Production of HIV-1 by human B cells infected in vitro: characterization of an EBV genome-negative B cell line chronically synthetizing a low level of HIV-1 after infection.
Human immunodeficiency virus type 1 (HIV-1) has tropism for helper T lymphocytes and cells of the monocyte/ macrophage lineages. HIV-1 can also infect other cell types, including B cells. We show here that 10% of fresh circulating B cells from HIV-1-seronegative donors (i) express the CD4 receptor and CCR5 and CXCR4, two recently described coreceptors for HIV-1 and (ii) are permissive to HIV-1 with de novo proviral DNA integration following ex vivo infection by either SI (syncytium-inducing) or NSI (non-syncytium-inducing) isolates. To get further information on the interaction between HIV and B cells, the susceptibility of several EBV-positive or -negative B cell lines to infection by SI and NSI isolates was checked. Following infection of an EBV- CD4+ CXCR4+ CCR5- B cell line (DG75) by an SI HIV-1 isolate, we obtained a cell line which chronically produced low-level infectious HIV-1 for 2 years (HIV-DG75). Immunocytochemical data, combined with in situ PCR data, established that HIV-DG75 cells consist of at least three populations uninfected cells, infected virus-producing cells, and infected but nonproducing cells. Moreover, HIV-DG75 cells which express p24 antigen do not go into apoptosis, contrary to T lymphocytes. We infer from these results that B cells could constitute a reservoir of infectious virus in infected patients.
Fritsch
L
L
Laboratoire de Microbiologie, Hôpital Rothschild, Paris, France.
Marechal
V
V
Schneider
V
V
Barthet
C
C
Rozenbaum
W
W
Moisan-Coppey
M
M
Coppey
J
J
Nicolas
J C
JC
D018941:Antigens, CD19 / Q000378:metabolism; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology*; D001483:Base Sequence; D015704:CD4 Antigens / Q000378:metabolism; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D016679:Genome, Viral; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D066298:In Vitro Techniques; D016133:Polymerase Chain Reaction; D019713:Receptors, CCR5 / Q000235:genetics; D019718:Receptors, CXCR4 / Q000235:genetics; D014779:Virus Replication
D018941:Antigens, CD19; D015704:CD4 Antigens; D017931:DNA Primers; D004279:DNA, Viral; D019713:Receptors, CCR5; D019718:Receptors, CXCR4