CXCR4 is down-regulated in cells infected with the CD4-independent X4 human immunodeficiency virus type 1 isolate m7NDK.
Macrophages and T cells infected in vitro with CD4-dependent human immunodeficiency virus type 1 (HIV-1) isolates have reduced levels of CD4 protein, a phenomenon involved in retroviral interference. We have previously characterized the first CD4-independent HIV-1 X4 isolate m7NDK, which directly interacts with CXCR4 through its mutated gp120. We thus investigate CXCR4 expression in cells infected with this m7NDK CXCR4-dependent HIV-1 mutant. We present evidence of the down-regulation of CXCR4 membrane expression in CD4-positive or -negative cells chronically infected with the HIV-1 m7NDK, a phenomenon which is not observed in the CD4-dependent HIV-1 NDK parental strain. This down-regulation of CXCR4 was demonstrated by fluorescence-activated cell sorter analysis and was confirmed by the absence of CXCR4 functionality in m7NDK-infected cells, independently of the presence of CD4 protein. Furthermore, a drastic reduction of the intracellular level of CXCR4 protein was also observed. Reduced levels of CXCR4 mRNA transcripts were found in m7NDK-infected HeLa and CEM cells, reduced levels that could not be attributed to a reduced stability of CXCR4 mRNA. Down-regulation of CXCR4 on m7NDK-infected cells may thus be explained by transcriptional regulation.
Valente
S T
ST
INSERM Unité 380 Laboratoire de Pathologie et Genétique Expérimentales, Institut Cochin de Génétique Moléculaire, 75014 Paris, France. valente@cochin.inserm.fr
Chanel
C
C
Dumonceaux
J
J
Olivier
R
R
Marullo
S
S
Briand
P
P
Hazan
U
U
D015704:CD4 Antigens / Q000502:physiology*; D002460:Cell Line; D015536:Down-Regulation; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D012333:RNA, Messenger / Q000032:analysis; D019718:Receptors, CXCR4 / Q000032:analysis* / Q000235:genetics / Q000502:physiology
D015704:CD4 Antigens; D012333:RNA, Messenger; D019718:Receptors, CXCR4