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Blood, Vol. 96 No. 1 (July 1), 2000:
pp. 41-49
Expression and coreceptor activity of STRL33/Bonzo on primary
peripheral blood lymphocytes
Matthew Sharron,
Stefan Pöhlmann,
Ken Price,
Elias Lolis,
Monica Tsang,
Frank Kirchhoff,
Robert W. Doms, and
Benhur Lee
From the University of Pennsylvania, Department of Pathology and
Laboratory Medicine, Philadelphia, PA; the Institute for Clinical and
Molecular Virology, University of Erlangen-Nürnberg,
Schlo garten, Erlangen, Germany; R&D Systems,
Minneapolis, MN; and the Department of Pharmacology, Yale University,
New Haven, CT.
CCR5 and CXCR4 are the major coreceptors that mediate human
immunodeficiency virus 1 (HIV-1) infection, while most simian immunodeficiency virus (SIV) isolates use CCR5. A number of alternative coreceptors can also mediate infection of some virus strains in vitro,
although little is known about their in vivo relevance. Therefore, we characterized the expression pattern and coreceptor activity of one of these alternative coreceptors, STRL33/Bonzo, using a
newly developed monoclonal antibody. In addition to being highly
expressed (approximately 1000-7000 STRL33 ABS [antibody binding
sites]) on specific subsets of natural killer cells
(CD3 /CD16/low/CD56+ and
CD3/CD16low/CD56) and
CD19+ B lymphocytes (approximately 300-5000 STRL33 ABS),
STRL33 was expressed at levels sufficient to support virus infection on
freshly isolated, truly naive
CD4+/CD45RA+/CD62L+
cells (6000-11 000 ABS). STRL33 expression on peripheral blood mononuclear cells (PBMCs) was increased by mitogenic stimulation (OKT3/IL-2 [interleukin-2] had a greater effect than
phytohemaglutinin (PHA)/IL-2), but it was dramatically decreased
upon Ficoll purification. Infection of CCR5 human
peripheral blood lymphocytes (PBLs) showed that 2 different SIV
envelope (Env) proteins mediated entry into STRL33+
cells. More importantly, the preferential infection of
STRL33+ cells in CCR5 PBLs by an
R5/X4/STRL33 HIV-1 maternal isolate in the presence of a
potent CXCR4 antagonist (AMD3100) suggests that STRL33 can be used as a
coreceptor by HIV-1 on primary cells. Rhesus macaque (rh) STRL33 was
used less efficiently than human STRL33 by the majority of SIV Env
proteins tested despite similar levels of expression, thereby making it
less likely that STRL33 is a relevant coreceptor in the rhesus macaque
system. In summary, the expression pattern and coreceptor activity of
STRL33 suggest its involvement in trafficking of tumor-infiltrating
lymphocytes and indicate that STRL33 may be a relevant coreceptor in vivo.
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