the role of CD63 in HIV replication may lead to development of novel therapeutic compounds.
Chen
Hui
H
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555-0435, USA.
Dziuba
Natallia
N
Friedrich
Brian
B
von Lindern
Jana
J
Murray
James L
JL
Rojo
Daniel R
DR
Hodge
Thomas W
TW
O'Brien
William A
WA
Ferguson
Monique R
MR
D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D015536:Down-Regulation; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000821:virology; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D060149:Tetraspanin 30; D014162:Transfection; D014779:Virus Replication / Q000276:immunology / Q000502:physiology*
D015703:Antigens, CD; C554586:CD63 protein, human; D010980:Platelet Membrane Glycoproteins; D034741:RNA, Small Interfering; D060149:Tetraspanin 30