Virology. protein could not be detected either around the cell surface or in intracellular vesicles. The expanded tropism of the three strains shown here is therefore not due to adaptation to a new coreceptor but due to the capacity to exploit extremely low levels of CCR5 on Molt4 and SupT1 cells. This novel tropism observed for Finasteride acetate a subset of primary HIV-1 isolates may represent an extended tropism to new CD4+ cell types in vivo. CD4+ T cells and macrophages are important cell targets of human immunodeficiency computer virus (HIV) contamination. HIV strains have been classified into two main types: (i) syncytium-inducing (SI), T-cell line tropic (T-tropic), rapid/high strains and (ii) non-syncytium-inducing (NSI), macrophage-tropic (M-tropic), slow/low strains. In vitro, NSI viruses infect both macrophages and T-cell cultures but rarely T-cell lines. SI strains, however, replicate in a range of transformed CD4+ T-cell lines (31), while their capacity to infect macrophages is usually controversial (29, 38, 60, 66, 67, 81, 82). During primary acute infection, the majority of HIV type 1 (HIV-1) isolates are NSI (84), while SI strains emerge during disease progression in about 50% of AIDS patients (70). This emergence often precedes or coincides with a rapid decline in Finasteride acetate CD4+ cells in blood (41). Two receptors are required on the surface of the target cell to trigger HIV entry: the CD4 receptor and a coreceptor (22, 28, 30). Coreceptors have seven transmembrane domains (7TM) and are either members of or related to the chemokine receptor family. More than 10 7TM receptors have been shown to act as coreceptors for entry of different HIV-1 strains in vitro (reviewed in recommendations 4, 19, 26, and 47). All HIV-1 strains studied so far use either CCR5 or CXCR4 or both (67, Finasteride acetate 83). The discovery of HIV coreceptors has mainly explained the NSI/M-tropic Rabbit polyclonal to AIFM2 versus SI/T-tropic phenotype, by showing that this former strains use CCR5 (1, 17, 22, 27, 28), a receptor for CC chemokines RANTES, MIP-1, MIP-1, and MCP-2 (21, 33, 54, 58), while the latter use CXCR4 (30), a receptor for the CXC chemokine stromal cell-derived factor 1 (10, 50). A new nomenclature for HIV strains has been adopted, so that isolates that use CCR5 are termed R5 viruses, those using CXCR4 are designated X4 viruses, and viruses able to use both coreceptors are called R5X4 viruses (5). CCR5 is usually predominantly expressed on macrophages (53, 73, 79, 82), dendritic cells (3, 9, 34, 82), brain microglial cells (32, 36, 62), and memory T cells (11) but absent on most T-cell lines, while CXCR4 is usually more widely expressed and present on both naive and memory T cells (11, 46). Thus, the cellular tropism of different strains of HIV-1 is largely determined by differential usage of chemokine receptors. However, this simple picture has several exceptions. Hence, some CCR5-dependent HIV-1 strains do not infect macrophages, although they express high levels of CCR5 (14, 23). Moreover, particular primary CXCR4-using strains do not replicate in several cell lines that express high levels of CXCR4 (43). In this study, we show that while the majority of CCR5-using viruses do not infect T-cell lines, some strains (called Molt4/SupT1 strains) can infect the T-cell lines Molt4 and SupT1 (12). These strains include a molecularly cloned variant computer virus (C3) that was adapted in vitro for Molt4 replication and derived from JRCSF. A single amino acid change in the V1 loop accounts for C3s extended tropism for both Molt4 and SupT1 cells. The V3 loop on gp120 is usually a major determinant of both cell tropism (7, 15, 16, 37, 45, 61, 64, 72, 74) and more recently of coreceptor usage (8, 56, 68, 80). However, other envelope elements are also involved (39, 55, 56, 71), and several reports Finasteride acetate have implicated the V1 and V2 loops of gp120 (2, 12, 35, 40, 57, 69), which in addition to the required V3 domain influence the efficiency of replication of HIV-1 in primary macrophages (40, 63, 75) and in Jurkat T cells (13). Groenink et al. (35) described the configuration of a.