The role of dendritic cells in the infection of CD4+ T cells with the human immunodeficiency virus: use of dendritic cells from individuals homozygous for the delta32CCR5 allele as a model.
Despite exposure to multiple strains of both macrophage (M)-tropic and T cell (T)-tropic HIV, primary infection is largely restricted to relatively homogeneous M-tropic virus. Since dendritic cells (DCs) play a pivotal role in the early events of HIV infection, several studies have focused on the role of DCs in this restriction. It has been proposed that DCs are more efficiently infected with M-tropic versus T-tropic viruses; however, the infectability of DCs and the relevance of their infectability for inducing productive infection is controversial. It has also been suggested that variability in DC expression of coreceptors for M-tropic versus T-tropic virus could explain the restriction in the transmitting virus. Using HIV-pulsed DCs from individuals with a homozygous deletion in the CCR5 gene as a human "knockout" model, we demonstrate that infection of DCs per se is not necessary to promulgate infection in CD4+ T cells. The data also suggest that transmission of HIV to CD4+ T cells is not dependent on DC coreceptor expression.
Dybul
M
M
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Weissman
D
D
Rubbert
A
A
Machado
E
E
Cohn
M
M
Ehler
L
L
O'Callahan
M
M
Mizell
S
S
Fauci
A S
AS
D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D003713:Dendritic Cells / Q000378:metabolism / Q000821:virology*; D006678:HIV / Q000502:physiology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D006720:Homozygote; D006801:Humans; D008264:Macrophages / Q000821:virology; D019713:Receptors, CCR5 / Q000096:biosynthesis / Q000235:genetics*; D014779:Virus Replication
D019713:Receptors, CCR5