title: A trans-receptor mechanism for infection of CD4-negative cells by human immunodeficiency virus type 1.
abstract: Chemokine receptors, particularly CCR5 and CXCR4, act as essential coreceptors in concert with CD4 for cellular entry by human immunodeficiency virus type 1 (HIV-1; reviewed in [1]). But infection of CD4(-) cells has also been encountered in various tissues in vivo, including astrocytes, neurons and microvascular endothelial cells of the brain [2] [3] [4] [5] [6], epithelial cells [5] [7], CD4(-) lymphocytes and thymocytes [8] [9], and cardiomyocytes [10]. Here, we present evidence for the infection of CD4(-) cell lines bearing coreceptors by well-known HIV-1 strains when co-cultured with CD4(+) cells. This process requires contact between the coreceptor-bearing and CD4(+) cells and supports the full viral replication cycle within the coreceptor-bearing target cell. Furthermore, CD4 provided in trans facilitates infection of primary human cells, such as brain-derived astrocytes. Although the pathobiological significance of infection of CD4(-) cells in vivo remains to be elucidated, this trans-receptor mechanism may facilitate generation of hidden reservoirs of latent virus that confound antiviral therapies and that contribute to specific AIDS-associated clinical syndromes.
authors.affiliation: Gladstone Institute of Virology and Immunology, PO Box 419100, San Francisco, California 94141, USA.
authors.forename: R F
authors.initials: RF
authors.lastname: Speck
authors.forename: U
authors.initials: U
authors.lastname: Esser
authors.forename: M L
authors.initials: ML
authors.lastname: Penn
authors.forename: D A
authors.initials: DA
authors.lastname: Eckstein
authors.forename: L
authors.initials: L
authors.lastname: Pulliam
authors.forename: S Y
authors.initials: SY
authors.lastname: Chan
authors.forename: M A
authors.initials: MA
authors.lastname: Goldsmith
mesh_terms: D015704:CD4 Antigens / Q000032:analysis*; D002460:Cell Line; D002469:Cell Separation; D005434:Flow Cytometry; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008561:Membrane Fusion / Q000502:physiology*; D015728:Receptors, HIV / Q000502:physiology*
chemical_list: D015704:CD4 Antigens; D015728:Receptors, HIV