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

  title={Identification of a major co-receptor for primary isolates of HIV-1},
  author={Hongkui Deng and Rong Liu and Wilfried Ellmeier and Sunny S Choe and Derya Unutmaz and Michael D. Burkhart and Paola Di Marzio and Shoshana Marmon and Richard E Sutton and C. Mark Hill and Craig B. Davis and Stephen C. Peiper and Thomas J. Schall and Dan R. Littman and Nathaniel R. Landau},
Entry of HIV-1 into target cells requires cell-surface CD4 and additional host cell cofactors. A cofactor required for infection with virus adapted for growth in transformed T-cell lines was recently identified and named fusin. However, fusin does not promote entry of macrophage-tropic viruses, which are believed to be the key pathogenic strains in vivo. The principal cofactor for entry mediated by the envelope glycoproteins of primary macrophage-tropic strains of HIV-1 is CC-CKR-5, a receptor… 

Co-receptors for HIV-1 entry.

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

A moving target: the multiple roles of CCR5 in infectious diseases.

  • R. Klein
  • Biology, Medicine
    The Journal of infectious diseases
  • 2008
The discovery of an HIV-resistant population who carried a 32-bp deletion within the coding sequence of CCR5 (CCR5A32) that results in a complete loss of function of the receptor in homozygous individuals remains the most important genetic factor associated with host resistance to HIV-1 infection.

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.

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.

Macrophage tropism of human immunodeficiency virus type 1 and utilization of the CC-CKR5 coreceptor

Using single-round replication-competent reporter viruses carrying the envelope genes of T-cell line- Tropic or macrophage-tropic phenotypic recombinant and mutant HIV-1 strains in infection of stable cell lines that coexpress the CD4 and chemokine receptors, a strict correlation between macrophages tropism and utilization of the CC-CKR5 receptor is unable to be established.

Adaptation of a CCR5-Using, Primary Human Immunodeficiency Virus Type 1 Isolate for CD4-Independent Replication

A major function of CD4 binding in the entry of primary HIV-1 isolates can be bypassed by changes in the gp120 V1-V2 elements, which allow the envelope glycoproteins to assume a conformation competent for CCR5 binding.

Expression pattern of HIV-1 coreceptors on T cells: implications for viral transmission and lymphocyte homing.

  • D. UnutmazD. Littman
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1997
The recent work follows up on studies performed during the last 6 years that had demonstrated the existence of distinct cellular tropisms of different strains of HIV-1 with similar tropism to those that emerge in transformed T cell lines.

Similarity of chemokines charge and the V3 domain of HIV-1 env protein.

This analysis shows that the chemokines corresponding to the different receptors have a similarly unbalanced composition of charged amino acids, and shows that SDF-1 appears to have the highest number of positive residues and the lowest number of negative residues, resulting in a net charge of +11.

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.



Identification of the envelope V3 loop as the primary determinant of cell tropism in HIV-1.

A 20-amino acid sequence from the macrophage-tropic BaL isolate of HIV-1 was sufficient to confermacrophage tropism on HTLV-IIIB, a T cell line--tropic isolate, and this small sequence element is in the V3 loop, the envelope domain that is the principal neutralizing determinant of HIV -1.

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

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 that is a putative G protein-coupled receptor with seven transmembrane segments.

Growth of macrophage-tropic and primary human immunodeficiency virus type 1 (HIV-1) isolates in a unique CD4+ T-cell clone (PM1): failure to downregulate CD4 and to interfere with cell-line-tropic HIV-1

Resistent with the lack of CD4 downregulation, persistent infection of PM1 by HIV-1BaL or HIV-2(573) failed to interfere with HIV-3IIIB superinfection, suggesting that a direct viral interaction may occur in vivo between biologically diverse HIV- 1 strains.

HIV-1 tropism for mononuclear phagocytes can be determined by regions of gp120 outside the CD4-binding domain

It is proposed that at least one determinant for mononuclear phagocyte tropism involves target cell interactions with regions of gp120 distinct from the CD4-binding domain, and genetic mapping of the macrophage-tropic phenotype by construction of recombinant viruses indicates this region can be determined by a 157-amino-acid region of the gp120 glycoprotein of HIV-1JR–FL.

Identification of RANTES, MIP-1α, and MIP-1β as the Major HIV-Suppressive Factors Produced by CD8+ T Cells

Recombinant human RANTES, Mip-1α, and MIP-1β induced a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV) and may have relevance for the prevention and therapy of AIDS.

Genotypic and phenotypic characterization of HIV-1 patients with primary infection.

In five HIV-1 seroconverters, the viral phenotype was found to be uniformly macrophage-tropic and non-syncytium-inducing and the viruses were genotypically homogeneous within each patient, but a common signature sequence was not discernible among transmitted viruses.

The viral envelope gene is involved in macrophage tropism of a human immunodeficiency virus type 1 strain isolated from brain tissue

Human immunodeficiency virus type 1 (HIV-1) strains isolated from the central nervous system (CNS) may represent a subgroup that displays a host cell tropism different from those isolated from

Identification of a determinant within the human immunodeficiency virus 1 surface envelope glycoprotein critical for productive infection of primary monocytes.

Alignment of the ADA sequence with published amino acid sequences of three additional monocytes-replicative and three monocyte-nonreplicative clones indicates 6 discrete residues with potential involvement in conferring productive human immunodeficiency virus 1 infection of primary monocytes.

The envelope glycoprotein of the human immunodeficiency virus binds to the immunoglobulin-like domain of CD4

These studies show that amino-acid residues within the amino-terminal immunoglobulin-like domain of human CD4 are involved in binding to gp120 as well as to many anti-CD4 monoclonal antibodies.

Vpr is required for efficient replication of human immunodeficiency virus type-1 in mononuclear phagocytes.

It is shown that vpr is important for efficient viral replication in primary monocyte/macrophages, but appears to play no role in activated or resting T cell infection, and a role for vpr molecules produced in newly infected cells is suggested, in addition to its presumed function in the virion.