A trans-receptor mechanism for infection of CD4-negative cells by human immunodeficiency virus type 1

Chemokine receptors, particularly CCR5 and CXCR4, act as essential corecept ors 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 bee n encountered in Various tissues in vivo, including astrocytes, neurons and microvascular endothelial cells of the brain [2-6], 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 coreceptor s by well known HIV-1 strains when co-cultured with CD4(+) cells. This proc ess requires contact between the coreceptor-bearing and CD4(+) cells and su pports the full viral replication cycle within the coreceptor-bearing targe t cell. Furthermore, CD4 provided in trans facilitates infection of primary human cells, such as brain-derived astrocytes, Although the pathobiologica l significance of infection of CD4(-) cells in vivo remains to be elucidate d, this trans-receptor mechanism may facilitate generation of hidden reserv oirs of latent virus that confound antiviral therapies and that contribute to specific AIDS-associated clinical syndromes. (C) Elsevier Science Ltd IS SN 0960-9822.