Faculty Opinions recommendation of Death of CD4(+) T-cell lines caused by human immunodeficiency virus type 1 does not depend on caspases or apoptosis.

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) non-syncytium-inducing (NSI) strains predominantly use the chemokine receptor CCR5, while syncytium-inducing (SI) strains use CXCR4. In vitro, SI isolates infect and replicate in a range of CD4+ CXCR4+ T-cell lines, whereas NSI isolates usually do not. Here we describe three NSI strains that are able to infect two CD4+ T-cell lines, Molt4 and SupT1. For one strain, a variant of JRCSF selected in vitro, replication on Molt4 was previously shown to be conferred by a single amino-acid change in the V1 loop (M.T. Boyd et al., J. Virol. 67:3649–3652, 1993). On CD4+ cell lines expressing different coreceptors, these strains use CCR5 predominantly and do not replicate in CCR5-negative peripheral blood mononuclear cells derived from individuals homozygous for Δ32 CCR5. Furthermore, infection of Molt4 and SupT1 by each of these three strains is potently inhibited by ligands for CCR5, including 2D7, a monoclonal antibody specific for CCR5. CCR5 mRNA was present in both Molt4 and SupT1 by reverse transcription-PCR, although CCR5 protein could not be detected either on 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 a subset of primary HIV-1 isolates may represent an extended tropism to new CD4+ cell types in vivo.

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Herpesvirus saimiri-encoded proteins Tip and StpC modulate human immunodeficiency virus type 1 replication in T-cell lines and lymphocytes independently of viral tropism

Virology ◽

10.1016/j.virol.2004.03.021 ◽

2004 ◽

Vol 324 (1) ◽

pp. 60-66 ◽

Cited By ~ 5

Author(s):

Andrea D Raymond ◽

Muneer G Hasham ◽

Alexander Y Tsygankov ◽

Earl E Henderson

Keyword(s):

Human Immunodeficiency Virus ◽

T Cell ◽

Cell Lines ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Herpesvirus Saimiri ◽

Viral Tropism ◽

Immunodeficiency Virus ◽

T Cell Lines

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Role of CXCR4 in Cell-Cell Fusion and Infection of Monocyte-Derived Macrophages by Primary Human Immunodeficiency Virus Type 1 (HIV-1) Strains: Two Distinct Mechanisms of HIV-1 Dual Tropism

Journal of Virology ◽

10.1128/jvi.73.9.7117-7125.1999 ◽

1999 ◽

Vol 73 (9) ◽

pp. 7117-7125 ◽

Cited By ~ 69

Author(s):

Yanjie Yi ◽

Stuart N. Isaacs ◽

Darlisha A. Williams ◽

Ian Frank ◽

Dominique Schols ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

T Cell ◽

Cell Lines ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Wild Type ◽

Immunodeficiency Virus ◽

T Cell Lines ◽

Hiv 1

ABSTRACT Dual-tropic human immunodeficiency virus type 1 (HIV-1) strains infect both primary macrophages and transformed T-cell lines. Prototype T-cell line-tropic (T-tropic) strains use CXCR4 as their principal entry coreceptor (X4 strains), while macrophagetropic (M-tropic) strains use CCR5 (R5 strains). Prototype dual tropic strains use both coreceptors (R5X4 strains). Recently, CXCR4 expressed on macrophages was found to support infection by certain HIV-1 isolates, including the dual-tropic R5X4 strain 89.6, but not by T-tropic X4 prototypes like 3B. To better understand the cellular basis for dual tropism, we analyzed the macrophage coreceptors used for Env-mediated cell-cell fusion as well as infection by several dual-tropic HIV-1 isolates. Like 89.6, the R5X4 strain DH12 fused with and infected both wild-type and CCR5-negative macrophages. The CXCR4-specific inhibitor AMD3100 blocked DH12 fusion and infection in macrophages that lacked CCR5 but not in wild-type macrophages. This finding indicates two independent entry pathways in macrophages for DH12, CCR5 and CXCR4. Three primary isolates that use CXCR4 but not CCR5 (tybe, UG021, and UG024) replicated efficiently in macrophages regardless of whether CCR5 was present, and AMD3100 blocking of CXCR4 prevented infection in both CCR5 negative and wild-type macrophages. Fusion mediated by UG021 and UG024 Envs in both wild-type and CCR5-deficient macrophages was also blocked by AMD3100. Therefore, these isolates use CXCR4 exclusively for entry into macrophages. These results confirm that macrophage CXCR4 can be used for fusion and infection by primary HIV-1 isolates and indicate that CXCR4 may be the sole macrophage coreceptor for some strains. Thus, dual tropism can result from two distinct mechanisms: utilization of both CCR5 and CXCR4 on macrophages and T-cell lines, respectively (dual-tropic R5X4), or the ability to efficiently utilize CXCR4 on both macrophages and T-cell lines (dual-tropic X4).

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