Biology Reference
In-Depth Information
monocyte-derived DC were productively infected at low levels by M-tropic
HIV-1 in contrast to T-tropic HIV-1 ( Delgado et al., 1998), even though both
CCR5 and CXCR4 were expressed; upon maturation, the cells lost their ability
to replicate HIV-1 but were still e½cient in transmitting both M- and T-tropic
viruses to activated T cells, demonstrating that replication is not necessary for
HIV-1 transmission. The capacity to support HIV-1 replication depends on the
maturation state of DC. Immature DC cultured from cord blood CD34 cells
were permissive for M-tropic HIV-1 but not for T-tropic HIV-1, in accordance
with the presence of CCR5 and the absence of CXCR4; after maturation, DC
became permissive for T-tropic HIV-1 resulting from up regulation of CXCR4,
although no productive infection occurred (Canque et al., 1996). Collectively,
these experiments demonstrate that HIV-1 entry into DC can be detected but
that it does not necessarily lead to a productive infection of these cells in the
absence of T cells. The reasons for these discrepancies are still unclear, but they
may re¯ect di¨erences in DC isolation procedures and culture methods. The
purity of the DC fractions used is essential, as low levels of contaminating
T cells lead to severely compromised results regarding productive infection.
Sensitivity of the detection method and the virus concentration used in the DC
infection are also important variables. Moreover, HIV-1 susceptibility has been
shown to be dependent on DC origin and maturation state (Canque et al., 1996;
Delgado et al., 1998). Expression of CD4 di¨ers greatly among various DC
populations and expression of CCR5 and CXCR4 is strongly dependent on the
maturation stage of DC.
Similar results were obtained with DC isolated from tissues. Skin-derived
DC were not infected by HIV-1 in the absence of T cells, whereas a vigorous
productive infection occurred when conjugates of DC with T cells were pulsed
with HIV-1 (Ayehunie et al., 1995; Pope et al., 1994, 1995). Similarly, pulsing
of isolated blood DC did not result in a productive infection (Cameron et al.,
1992b; Weissman et al., 1995a). HIV-1-pulsed blood DC bound HIV-1 on their
cell surface and e½ciently enhanced infection of resting CD4 T cells ( Weiss-
man et al., 1995b).
Despite these con¯icting reports, it is clear that DC are able, by the action of
DC-SIGN, to capture HIV-1 at mucosal sites. DC might mediate viral entry to
an extent during HIV-1 capture, depending on the expression of CD4, CCR5,
and CXCR4, although this is a rather ine½cient process compared with T cells.
The observation that expression of CCR5 on DC is di¨erent between in vitro-
and in vivo-derived DC (Geijtenbeek et al., 2000a) demonstrates that data ob-
tained from HIV-1 infection of in vitro derived DC do not necessarily re¯ect
the in vivo situation.
DC CAPTURE HIV-1 AND EFFICIENTLY TRANSMIT HIV-1 TO
T CELLS
In contrast to the varying results obtained for the direct infection of DC with
HIV-1, there is substantial evidence that all types of DC pulsed with HIV-1 in
Search WWH ::




Custom Search