HIV coreceptors, cell tropism and inhibition by chemokine receptor ligands

Abstract

HIV is a persistent virus that survives and replicates despite an onslaught by the host's immune system. A strategy for cell entry, requiring the use of two receptors, has evolved that may help evade neutralizing antibodies. HIV and SIV usually require both CD4 and a seven transmembrane (7TM) coreceptor for infection. At least eleven different 7TM coreceptors have been identified that confer HIV and/or SIV entry. For HIV-1, the major coreceptors are CCR5 and CXCR4, while the role of other coreceptors for replication and cell tropism in vivo is currently unclear. Polymorphisms in the CCR5 gene that reduce CCR5 expression levels, protect against disease progression, suggesting that drugs targeted to CCR5 could be effective. Such therapies however will not work if HIV simply adapts to use alternative coreceptors. In the light of these themes, this review will discuss the following topics: (i) the coreceptors used by primary HIV-1 and HIV-2 viruses, (ii) the properties and coreceptors of HIV-2 strains that infect cells without CD4, (iii) the role of coreceptors in HIV cell tropism and particularly macrophage infection and (iv) the properties of chemokine receptor ligands that block HIV infection.

Lentiviral transduction of human T-lymphocytes with a RANTES intrakine inhibits human immunodeficiency virus type 1 infection

“…Although CCR-5 is a major co-receptor for HIV infection, other chemokine receptors, such as CCR-3 and CCR-1, can also act as co-receptors. 2,4,8 Thus, down-regulation of multiple chemokine receptors might produce broader anti-HIV activities. Since RANTES binds promiscuously to CCR-1, CCR-3, and CCR-5, [22][23][24] we predicted that the …”

“…1,2 R5 (macrophage, M) tropic HIV-1 infects macrophages and primary CD4 + T cells mainly by using the CC-chemokine receptor 5 (CCR-5) as its principal co-receptor. [3][4][5][6][7][8] X4 (T cell line-tropic) HIV-1 strains infect CD4 + T cells primarily by using the co-receptor CXCR-4. Although other chemokine receptors can also participate in HIV-1 infection, CCR-5 has a critical role in both the initial infectious process and the progression of the disease.…”

“…Although other chemokine receptors can also participate in HIV-1 infection, CCR-5 has a critical role in both the initial infectious process and the progression of the disease. 1,2,8 It is used by almost all Mtropic HIV-1 strains, regardless of their viral genetic subtype, and by the related lentiviruses HIV-2 and simian immunodeficiency virus (SIV). 1,2 Persons with a homozygous 32 base-pair deletion in the CCR-5 gene, resulting in a truncated protein that remains within the cell, are highly resistant to HIV-1 infection.…”

RANTES Binding and Down-Regulation by a Novel Human Herpesvirus-6 β Chemokine Receptor

“…6). Expression of the CC chemokines RANTES, macrophage inflammatory protein-1␣ (MIP-1␣) and MIP-1␤ contribute to the resistance of CD4 ϩ T cells from HIV-exposed-uninfected individuals to HIV infection, and mutations in both chemokine receptor and chemokine genes have been shown to confer resistance to HIV infection.…”

Identification of Shared Populations of Human Immunodeficiency Virus Type 1 Infecting Microglia and Tissue Macrophages outside the Central Nervous System

“…The cellular tropism of human immunodeficiency virus type 1 (HIV-1) is governed at a variety of entry and postentry steps, including the attachment, fusion, and entry of HIV into the cell, reverse transcription, integration, and gene expression (16,31,39). Differences between CD4 lymphocytes, the principal targets of HIV-1 in vivo, and other potential cellular targets for HIV-1, such as macrophages and microglia in the brain, exist at many of these levels, particularly in the expression of CD4 and chemokine coreceptors required for virus entry.…”