Selective transmission of R5-tropic HIV type 1 from dendritic cells to resting CD4+ T cells.
In an in vitro coculture model of monocyte-derived, cultured human dendritic cells (DC) with autologous CD4(+) resting T cells, CCR5 (R5)-tropic strains of HIV-1, but not CXCR4 (X4)-tropic strains, were transmitted to resting CD4+ T cells, leading to prolific viral output, although DC were susceptible to infection with either strain. Macrophages, which were also infectable with either R5- or X4-tropic strains, did not transmit infection to CD4+ cells. Highly productive HIV infection in this model appeared to be a consequence of heterokaryotic syncytium formation between infected DC and T cells since syncytia formation developed only in R5-infected DC/CD4+ cocultures. These results suggested that the unique microenvironment derived from the fusion between the infected DC and CD4+ cell was highly permissive and selective for replication of R5-tropic viruses. The apparent selectivity for R5-tropic strains in such syncytia was attributable neither to differential DC-mediated activation nor to selective modulation of induction of alpha- or beta-chemokines in the infected DC. This model of HIV replication may provide useful insights into in vitro correlates of HIV pathogenicity.
David
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SA
Merrell Dow Laboratory of Viral Pathogenesis Department of Microbiology, Immunology, and Molecular Genetics, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA. sdavid@kumc.edu
Smith
M S
MS
Lopez
G J
GJ
Adany
I
I
Mukherjee
S
S
Buch
S
S
Goodenow
M M
MM
Narayan
O
O
D015496:CD4-Positive T-Lymphocytes / Q000502:physiology / Q000821:virology*; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation; D009000:Monocytes / Q000821:virology; D019713:Receptors, CCR5 / Q000378:metabolism; D014779:Virus Replication
D018925:Chemokines; D019713:Receptors, CCR5