Definition of the range and distribution of human immunodeficiency virus macrophage tropism using PCR-based infectivity measurements

Collin, Matthew; Illei, Peter B.; James, William; Gordon, Siamon

doi:10.1099/0022-1317-75-7-1597

Cited by 24 publications

(11 citation statements)

References 39 publications

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“…Following the completion of DNA synthesis, the RTC matures in the PIC. The double-stranded viral DNA is synthesised within a few hours in T cells but is slower (36 to 48 h) in macrophages, for unknown reasons (Collin et al, 1994;O'Brien et al, 1994). RTCs migrate towards the nucleus, probably by using cellular motors, such as dynein, to move along the cell cytoskeleton (Bukrinskaya et al, 1998;McDonald et al, 2002).…”

Section: Nuclear Importmentioning

confidence: 99%

Macrophages and HIV-1: dangerous liaisons

Verani¹,

Gras

Pancino

2005

Molecular Immunology

100

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Section: Nuclear Importmentioning

confidence: 99%

Macrophages and HIV-1: dangerous liaisons

Verani¹,

Gras

Pancino

2005

Molecular Immunology

100

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“…2C). The gp120s of these two strains are only 84% identical, and they show differences in the degree of their macrophage tropism (11). Therefore, the ability of at least five aptamers to neutralize at least two HIV-1 strains suggests that they might recognize functionally important sites on gp120 that are conserved between at least the R5 members of this clade B subtype.…”

Section: Neutralization Of Subtype B R5 Strains Of Hiv-1 By Aptamersmentioning

confidence: 99%

Neutralization of Infectivity of Diverse R5 Clinical Isolates of Human Immunodeficiency Virus Type 1 by gp120-Binding 2′F-RNA Aptamers

Khati

Schüman

Ibrahim

et al. 2003

J Virol

163

157

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Human immunodeficiency virus type 1 (HIV-1) has evolved a number of strategies to resist current antiretroviral drugs and the selection pressures of humoral and cellular adaptive immunity. For example, R5 strains, which use the CCR5 coreceptor for entry and are the dominant viral phenotype for HIV-1 transmission and AIDS pathogenesis, are relatively resistant to neutralization by antibodies, as are other clinical isolates. In order to overcome these adaptations, we raised nucleic acid aptamers to the SU glycoprotein (gp120) of the R5 strain, HIV-1 Ba-L . These not only bound gp120 with high affinity but also neutralized HIV-1 infectivity in human peripheral blood mononuclear cells (PBMCs) by more than 1,000-fold. Furthermore, these aptamers were able to neutralize the infectivity of R5 clinical isolates of HIV-1 derived from group M (subtypes A, C, D, E, and F) and group O. One aptamer defined a site on gp120 that overlaps partially with the conserved, chemokine receptor-binding, CD4-induced epitope recognized by monoclonal antibody 17b. In contrast to the antibody, the site is accessible to aptamer in the absence of CD4 binding. Neutralizing aptamers such as this could be exploited to provide leads in developing alternative, efficacious anti-HIV-1 drugs and lead to a deeper understanding of the molecular interactions between the virus and its host cell.While current antiretroviral drugs have prolonged the quality of life for many human immunodeficiency virus type 1 (HIV-1)-positive individuals, they do not eliminate the virus (15, 37). The rapid emergence of drug-resistant HIV-1 strains has encouraged continued efforts to find novel antiretroviral agents with modalities different from those currently in use. One approach is to target the stage at which virus infects host cells. The entry of HIV-1 into target cells, its cellular tropism, and elements of the pathogenesis of AIDS are largely determined by the virion surface glycoprotein, gp120 (8,9,30). Variation in the hypervariable loops of gp120, particularly the V3 loop, determines the cellular tropism of the virus by governing the interaction with chemokine receptors such as CCR5 and CXCR4 (E. A. Berger, R. W. Doms et al., Letter, Nature 391:240, 1998). Strains that infect via CCR5, known as R5 strains, are preferentially transmitted from host to host (41), dominate the asymptomatic stage of infection (18,36), and are sufficient to cause AIDS (33).Elucidation of the three-dimensional crystal structure of gp120 (26, 27) coupled with site-directed mutagenesis (12, 24, 40) has revealed the remarkable way in which HIV-1 has evolved to protect its functionally conserved regions, thereby evading host antibody responses (26, 27). For example, regions of gp120 that interact with coreceptors are masked by extensive glycosylation and surface loops, limiting the ability of the immune system to mount a broad-spectrum neutralizing antibody response. These features partly explain the failure of candidate vaccine antigens based on recombinant HIV-1 surface envelope glycopro...

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“…CCR5, the most commonly used coreceptor, is present on primary T cells and macrophages. In contrast, CXCR4 is expressed on many cell types, including thymocytes, primary T cells, and macrophages (13). CXCR4-using viruses can induce formation of syncytia when cultured on the CXCR4-bearing MT2 cell line (syncytiuminducing, SI viruses) (3,8,21,33,48).…”

mentioning

confidence: 99%

Coreceptor Tropism in Human Immunodeficiency Virus Type 1 Subtype D: High Prevalence of CXCR4 Tropism and Heterogeneous Composition of Viral Populations

Huang¹,

Eshleman

Toma³

et al. 2007

J Virol

146

139

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In human immunodeficiency virus type 1 (HIV-1) subtype B, CXCR4 coreceptor use ranges from ϳ20% in early infection to ϳ50% in advanced disease. Coreceptor use by non-subtype B HIV is less well characterized. We studied coreceptor tropism of subtype A and D HIV-1 collected from 68 pregnant, antiretroviral drug-naive Ugandan women (HIVNET 012 trial). None of 33 subtype A or 10 A/D-recombinant viruses used the CXCR4 coreceptor. In contrast, nine (36%) of 25 subtype D viruses used both CXCR4 and CCR5 coreceptors. Clonal analyses of the nine subtype D samples with dual or mixed tropism revealed heterogeneous viral populations comprised of X4-, R5-, and dual-tropic HIV-1 variants. In five of the six samples with dual-tropic strains, V3 loop sequences of dual-tropic clones were identical to those of cocirculating R5-tropic clones, indicating the presence of CXCR4 tropism determinants outside of the V3 loop. These dual-tropic variants with R5-tropic-like V3 loops, which we designated "dual-R," use CCR5 much more efficiently than CXCR4, in contrast to dual-tropic clones with X4-tropic-like V3 loops ("dual-X"). These observations have implications for pathogenesis and treatment of subtype D-infected individuals, for the association between V3 sequence and coreceptor tropism phenotype, and for understanding potential mechanisms of evolution from exclusive CCR5 use to efficient CXCR4 use by subtype D HIV-1.Human immunodeficiency virus type 1 (HIV-1) infection requires interactions between the viral envelope (Env) surface glycoprotein (gp120), the cellular receptor (CD4), and a coreceptor (e.g., CCR5 and/or CXCR4) (36). CCR5, the most commonly used coreceptor, is present on primary T cells and macrophages. In contrast, CXCR4 is expressed on many cell types, including thymocytes, primary T cells, and macrophages (13). CXCR4-using viruses can induce formation of syncytia when cultured on the CXCR4-bearing MT2 cell line (syncytiuminducing, SI viruses) (3,8,21,33,48). SI or CXCR4-using viruses are typically found in individuals with advanced disease (2,9,16,18,19). However, it is not clear whether CXCR4 use precedes and causes more rapid disease progression or is merely the consequence of a change in target cell availability. The recent development of HIV-1 entry inhibitors that target CCR5 has heightened interest in coreceptor usage (44).Several surveys of coreceptor tropism were reported recently. Brumme et al. (6) studied almost 1,000 antiretroviral drug naive HIV-1-infected patients. CXCR4-using virus was detected in 18% of those individuals, more than 99% of which were also able to use CCR5 and were thus categorized as dualor mixed-tropic (DM). CXCR4 use was associated with decreased survival in univariate, but not multivariate, analyses. There was a statistically nonsignificant trend toward increased CXCR4 use in non-subtype B viruses (7 of 13 [54%] for nonsubtype B versus 143 of 675 [21%] for subtype B; C. J. Brumme and P. R. Harrigan, unpublished data). Moyle et al. (37) evaluated predictive factors for coreceptor use am...

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Definition of the range and distribution of human immunodeficiency virus macrophage tropism using PCR-based infectivity measurements

Cited by 24 publications

References 39 publications

Macrophages and HIV-1: dangerous liaisons

Macrophages and HIV-1: dangerous liaisons

Neutralization of Infectivity of Diverse R5 Clinical Isolates of Human Immunodeficiency Virus Type 1 by gp120-Binding 2′F-RNA Aptamers

Coreceptor Tropism in Human Immunodeficiency Virus Type 1 Subtype D: High Prevalence of CXCR4 Tropism and Heterogeneous Composition of Viral Populations

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