HIV-1 Entry Cofactor: Functional cDNA Cloning of a Seven-Transmembrane, G Protein-Coupled Receptor

  title={HIV-1 Entry Cofactor: Functional cDNA Cloning of a Seven-Transmembrane, G Protein-Coupled Receptor},
  author={Yu Feng and Christopher C. Broder and Paul E. Kennedy and Edward A Berger},
  pages={872 - 877}
A cofactor for HIV-1 (human immunodeficiency virus-type 1) fusion and entry was identified with the use of a novel functional complementary DNA (cDNA) cloning strategy. This protein, designated “fusin,” is a putative G protein-coupled receptor with seven transmembrane segments. Recombinant fusin enabled CD4-expressing nonhuman cell types to support HIV-1 Env-mediated cell fusion and HIV-1 infection. Antibodies to fusin blocked cell fusion and infection with normal CD4-positive human target… 

Chemokine receptors as fusion cofactors for human immunodeficiency virus type 1 (HIV-1)

The discovery of distinct chemokine receptors that support entry of T-cell tropic (CXCR-4) and macrophage tropic HIV-1 strains (CCR-5) explains the differences in cell tropism between viral strains, the inability of HIV- 1 to infect most nonprimate cells, and the resistance of a small percentage of the population to HIV-2 infection.

Identification of a major co-receptor for primary isolates of HIV-1

The principal cofactor for entry mediated by the envelope glycoproteins of primary macrophage-tropic strains of HIV-1 is CC-CKR-5, a receptor for the β-chemokines RANTES, Mip-1α and MIP-1β.

HIV-1 Entry and Membrane Fusion Inhibitors

The structural biology of HIV-1 Env and its complexes with the cellular receptors has provided a structural basis for the rational design of fusion inhibitors as potential antiviral therapeutics and related therapeutic strategies to block viral entry are discussed.

HIV-1 envelope determinants for cell tropism and chemokine receptor use.

The discovery that Env initially binds the CD4 molecule on the target cell surface and then makes subsequent interactions with one of several members of the chemokine receptor family has greatly enhanced the molecular understanding of HIV-1 entry.

Selective employment of chemokine receptors as human immunodeficiency virus type 1 coreceptors determined by individual amino acids within the envelope V3 loop

It is demonstrated that the specific amino acids in the V3 loop of the HIV-1 envelope protein that determine cellular tropism also regulate chemokine coreceptor preference for cell entry by the virus.

An Inducible Cell-Cell Fusion System with Integrated Ability to Measure the Efficiency and Specificity of HIV-1 Entry Inhibitors

A cell-cell fusion system capable of simultaneously monitoring inhibition efficiency and specificity and suitable for large-scale screening of chemical libraries and can be used for detailed characterization of inhibitory and cytotoxic properties of known entry inhibitors.

Expression cloning of new receptors used by simian and human immunodeficiency viruses

Two members of the seven-transmembrane G-protein-coupled receptor family that are used not only by SIVs, but also by strains of HIV-2 and M-tropic HIV-1 are identified.

Identification of a chemokine receptor encoded by human cytomegalovirus as a cofactor for HIV-1 entry.

The human cytomegalovirus encodes a beta-chemokine receptor (US28) that is distantly related to the human chemokine receptors CCR5 and CXCR4, which also serve as cofactors for the entry into cells of

Replication-Competent Rhabdoviruses with Human Immunodeficiency Virus Type 1 Coats and Green Fluorescent Protein: Entry by a pH-Independent Pathway

A replication-competent, recombinant vesicular stomatitis virus in which the gene encoding the single transmembrane glycoprotein (G) was deleted and replaced by anenv-G hybrid gene encoding a green fluorescent protein added to permit rapid detection of infection.



Cofactor requirement for human immunodeficiency virus type 1 entry into a CD4-expressing human cell line

Results suggest that HeLa cells express a factor(s) that can complement the viral entry defect of U373-CD4 cells and is necessary for efficient CD4-mediated HIV-1 infection.

Fusogenic selectivity of the envelope glycoprotein is a major determinant of human immunodeficiency virus type 1 tropism for CD4+ T-cell lines vs. primary macrophages.

  • C. BroderE. Berger
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1995
It is concluded that the intrinsic fusion selectivity of env plays a major role in the tropism of a HIV-1 isolate for infection of CD4+ T-cell lines vs. primary macrophages, presumably by determining the selectivityof virus entry and cell fusion.

Human genes other than CD4 facilitate HIV-1 infection of murine cells.

It is demonstrated that there are at least two different restrictions to infectivity on the mouse background which can be complemented by the human genome, and mapping studies suggest that fewer than five human chromosomes are necessary for reconstituting infectivity in the murine background.

Proteinase-resistant factors in human erythrocyte membranes mediate CD4-dependent fusion with cells expressing human immunodeficiency virus type 1 envelope glycoproteins

The role of human-specific factors in Env/CD4-mediated fusion is shown by the ability of transient cell hybrids formed between CD4+ murine cells and human HeLa cells to fuse with Env+ cells.

Replication of HIV type 1 in rabbit cell lines is not limited by deficiencies in tat, rev, or long terminal repeat function.

Examination of viral RNA production indicated that the major HIV transcripts were produced in HIV-infected rabbit cells, but were present at levels significantly lower than those found for human cells.

The block to HIV-1 envelope glycoprotein-mediated membrane fusion in animal cells expressing human CD4 can be overcome by a human cell component(s).

Results indicate that the fusion block is not due to dominant inhibitory components in the animal cell and suggest that human cells contain an additional component(s) which, when transferred to the CD4-bearing animal cell, confers the ability to undergo membrane fusion mediated by the HIV-1 envelope glycoprotein.

Different requirements for membrane fusion mediated by the envelopes of human immunodeficiency virus types 1 and 2

This block in CD4+ cells derived from the human cell lines U87MG and SCL1 cannot be infected by human immunodeficiency virus type 1 (HIV-1) or fuse with cells expressing the HIV-1 envelope and probably reflects the absence of cellular factors necessary for membrane fusion.

Fusogenic mechanisms of enveloped-virus glycoproteins analyzed by a novel recombinant vaccinia virus-based assay quantitating cell fusion-dependent reporter gene activation

Cell fusion dependence was demonstrated by the strict requirement for both CD4 and functional Env expression and by the inhibitory effects of known fusion-blocking monoclonal antibodies and pharmacological agents, suggesting that the fusion deficiency with nonhuman cells was not associated with irreversible defects in CD4.

Selective infection of human CD4+ cells by simian immunodeficiency virus: productive infection associated with envelope glycoprotein-induced fusion.

  • S. KoenigV. Hirsch P. Johnson
  • Biology, Medicine
    Proceedings of the National Academy of Sciences of the United States of America
  • 1989
It is demonstrated that SIV had a restricted host range among human CD4+ cells when compared with human immunodeficiency virus type 1 or type 2 and that additional envelope-cell interactions after CD4 binding are required for productive infection.